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Cognitive Impairment

381 studies in the atlas

Cognitive dysfunction — commonly described as brain fog — is one of the most disabling and frequently reported symptoms of ME/CFS. It affects memory, concentration, word retrieval, and processing speed. Cognitive exertion can trigger PEM, making sustained mental activity dangerous for many patients.

What we know

  • Cognitive dysfunction is reported by a majority of ME/CFS patients and significantly impacts daily functioning
  • Reduced cerebral blood flow during upright posture may contribute to cognitive symptoms
  • Cognitive exertion can trigger PEM, sometimes as reliably as physical exertion
  • Neuropsychological testing shows measurable deficits in processing speed and attention in some studies

What remains uncertain

  • Whether cognitive impairment is driven primarily by reduced cerebral blood flow, neuroinflammation, or metabolic factors
  • The relationship between subjective cognitive complaints and objective neuropsychological test performance varies across studies
  • Whether cognitive symptoms fluctuate in parallel with other ME/CFS symptoms or have independent drivers
  • Sleep disruption may contribute to cognitive dysfunction, but the direction of causation is unclear

What is emerging

  • Whether cognitive rehabilitation approaches adapted for ME/CFS (respecting PEM thresholds) can help
  • The neurobiological basis of brain fog at the cellular level
  • Whether cognitive biomarkers can track disease progression
  • The relationship between cognitive impairment and neuroinflammatory findings

Start here

E0 ConsensusPEM requiredModerate confidence

Myalgic encephalomyelitis/chronic fatigue syndrome and fibromyalgia - overlap, differences, and emerging insights.

Murovska, Modra, Krumina, Angelika, Araja, Diana et al.·Journal of translational medicine·2026

ME/CFS and fibromyalgia are two different but often overlapping illnesses that cause severe fatigue, pain, and other debilitating symptoms. While they share many similarities, ME/CFS has a distinctive feature called post-exertional malaise—where activity makes symptoms dramatically worse for hours or days—while fibromyalgia does not. This review shows that the two conditions have different immune system patterns and may require different treatment approaches.

Research Momentum

381 publications over 37 years. Recent trend: steady (17/year over the last 3 years).

All Studies

381 studies, sorted by review status and evidence level

E0 ConsensusPEM unclearModerate confidenceSystematic-ReviewEditor reviewed

Evaluating working memory functioning in individuals with myalgic encephalomyelitis/chronic fatigue syndrome: a systematic review and meta-analysis.

Penson, Maddison, Kelly, Kate·Psychology, health & medicine·2026

This study reviewed 34 research papers to understand how ME/CFS affects working memory—the ability to hold and use information in your mind briefly. The researchers found that people with ME/CFS have significant difficulties with verbal working memory (remembering words and language), but their ability to remember visual information (like images or patterns) appeared similar to people without ME/CFS. This suggests that cognitive problems in ME/CFS may affect certain types of thinking more than others.

Cognitive Impairment
E0 ConsensusPEM not requiredModerate confidenceReview-NarrativeEditor reviewed

[Cognitive impairment in asthenic disorders].

Chutko, L S, Surushkina, S Yu, Yakovenko, E A et al.·Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova·2025

This review examined research on how chronic fatigue syndrome and related conditions affect thinking and mental processing abilities. The authors looked at different theories about what causes these disorders and found that problems with cognitive control—the brain's ability to focus, plan, and manage mental tasks—may play an important role in how these conditions develop and persist.

Cognitive Impairment
E0 ConsensusPEM requiredModerate confidenceReview-NarrativeEditor reviewed

Chronic Fatigue Syndrome: Diagnosis, Treatment, and Future Direction.

Graves, B Sue, Patel, Mitsu, Newgent, Hailey et al.·Cureus·2024

ME/CFS is a serious illness that causes extreme tiredness that doesn't improve with rest and often gets worse with activity. People with ME/CFS also struggle with brain fog, pain, sleep problems, and immune system issues. Right now, doctors don't have a simple blood test or scan to diagnose ME/CFS, which makes it hard to identify and treat the condition properly.

BiomarkersImmune SystemCognitive ImpairmentPost-Exertional Malaise
E0 ConsensusPEM not requiredModerate confidenceReview-NarrativeEditor reviewed

[Chronic fatigue syndrome in children].

Chutko, L S, Surushkina, S Yu, Yakovenko, E A et al.·Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova·2024

This article reviews existing research on ME/CFS (chronic fatigue syndrome) in children. The authors summarize what scientists have learned about how common the condition is, what causes it, how doctors diagnose it, and what treatments might help. A major focus is on cognitive problems—like difficulty concentrating and brain fog—that children with ME/CFS often experience.

Cognitive Impairment
E0 ConsensusPEM not requiredHigher confidenceEditor reviewed

Systematic review and meta-analysis of cognitive impairment in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Aoun Sebaiti, Mehdi, Hainselin, Mathieu, Gounden, Yannick et al.·Scientific reports·2022

This large review examined research on thinking and memory problems in ME/CFS by looking at 764 studies published over 30 years. The researchers found that people with ME/CFS commonly experience difficulties with memory (especially visual and verbal memory), processing speed when reading, and attention, but their problem-solving and basic mental functions are usually preserved. The study shows that cognitive problems in ME/CFS are real and measurable, though they vary from person to person.

Cognitive Impairment
E0 ConsensusPEM not requiredPreliminaryReview-NarrativeEditor reviewed

Stabilometric Biofeedback Training in Cognitive and Affective Function Improvement. Contribution of the Russian Scientific School. Part II.

Bazanova, O M, Kovaleva, A V·Human physiology·2022

This review examines how balance training using computer feedback can help improve thinking, mood, and symptom management in people with chronic fatigue syndrome and other neurological conditions. The researchers looked at studies from Russia and other countries that used a technique called stabilometric biofeedback, which shows patients real-time information about their body's balance and posture to help them improve control and function.

Cognitive Impairment
E0 ConsensusPEM unclearPreliminaryReview-NarrativeEditor reviewed

The Gut Microbiome in Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS).

König, Rahel S, Albrich, Werner C, Kahlert, Christian R et al.·Frontiers in immunology·2021

This review examines whether changes in gut bacteria might contribute to ME/CFS. The authors suggest that lifetime antibiotic use could alter the balance of gut microbes, which might then affect the gut barrier, brain function, and energy production in cells. They propose several potential treatment approaches like probiotics and dietary changes, but emphasize that much more research is needed to understand if gut bacteria actually cause ME/CFS or simply change as a result of the disease.

Cognitive Impairment
E0 ConsensusPEM requiredHigher confidenceSystematic-ReviewEditor reviewed

Review of case definitions for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Lim, Eun-Jin, Son, Chang-Gue·Journal of translational medicine·2020

This study reviewed how ME/CFS has been defined and diagnosed over the past 34 years, examining 25 different case definitions created by researchers. The researchers found that these definitions fall into four main categories and emphasize different key symptoms—some focus on a viral cause, others on inflammation, and some on multiple system problems. Understanding these different approaches helps doctors and patients recognize that ME/CFS is complex and may require more than one way to diagnose it.

Cognitive ImpairmentPost-Exertional Malaise
E0 ConsensusPEM unclearModerate confidenceSystematic-ReviewEditor reviewed

A systematic review of neurological impairments in myalgic encephalomyelitis/ chronic fatigue syndrome using neuroimaging techniques.

Maksoud, Rebekah, du Preez, Stanley, Eaton-Fitch, Natalie et al.·PloS one·2020

This review examined 55 studies that used brain imaging techniques to look for physical differences in the brains of people with ME/CFS compared to healthy people. The researchers found evidence that ME/CFS affects how the nervous system works, including changes in brain structure and blood flow. However, the findings weren't consistent across all studies, meaning scientists still don't have a complete picture of what's happening in the brain.

Autonomic Nervous SystemCognitive Impairment
E0 ConsensusPEM requiredModerate confidenceReview-NarrativeEditor reviewed

[Neurologic Abnormalities in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Review].

Komaroff, Anthony L, Takahashi, Ryosuke, Yamamura, Takashi et al.·Brain and nerve = Shinkei kenkyu no shinpo·2018

This review examines objective, measurable evidence that ME/CFS is a real physical illness, not just a psychological condition. Researchers looked at studies showing that ME/CFS involves problems with the brain, immune system, and how the body uses energy. They found that immune activation—where the body's defense system becomes overactive—may be a key driver of ME/CFS symptoms.

Immune SystemCognitive ImpairmentPost-Exertional Malaise
E0 ConsensusPEM not requiredModerate confidenceSystematic-ReviewEditor reviewed

Attentional and interpretive bias towards illness-related information in chronic fatigue syndrome: A systematic review.

Hughes, Alicia, Hirsch, Colette, Chalder, Trudie et al.·British journal of health psychology·2016

This review looked at research studies examining how people with ME/CFS pay attention to and interpret information about illness and symptoms. The studies found that some people with ME/CFS tend to notice health-related threats more quickly and interpret their body sensations as signs of illness more readily than healthy people do. These thinking patterns may help keep the fatigue and illness beliefs going, even when other factors aren't actively causing symptoms.

Cognitive Impairment
E0 ConsensusPEM not requiredHigher confidenceMeta-AnalysisEditor reviewed

Cognitive functioning in chronic fatigue syndrome: a meta-analysis.

Cockshell, S J, Mathias, J L·Psychological medicine·2010

This study combined results from 50 research papers to understand how ME/CFS affects thinking and memory. Researchers found that people with ME/CFS have real, measurable problems with attention, memory, and processing speed—essentially, the brain takes longer to handle and organize information. However, other thinking skills like vocabulary, reasoning, and basic motor skills were not affected.

Cognitive Impairment
E0 ConsensusPEM not requiredModerate confidenceReview-NarrativeEditor reviewed

Evidence-based efficacy of adaptogens in fatigue, and molecular mechanisms related to their stress-protective activity.

Panossian, Alexander, Wikman, Georg·Current clinical pharmacology·2009

This review examined whether herbal supplements called adaptogens can help with fatigue and ME/CFS. Researchers found that some adaptogens—particularly Rhodiola rosea—showed promise in clinical studies for improving attention, thinking, and mental energy in people with fatigue and chronic fatigue syndrome. The review suggests these herbs may work by helping the body manage stress through changes in specific stress-response proteins and hormones.

Cognitive Impairment
E0 ConsensusPEM not requiredModerate confidenceReview-NarrativeEditor reviewed

Neuropsychological functioning in chronic fatigue syndrome: a review.

Michiels, V, Cluydts, R·Acta psychiatrica Scandinavica·2001

This review looked at studies examining thinking and memory problems in ME/CFS patients. Researchers found that people with ME/CFS commonly experience slower thinking speed, difficulty holding information in working memory, and trouble learning new information. The study noted that brain scans haven't shown a consistent pattern that uniquely identifies ME/CFS patients, and that fatigue severity doesn't fully explain the cognitive problems.

Cognitive Impairment
E0 ConsensusPEM not requiredModerate confidenceReview-NarrativeEditor reviewed

Neuropsychology of chronic fatigue syndrome: a critical review.

Tiersky, L A, Johnson, S K, Lange, G et al.·Journal of clinical and experimental neuropsychology·1997

This review examined research on thinking and memory problems in ME/CFS patients. The clearest finding was that people with ME/CFS struggle with processing information quickly and efficiently, similar to when your brain feels sluggish. However, overall intelligence and complex thinking skills remain normal. Emotional factors like anxiety or depression can make cognitive problems feel worse, though it's unclear if they directly affect actual thinking performance.

Cognitive Impairment
E0 ConsensusPEM not requiredPreliminaryReview-NarrativeEditor reviewed

Neurocognitive functioning in chronic fatigue syndrome.

DiPino, R K, Kane, R L·Neuropsychology review·1996

This review examined research on thinking and memory problems reported by people with ME/CFS. While patients consistently describe difficulties concentrating and remembering things, scientific tests of these abilities have shown mixed and unclear results. The authors suggest that researchers need to improve how they design studies and what tests they use to better understand these cognitive challenges.

Cognitive Impairment
E0 ConsensusPEM not requiredPreliminaryReview-NarrativeEditor reviewed

Cognitive and mood-state changes in patients with chronic fatigue syndrome.

Grafman, J, Johnson, R, Scheffers, M·Reviews of infectious diseases·1991

This review examined whether ME/CFS causes problems with memory, thinking, and mood. The researchers found that while some people with acute mono or EBV infection may have thinking difficulties, they couldn't confirm this happens in ME/CFS patients using objective tests. However, they did notice that people with ME/CFS often have depression or anxiety either before or alongside their illness.

Cognitive Impairment
E0 ConsensusPEM not requiredPreliminaryReview-NarrativeEditor reviewed

Chronic fatigue syndrome and depression: cause, effect, or covariate.

Abbey, S E, Garfinkel, P E·Reviews of infectious diseases·1991

Many people with ME/CFS experience depression, but it's unclear why. This review examines four possible explanations: depression might be the main illness with fatigue as a symptom, depression might develop because of having ME/CFS, both conditions might occur together separately, or depression might be incorrectly diagnosed. The authors discuss how depression can affect medical tests used to study ME/CFS, which is important to understand when interpreting research results.

Cognitive Impairment
E0 ConsensusPEM not requiredPreliminarySystematic-ReviewEditor reviewed

Functional neurological disorder in people with long COVID: A systematic review.

Teodoro, Tiago, Chen, Jiaying, Gelauff, Jeannette et al.·European journal of neurology·2023

Researchers reviewed 102 studies about long COVID to see whether some of the neurological symptoms (such as brain fog, headaches, and dizziness) might be functional neurological disorder (FND)—a condition where the nervous system doesn't work properly without obvious physical damage. While these symptoms are common in long COVID, the studies didn't carefully look for the specific patterns that would help diagnose FND, so it remains unclear whether FND plays a role in long COVID.

Cognitive Impairment
E0 ConsensusPEM unclearModerate confidenceSystematic-ReviewEditor reviewed

Post-viral fatigue in COVID-19: A review of symptom assessment methods, mental, cognitive, and physical impairment.

Campos, Maria Cristine, Nery, Tatyana, Starke, Ana Carolina et al.·Neuroscience and biobehavioral reviews·2022

This review looked at how doctors and researchers measure fatigue in people who have long-term tiredness after COVID-19. The study found that fatigue after COVID-19 is common and can affect thinking, mood, and physical abilities. The researchers identified different tools—questionnaires and performance tests—that can help measure how tired someone feels and how much their tiredness limits their daily activities.

Cognitive Impairment
E0 ConsensusPEM not requiredPreliminaryReview-NarrativeEditor reviewed

Epidemiology, pathophysiology, and classification of the neurological symptoms of post-COVID-19 syndrome.

Carod-Artal, F J, García-Moncó, J C·Neurology perspectives·2021

This review examines long-term symptoms people experience after COVID-19 infection, particularly neurological (brain and nerve-related) symptoms like brain fog, memory problems, headaches, and sleep issues. The authors found that post-COVID-19 syndrome is complex and variable—affecting different people in different ways—and likely involves multiple causes including immune system changes, nerve dysfunction, and possibly persistent viral effects. Because the definition and criteria for post-COVID-19 syndrome remain unclear, reported rates of occurrence vary dramatically, ranging from 2% to 85% depending on the study.

Cognitive Impairment
E0 ConsensusPEM requiredModerate confidenceEditorialEditor reviewed

Myalgic encephalomyelitis/chronic fatigue syndrome and fibromyalgia - overlap, differences, and emerging insights.

Murovska, Modra, Krumina, Angelika, Araja, Diana et al.·Journal of translational medicine·2026

ME/CFS and fibromyalgia are two different but often overlapping illnesses that cause severe fatigue, pain, and other debilitating symptoms. While they share many similarities, ME/CFS has a distinctive feature called post-exertional malaise—where activity makes symptoms dramatically worse for hours or days—while fibromyalgia does not. This review shows that the two conditions have different immune system patterns and may require different treatment approaches.

Severe MEImmune SystemCognitive ImpairmentPost-Exertional Malaise
E0 ConsensusPEM requiredModerate confidenceReview-NarrativeEditor reviewed

Differential Characteristics and Comparison Between Long-COVID Syndrome and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

Ivanovska, Mariya, Homadi, Maysam Salim, Angelova, Gergana et al.·Biomedicines·2025

This review compared Long-COVID (illness after COVID-19) and ME/CFS (chronic fatigue syndrome), which share similar symptoms like extreme tiredness, difficulty thinking clearly, and problems with the nervous system. While both conditions likely involve immune system problems, viral persistence, and blood vessel issues, they appear to have some differences in how they develop. Currently, there is no cure for either condition, though lifestyle management and rehabilitation help some people.

Immune SystemCognitive ImpairmentPost-Exertional Malaise
E0 ConsensusPEM unclearPreliminaryReview-NarrativeEditor reviewed

Herpesvirus Infection of Endothelial Cells as a Systemic Pathological Axis in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Nunes, Jean M, Kell, Douglas B, Pretorius, Etheresia·Viruses·2024

This review examines the theory that a common virus family (herpesviruses) may infect the blood vessel lining in ME/CFS patients, potentially causing the disease's widespread symptoms. When these viruses damage blood vessels, they may disrupt blood flow, increase clotting problems, and affect brain function—all hallmarks of ME/CFS. The researchers suggest this endothelial (blood vessel) damage could explain why ME/CFS is chronic and affects multiple body systems.

Cognitive Impairment
E0 ConsensusPEM not requiredModerate confidenceReview-NarrativeEditor reviewed

Cognitive symptoms after COVID-19.

Altuna, M, Sánchez-Saudinós, Mª B, Lleó, A·Neurology perspectives·2021

COVID-19 can cause cognitive problems—such as difficulty thinking, concentrating, or remembering—that sometimes last for months after infection. These cognitive symptoms can happen even in people with mild COVID cases, which is unusual compared to other viral illnesses. This review found that cognitive problems after COVID share similarities with symptoms seen in ME/CFS and can significantly affect daily life and quality of life.

Cognitive Impairment
E0 ConsensusPEM not requiredModerate confidenceSystematic-ReviewEditor reviewed

Identification of mental health and quality of life outcomes in primary care databases in the UK: a systematic review.

Carreira, Helena, Williams, Rachael, Strongman, Helen et al.·BMJ open·2019

Researchers reviewed 120 studies that used UK patient medical records to track mental health and quality of life problems like depression, anxiety, fatigue, and cognitive issues. They found that different studies used different definitions and coding systems to identify these conditions, making it hard to compare results across studies. The authors recommend that researchers agree on standard definitions and validated code lists so findings are more consistent and reliable.

Pain and SensitizationSleepCognitive Impairment
E0 ConsensusPEM not requiredModerate confidenceReview-NarrativeEditor reviewed

Psychological impact of fibromyalgia: current perspectives.

Galvez-Sánchez, Carmen M, Duschek, Stefan, Reyes Del Paso, Gustavo A·Psychology research and behavior management·2019

Fibromyalgia is a chronic pain condition that often comes with fatigue, sleep problems, and difficulty concentrating. This review found that people with fibromyalgia frequently experience depression, anxiety, and other mental health challenges, and these psychological symptoms can make the physical illness worse. The study suggests that combining talk therapy or other psychological support with medication may help patients feel better and improve their quality of life.

Cognitive Impairment
E0 ConsensusPEM not requiredModerate confidenceSystematic-ReviewEditor reviewed

A unifying theory for cognitive abnormalities in functional neurological disorders, fibromyalgia and chronic fatigue syndrome: systematic review.

Teodoro, Tiago, Edwards, Mark J, Isaacs, Jeremy D·Journal of neurology, neurosurgery, and psychiatry·2018

Many people with ME/CFS report cognitive problems like brain fog, forgetfulness, and difficulty concentrating. This review of 95 studies found that while patients consistently describe these symptoms, standard memory and thinking tests often show normal or only mild problems. The authors suggest that pain, fatigue, and the body's excessive self-monitoring may force the brain to work harder on everyday tasks, making thinking feel more exhausting even when test results look relatively normal.

Cognitive Impairment
E0 ConsensusPEM unclearModerate confidenceReview-NarrativeEditor reviewed

Dysfunctional syndromes and fibromyalgia: a 2012 critical digest.

Sarzi-Puttini, Piercarlo, Atzeni, Fabiola, Di Franco, Manuela et al.·Clinical and experimental rheumatology·2012

This review looked at several long-lasting conditions that cause widespread pain, tiredness, sleep problems, and difficulty concentrating—conditions that don't always show up clearly on standard medical tests. The researchers examined fibromyalgia, ME/CFS, and irritable bowel syndrome to understand how they're connected and what causes symptoms to keep happening. They found that these conditions share similar patterns in how the nervous system processes pain and fatigue.

Pain and SensitizationCognitive Impairment
E0 ConsensusPEM not requiredModerate confidenceEditorialEditor reviewed

Central nervous system abnormalities in fibromyalgia and chronic fatigue syndrome: new concepts in treatment.

Gur, Ali, Oktayoglu, Pelin·Current pharmaceutical design·2008

This review examines how ME/CFS and fibromyalgia may both involve problems in the nervous system—specifically in how the brain processes pain, manages stress hormones, and controls automatic body functions. The authors discuss why current treatments are limited and explore new medication approaches that target brain chemicals involved in pain and fatigue.

SleepAutonomic Nervous SystemCognitive Impairment
E0 ConsensusPEM unclearPreliminaryReview-NarrativeEditor reviewed

War syndromes and their evaluation: from the U.S. Civil War to the Persian Gulf War.

Hyams, K C, Wignall, F S, Roswell, R·Annals of internal medicine·1996

Researchers reviewed historical records of illnesses that appeared in soldiers after wars, dating back to the U.S. Civil War through the Persian Gulf War. They found that across different wars and time periods, veterans reported similar symptoms like exhaustion, breathing problems, headaches, and difficulty concentrating. However, the researchers concluded that these symptoms don't appear to be one single disease, and that lack of proper comparison groups and research methods made it hard to determine what actually caused these illnesses.

Cognitive Impairment
E0 ConsensusPEM not requiredModerate confidenceMeta-AnalysisEditor reviewed

Post-Lyme borreliosis syndrome: a meta-analysis of reported symptoms.

Cairns, Victoria, Godwin, Jon·International journal of epidemiology·2005

This study looked at patients who had Lyme disease and found that many experienced long-lasting fatigue, muscle and joint pain, and thinking difficulties even after antibiotic treatment. Researchers combined results from five previous studies comparing Lyme disease patients to healthy controls and found these symptoms were significantly more common in the Lyme disease group. The symptom pattern was notably different from other conditions like fibromyalgia or depression.

Pain and SensitizationCognitive Impairment
E0 ConsensusPEM not requiredPreliminarySystematic-ReviewEditor reviewed

Review: How has cognitive behaviour therapy been adapted for adolescents with comorbid depression and chronic illness? A scoping review.

Morey, Alice, Loades, Maria E·Child and adolescent mental health·2021

This review looked at how therapy called cognitive behaviour therapy (CBT) has been modified to help teenagers with both depression and long-term illnesses like diabetes, chronic fatigue syndrome, and inflammatory bowel disease. The researchers found that CBT is often adapted by helping young people think differently about their illness, do activities they enjoy while managing their condition, and involving their family. However, there is still limited research showing how well these adapted treatments actually work for this group.

Cognitive Impairment
E0 ConsensusPEM unclearPreliminarySystematic-ReviewEditor reviewed

A systematic review of the association between fatigue and cognition in chronic noncommunicable diseases.

Menzies, Victoria, Kelly, Debra L, Yang, Gee S et al.·Chronic illness·2021

This review looked at 10 studies examining whether fatigue and cognitive problems (like brain fog or memory issues) are connected in people with chronic diseases, including ME/CFS. The researchers found that in a few studies, higher fatigue was linked with worse cognitive function, but overall there isn't enough research yet to be certain about this relationship. More studies are needed to understand how fatigue and thinking problems relate to each other.

Cognitive Impairment
E0 ConsensusPEM not requiredPreliminarySystematic-ReviewEditor reviewed

A Review Study on the Beneficial Effects of Baduanjin.

Zou, Liye, Pan, Zhujun, Yeung, Albert et al.·Journal of alternative and complementary medicine (New York, N.Y.)·2018

This review looked at 22 studies about Baduanjin, a gentle Chinese exercise that combines movement with mental focus. The studies suggest that Baduanjin may help improve thinking abilities, mood, sleep, and physical symptoms in people with various conditions, including those with chronic fatigue-like illness. However, the authors note that better-quality, longer-lasting studies are needed before we can be confident about these benefits.

Cognitive Impairment
E0 ConsensusPEM not requiredHigher confidenceMeta-AnalysisEditor reviewed

Behavior problems in children and adolescents with chronic physical illness: a meta-analysis.

Pinquart, Martin, Shen, Yuhui·Journal of pediatric psychology·2011

This large review of 569 studies found that children and teenagers with chronic physical illnesses—including ME/CFS—experience higher rates of emotional and behavioral problems compared to healthy peers. Children with ME/CFS showed particularly high levels of emotional problems like anxiety and depression. The review emphasizes that doctors should routinely screen young patients with chronic illnesses for psychological distress and refer them to mental health services when needed.

Cognitive Impairment
E0 ConsensusPEM unclearPreliminaryReview-NarrativeEditor reviewed

Approved and investigational uses of modafinil : an evidence-based review.

Kumar, Raminder·Drugs·2008

This review looked at studies testing modafinil, a medication that promotes wakefulness, in different conditions including sleep disorders and fatigue-related illnesses. The authors found that modafinil works well for approved conditions like narcolepsy and sleep apnea, but studies testing it for chronic fatigue syndrome were very small and gave unclear results. The medication can cause side effects like insomnia, headaches, and appetite loss, and may interact with other drugs.

SleepCognitive Impairment
E0 ConsensusPEM not requiredPreliminaryEditorialEditor reviewed

Medically unexplained symptoms and neuropsychological assessment.

Binder, Laurence M, Campbell, Keith A·Journal of clinical and experimental neuropsychology·2004

This review examines several long-term illnesses—including ME/CFS—where patients experience real symptoms but standard medical tests don't show an obvious cause. The authors found that some patients do have measurable thinking and memory problems, but these may result from a combination of stress, past trauma, and how the body responds to illness rather than from traditional brain disease alone.

Cognitive Impairment
E0 ConsensusPEM not requiredModerate confidenceSystematic-ReviewEditor reviewed

Psychological treatment of patients with chronic toxic encephalopathy: lessons from studies of chronic fatigue and whiplash.

van Hout, Moniek S E, Wekking, Ellie M, Berg, Ina J et al.·Psychotherapy and psychosomatics·2003

This review looked at studies on psychological treatments for chronic toxic encephalopathy (a condition from long-term solvent exposure) and compared them with research on chronic fatigue syndrome and whiplash injuries. The reviewers found that cognitive-behavioral therapy (CBT)—a type of talk therapy that helps change unhelpful thinking patterns—and gradually increasing activity levels showed promise in helping people with fatigue and thinking problems. They suggest these same approaches might help people with toxic encephalopathy, though more research is needed.

Cognitive Impairment
E1 ReplicatedPEM unclearModerate confidenceRCTEditor reviewed

Solriamfetol improves daily fatigue symptoms in adults with myalgic encephalomyelitis/chronic fatigue syndrome after 8 weeks of treatment.

Young, Joel L, Powell, Richard N, Powell, Anna et al.·Journal of psychopharmacology (Oxford, England)·2025

Researchers tested whether a medication called solriamfetol could help reduce fatigue in people with ME/CFS. In this 8-week study, some patients received the medication (starting at 75mg and potentially increasing to 150mg) while others received a placebo. By week 8, patients taking solriamfetol reported significantly less severe fatigue compared to those on placebo, and they also showed improvements in thinking and memory abilities. The medication was generally well tolerated, though some people experienced sleep problems and headaches.

Cognitive Impairment
E1 ReplicatedPEM unclearModerate confidenceRCTEditor reviewed

Relationships between fatigue, cognitive function, and upright activity in a randomized trial of oxaloacetate for myalgic encephalomyelitis/chronic fatigue syndrome.

Vernon, Suzanne D, Rond, Candace, Sun, Yifei et al.·Frontiers in neurology·2025

This study tested whether a compound called oxaloacetate (OAA) could help people with ME/CFS feel less fatigued and think more clearly. Over 90 days, people taking OAA showed better cognitive improvement and slightly more ability to stay upright compared to those taking a placebo. The results suggest that fatigue and thinking problems are closely linked in ME/CFS, and treating one may help improve the other.

Cognitive Impairment
E1 ReplicatedPEM requiredModerate confidenceRCTEditor reviewed

Assessing fatigue in myalgic encephalomyelitis/chronic fatigue syndrome patients before and after treatment with bright light therapy: A prospective randomized controlled crossover study.

Ludwig, Birgit, Hauer, Lea, Böck, Marion et al.·Sleep medicine·2025

Researchers tested whether bright light therapy—using special light boxes at home for two weeks—could help reduce fatigue in ME/CFS patients. While fatigue scores did improve immediately after the light therapy, these improvements did not remain significant when compared fairly to a waitlist control group. The study did find that bright light therapy may have helped patients concentrate better and react faster to tasks.

Autonomic Nervous SystemCognitive Impairment
E1 ReplicatedPEM unclearPreliminaryRCTEditor reviewed

Yeast Beta-Glucan Supplementation with Multivitamins Attenuates Cognitive Impairments in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial.

Lacasa, Marcos, Alegre-Martin, Jose, Sentañes, Ramon Sanmartin et al.·Nutrients·2023

This study tested whether a supplement made from yeast beta-glucan combined with vitamin D, B6, and zinc could help people with ME/CFS feel less mentally tired and think more clearly. Over 36 weeks, 65 ME/CFS patients took either the supplement or a placebo pill, and researchers measured changes in cognitive fatigue using a standard questionnaire. The group taking the beta-glucan supplement showed meaningful improvement in mental fatigue compared to the placebo group.

Cognitive Impairment
E1 ReplicatedPEM requiredModerate confidenceObservationalEditor reviewed

Cerebral blood flow is reduced in ME/CFS during head-up tilt testing even in the absence of hypotension or tachycardia

C. M. C. van Campen, F. C. Visser, P. C. Rowe·Journal of Internal Medicine·2020·n=429

In the largest study of its kind, 429 ME/CFS patients underwent head-up tilt testing with simultaneous cerebral blood flow monitoring. Nearly all ME/CFS patients showed significantly reduced cerebral blood flow when upright, even when blood pressure and heart rate were normal. The reduction correlated with symptom severity.

Autonomic Nervous SystemCognitive Impairment
E1 ReplicatedPEM not requiredPreliminaryRCTEditor reviewed

Use of lisdexamfetamine dimesylate in treatment of executive functioning deficits and chronic fatigue syndrome: a double blind, placebo-controlled study.

Young, Joel L·Psychiatry research·2013

This study tested whether a medication called lisdexamfetamine (LDX), which affects brain chemicals related to focus and attention, could help people with ME/CFS who struggle with executive functioning—skills like planning, organizing, and decision-making. Twenty-six participants took either the medication or a placebo for 6 weeks, and those on LDX showed significantly better improvements in executive functioning, fatigue, and pain compared to placebo.

Cognitive Impairment
E1 ReplicatedPEM not requiredModerate confidenceRCTEditor reviewed

Does neuropsychological test performance predict outcome of cognitive behavior therapy for Chronic Fatigue Syndrome and what is the role of underperformance?

Goedendorp, Martine M, van der Werf, Sieberen P, Bleijenberg, Gijs et al.·Journal of psychosomatic research·2013

This study looked at whether cognitive impairments (problems with thinking and memory) measured by tests could predict how well patients would improve with cognitive behavior therapy (CBT) for ME/CFS. Researchers also examined whether some patients might be doing poorly on tests due to not trying their best, rather than actual cognitive problems. The study found that while some patients did perform worse on these tests, this didn't predict whether CBT would help reduce fatigue or improve daily functioning—though patients who weren't trying their best were more likely to drop out of treatment.

Cognitive Impairment
E1 ReplicatedPEM not requiredModerate confidenceRCTEditor reviewed

The effect of cognitive behaviour therapy for chronic fatigue syndrome on self-reported cognitive impairments and neuropsychological test performance.

Knoop, Hans, Prins, Judith B, Stulemeijer, Maja et al.·Journal of neurology, neurosurgery, and psychiatry·2007

People with ME/CFS often report problems with concentration and memory. This study tested whether cognitive behavioural therapy (CBT)—a type of talk therapy—could help improve these cognitive problems. The researchers found that CBT did reduce how much patients *felt* their thinking was impaired, but it did not actually improve their performance on memory and attention tests.

Cognitive Impairment
E1 ReplicatedPEM not requiredModerate confidenceRCTEditor reviewed

Does methylphenidate reduce the symptoms of chronic fatigue syndrome?

Blockmans, Daniel, Persoons, Philippe, Van Houdenhove, Boudewijn et al.·The American journal of medicine·2006

This study tested whether methylphenidate (a stimulant medication) could help reduce fatigue and improve concentration in ME/CFS patients. Sixty patients took either methylphenidate or placebo for 4 weeks each in alternating order. The medication did reduce fatigue and concentration problems compared to placebo, but only about 17–22% of patients showed clinically meaningful improvement.

Cognitive Impairment
E1 ReplicatedPEM not requiredPreliminaryRCTEditor reviewed

Chronic treatment with modafinil may not be beneficial in patients with chronic fatigue syndrome.

Randall, Delia C, Cafferty, Fay H, Shneerson, John M et al.·Journal of psychopharmacology (Oxford, England)·2005

This study tested whether modafinil, a medication that promotes wakefulness, could help 14 ME/CFS patients think more clearly and feel less tired. Patients took either modafinil (at two different doses) or placebo in a blinded, controlled trial. The results were mixed: some thinking tasks improved slightly at the lower dose, but higher doses actually made some tasks harder, and fatigue ratings didn't improve at all.

Cognitive Impairment
E1 ReplicatedPEM not requiredPreliminaryRCTEditor reviewed

Exploratory open label, randomized study of acetyl- and propionylcarnitine in chronic fatigue syndrome.

Vermeulen, Ruud C W, Scholte, Hans R·Psychosomatic medicine·2004

This study tested whether two types of carnitine supplements—acetylcarnitine, propionylcarnitine, or both together—could help reduce fatigue in ME/CFS patients. Over 24 weeks, about 59–63% of patients taking either supplement alone reported significant improvement in fatigue and concentration, though acetylcarnitine worked better for mental fatigue while propionylcarnitine worked better for general fatigue. Unfortunately, most patients experienced worsening fatigue within 2 weeks after stopping treatment.

Cognitive Impairment
E1 ReplicatedPEM not requiredModerate confidenceRCTEditor reviewed

Examining the influence of biological and psychological factors on cognitive performance in chronic fatigue syndrome: a randomized, double-blind, placebo-controlled, crossover study.

Smith, Simon, Sullivan, Karen·International journal of behavioral medicine·2003

This study tested whether cognitive problems (like difficulty concentrating) in people with ME/CFS are caused by actual chemical exposure or by what people believe they are being exposed to. Thirty-six patients were given either a placebo or a chemical trigger while not knowing which one they received, and their thinking ability was tested before and after. The results showed that cognitive performance got worse when patients thought they had been exposed to a chemical, regardless of what they actually received.

Cognitive Impairment
E1 ReplicatedPEM not requiredPreliminaryMechanisticEditor reviewed

Neuropsychological performance and noradrenaline function in chronic fatigue syndrome under conditions of high arousal.

Morriss, Richard K, Robson, Michael J, Deakin, J F William·Psychopharmacology·2002

This study tested whether people with ME/CFS have unusually sensitive brain receptors that respond to a hormone-like drug called clonidine. Researchers gave 10 ME/CFS patients and 10 healthy controls either clonidine or a placebo while they performed stressful thinking tasks, and measured their hormones, blood pressure, and thinking speed. ME/CFS patients showed slightly stronger hormone responses to clonidine and were faster at starting a planning task, suggesting their brains may react more strongly to stress-related chemical signals.

Cognitive Impairment
E1 ReplicatedPEM not requiredPreliminaryRCTEditor reviewed

An assessment of cognitive function and mood in chronic fatigue syndrome.

Marshall, P S, Watson, D, Steinberg, P et al.·Biological psychiatry·1996

This study tested whether ME/CFS affects how quickly people think and process information, how fast they can move, and their mood. Researchers gave patients cognitive tests and mood surveys before and after treatment with either an active medication or placebo. They found that people with ME/CFS were slower at thinking tasks and had more difficulty experiencing positive emotions, but their ability to focus and pay attention was not noticeably impaired.

Cognitive Impairment
E1 ReplicatedPEM not requiredPreliminaryRCTEditor reviewed

A prospective randomized, double-blind placebo-controlled study to evaluate the effectiveness of neuroprotective therapy using functional brain MRI in patients with post-covid chronic fatigue syndrome.

Tanashyan, M, Morozova, S, Raskurazhev, A et al.·Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie·2023

Researchers tested whether a drug called CCSA (a compound containing succinate acid) could help people with post-COVID fatigue and brain fog. They used advanced brain imaging scans to measure changes in brain activity before and after treatment. The CCSA group showed greater improvement in fatigue symptoms and thinking skills compared to the placebo group.

Cognitive Impairment
E1 ReplicatedPEM not requiredModerate confidenceObservationalEditor reviewed

Kinesiophobia and maladaptive coping strategies prevent improvements in pain catastrophizing following pain neuroscience education in fibromyalgia/chronic fatigue syndrome: An explorative study.

Malfliet, Anneleen, Van Oosterwijck, Jessica, Meeus, Mira et al.·Physiotherapy theory and practice·2017

This study looked at why some people with ME/CFS and fibromyalgia benefit more from a type of pain education (called pain neuroscience education) than others. The researchers found that patients who were very afraid of movement or who tended to worry a lot about their pain showed less improvement in their catastrophic thinking about pain after receiving this education. This suggests that for some patients, education alone may not be enough—they might need additional support to address their fears and worries.

Pain and SensitizationCognitive Impairment
E1 ReplicatedPEM not requiredWeak / uncertainRCTEditor reviewed

Homeopathy for mental fatigue: lessons from a randomized, triple blind, placebo-controlled cross-over clinical trial.

Dean, Michael Emmans, Karsandas, Raj, Bland, J Martin et al.·BMC complementary and alternative medicine·2012

This study tested whether a homeopathic remedy called Kali phos 6x could help people with mental fatigue focus better. Eighty-six university students and staff took either the remedy or a placebo, then did a concentration test. The remedy did not work better than placebo, and the researchers found that the test was too easy for most participants to show whether the remedy made a real difference.

Cognitive Impairment
E2 ModeratePEM unclearModerate confidenceLongitudinalEditor reviewed

Validation of the Wood Mental Fatigue Inventory in adolescents with myalgic encephalomyelitis/chronic fatigue syndrome.

Welch, David C, Edwards, Charles C, Broussard, Camille A et al.·Brain, behavior, & immunity - health·2026

This study tested whether a questionnaire called the Wood Mental Fatigue Inventory (WMFI) works well for measuring brain fog and cognitive problems in teenagers with ME/CFS. Researchers compared it to another commonly used teen fatigue scale and found that both questionnaires measured mental fatigue similarly and could track changes over time as teenagers received treatment.

Cognitive Impairment
E2 ModeratePEM requiredModerate confidenceCross-SectionalEditor reviewed

The association of fatigue and pain with cognitive test performance in patients with myalgic encephalomyelitis/chronic fatigue syndrome.

Oosterman, Joukje M, van der Schaaf, Marieke, de Kleijn, Willemien P E et al.·Journal of psychosomatic research·2025

This study looked at how fatigue and pain affect thinking and memory problems in people with ME/CFS. Researchers tested 1,375 patients on tasks like reaction time and attention, and found that both fatigue severity and pain severity were linked to worse cognitive performance. The effects were stronger in older patients, suggesting that age may play a role in how much fatigue and pain impact thinking abilities.

Pain and SensitizationCognitive Impairment
E2 ModeratePEM unclearModerate confidenceCross-SectionalEditor reviewed

Comparative Study Between Cognitive Phenotypes of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Multiple Sclerosis.

Aoun Sebaiti, Mehdi, Oubaya, Nadia, Gounden, Yannick et al.·Diagnostics (Basel, Switzerland)·2025

This study compared thinking and memory problems in ME/CFS patients with those in multiple sclerosis (MS) patients, since both conditions can cause similar cognitive issues, fatigue, and pain. Researchers tested 40 people with ME/CFS and 40 with MS using standard memory and attention tests. They found that ME/CFS patients have a specific pattern of cognitive difficulties, particularly problems with consolidating (storing) new information in memory, which is distinct from MS.

Cognitive Impairment
E2 ModeratePEM unclearModerate confidenceObservationalEditor reviewed

Absence of BOLD adaptation in chronic fatigue syndrome revealed by task functional MRI.

Schönberg, Laura, Mohamed, Abdalla Z, Yu, Qiang et al.·Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism·2025

This study looked at how the brain responds when people with ME/CFS do mental tasks, using brain imaging to measure blood flow. Researchers found that while healthy people's brains become more efficient with repeated effort (showing less activation over time), people with ME/CFS showed the opposite pattern—their brains actually increased activity with each repetition. This suggests that ME/CFS may involve a fundamental difference in how the brain adapts to mental work, potentially explaining why cognitive tasks feel so exhausting.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Cognitive functioning in patients with chronic fatigue syndrome: Slowed information processing or a deficit in attentional selectivity?

Banovic, Ingrid, Šaban, Iva, Ayad, Adel et al.·Neuropsychology·2025

This study tested whether people with ME/CFS have trouble focusing their attention or simply process information more slowly. Researchers gave 83 ME/CFS patients and 83 healthy people a simple attention test (the Stroop task) where they had to name colors while ignoring conflicting words. The results showed that ME/CFS patients were slower overall, but their difficulty wasn't due to problems with attention—it was purely because their brains processed information more slowly.

Cognitive Impairment
E2 ModeratePEM unclearModerate confidenceCross-SectionalEditor reviewed

Plasma Neurofilament Light Chain: A Potential Biomarker for Neurological Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Azcue, Naiara, Tijero-Merino, Beatriz, Acera, Marian et al.·Biomedicines·2024

Researchers measured a protein called neurofilament light chain (NfL) in the blood of ME/CFS patients and healthy people. They found that ME/CFS patients had higher levels of this protein, which suggests nerve damage in the brain and nervous system. The patients with higher NfL levels also had more problems with memory, thinking clearly, and with their autonomic nervous system (the part that controls heart rate and other automatic body functions).

Autonomic Nervous SystemCognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Cognitive reserve as a protective factor against cognitive impairment in chronic fatigue syndrome.

Surendran, Gopika, Jose, Tony P·Applied neuropsychology. Adult·2024

This study examined whether people's life experiences and education—called 'cognitive reserve'—help protect them from the thinking and memory problems common in ME/CFS. Researchers tested 91 people with ME/CFS and found that those with more cognitive reserve had fewer cognitive problems. The severity of someone's ME/CFS was the main factor affecting both cognitive reserve and cognitive problems, rather than age or gender.

Cognitive Impairment
E2 ModeratePEM unclearPreliminaryMechanisticEditor reviewed

Phenylephrine alters phase synchronization between cerebral blood velocity and blood pressure in ME/CFS with orthostatic intolerance.

Medow, Marvin S, Stewart, Julian M·American journal of physiology. Regulatory, integrative and comparative physiology·2024

People with ME/CFS often experience brain fog and cognitive problems when standing up, possibly because their brain isn't getting enough blood flow and oxygen. This study tested whether a medication called phenylephrine could help restore brain blood flow and improve thinking during standing. The researchers found that phenylephrine was the only treatment tested that significantly improved both cognitive performance and the brain's ability to maintain stable blood flow during head-up tilting.

Autonomic Nervous SystemCognitive Impairment
E2 ModeratePEM requiredModerate confidenceCross-SectionalEditor reviewed

Connectivity Between Salience and Default Mode Networks and Subcortical Nodes Distinguishes Between Two Classes of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Su, Jiasheng, Thapaliya, Kiran, Eaton-Fitch, Natalie et al.·Brain connectivity·2023

This study used brain imaging (fMRI) to examine how different brain networks communicate in people with ME/CFS compared to healthy controls. Researchers found that people with ME/CFS have different patterns of brain connectivity, particularly in networks involved in attention and the brain's rest-state activity. Importantly, the study discovered that two different diagnostic criteria for ME/CFS (ICC and Fukuda) appear to identify distinct brain differences, suggesting they may represent different disease types.

Cognitive Impairment
E2 ModeratePEM unclearPreliminaryCross-SectionalEditor reviewed

Subcortical and default mode network connectivity is impaired in myalgic encephalomyelitis/chronic fatigue syndrome.

Inderyas, Maira, Thapaliya, Kiran, Marshall-Gradisnik, Sonya et al.·Frontiers in neuroscience·2023

This study used advanced brain imaging to compare how different brain regions communicate in people with ME/CFS versus healthy people. Researchers found that certain connections between the brainstem (the lower part of the brain) and cerebellum (involved in balance and coordination) are weakened in ME/CFS patients. These brain communication problems may help explain why people with ME/CFS experience fatigue, memory problems, and other symptoms.

Cognitive Impairment
E2 ModeratePEM unclearModerate confidenceCross-SectionalEditor reviewed

The Conners Continuous Performance Test CPT3™: Is it a reliable marker to predict neurocognitive dysfunction in Myalgic encephalomyelitis/chronic fatigue syndrome?

Fernández-Quirós, Judith, Lacasa-Cazcarra, Marcos, Alegre-Martín, Jose et al.·Frontiers in psychology·2023

This study tested whether a computer-based attention test called CPT3™ can reliably detect thinking and concentration problems in ME/CFS patients. Researchers compared 158 ME/CFS patients with 67 healthy people and found that ME/CFS patients performed significantly worse on measures of attention, focus, and reaction speed. The test successfully identified differences between the two groups, suggesting it could be a useful tool for doctors to help diagnose or monitor ME/CFS.

Cognitive Impairment
E2 ModeratePEM requiredPreliminaryCross-SectionalEditor reviewed

Alteration of Cortical Volume and Thickness in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Thapaliya, Kiran, Marshall-Gradisnik, Sonya, Staines, Donald et al.·Frontiers in neuroscience·2022

Researchers used brain imaging to compare the brains of people with ME/CFS to healthy people. They found that people with ME/CFS had some areas of the brain that were thinner and other areas that were larger, particularly in regions involved in thinking and emotion. These brain differences were also connected to how severe symptoms like fatigue, sleep problems, and cognitive difficulties were in each person.

Cognitive Impairment
E2 ModeratePEM requiredModerate confidenceCross-SectionalEditor reviewed

Volumetric differences in hippocampal subfields and associations with clinical measures in myalgic encephalomyelitis/chronic fatigue syndrome.

Thapaliya, Kiran, Staines, Donald, Marshall-Gradisnik, Sonya et al.·Journal of neuroscience research·2022

Researchers used brain imaging to examine a part of the brain called the hippocampus, which is important for memory and thinking. They found that people with ME/CFS who met stricter diagnostic criteria had some structural differences in specific regions of their hippocampus compared to healthy people, and these differences were connected to how severe their fatigue and pain were. This finding supports the idea that ME/CFS involves real physical changes in the brain that may explain memory and cognitive problems patients experience.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Cognitive Task Performance and Subjective Cognitive Symptoms in Individuals With Chronic Fatigue Syndrome or Fibromyalgia: A Cross-Sectional Analysis of the Lifelines Cohort Study.

Joustra, Monica L, Hartman, Catharina A, Bakker, Stephan J L et al.·Psychosomatic medicine·2022

This study looked at thinking and memory problems in people with ME/CFS and fibromyalgia by testing nearly 80,000 people. Researchers found that people with ME/CFS reported significantly more trouble concentrating and had slightly slower performance on thinking tasks compared to healthy people and those with other diseases like multiple sclerosis. These cognitive complaints remained even when researchers accounted for depression, anxiety, and physical symptom severity.

Cognitive Impairment
E2 ModeratePEM requiredPreliminaryCross-SectionalEditor reviewed

The role of low-grade inflammation in ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) - associations with symptoms.

Jonsjö, Martin A, Olsson, Gunnar L, Wicksell, Rikard K et al.·Psychoneuroendocrinology·2020

This study looked at whether low-level inflammation in the blood is connected to ME/CFS symptoms like exhaustion after activity, brain fog, muscle pain, and flu-like illness. Researchers tested 53 ME/CFS patients for various inflammatory markers and found that several of these markers were associated with cognitive problems and pain, though they were surprisingly less connected to post-exertional fatigue. Interestingly, the connection between inflammation and symptoms was different for men and women in some cases.

BiomarkersImmune SystemCognitive ImpairmentPost-Exertional Malaise
E2 ModeratePEM unclearModerate confidenceCross-SectionalEditor reviewed

Health-related quality of life in patients with myalgic encephalomyelitis/chronic fatigue syndrome: an Australian cross-sectional study.

Eaton-Fitch, N, Johnston, S C, Zalewski, P et al.·Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation·2020

This Australian study of 480 people with ME/CFS found that the condition severely impacts quality of life across all major areas—physical functioning, emotional well-being, pain, and energy levels. People with ME/CFS scored much lower on quality of life measures compared to the general population, with the lowest scores for physical activities and fatigue. The study identified specific symptoms like cognitive difficulties, sleep problems, and cardiovascular issues that are most strongly linked to reduced quality of life.

Pain and SensitizationSleepCognitive Impairment
E2 ModeratePEM not requiredPreliminaryObservationalEditor reviewed

Feedback on underperformance in patients with Chronic Fatigue Syndrome: The impact on subsequent neuropsychological test performance.

Roor, Jeroen J, Knoop, Hans, Dandachi-FitzGerald, Brechje et al.·Applied neuropsychology. Adult·2020

This study looked at whether telling ME/CFS patients about their poor performance on memory tests could help them do better on brain function tests afterward. Researchers gave one group of patients feedback about underperformance while another group got no feedback. The group that received feedback showed meaningful improvement in processing speed (how quickly the brain handles information), suggesting that simple feedback might help doctors get a more accurate picture of a patient's actual cognitive abilities.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Do adolescents with chronic fatigue syndrome (CFS/ME) and co-morbid anxiety and/or depressive symptoms think differently to those who do not have co-morbid psychopathology?

Loades, Maria E, Stallard, Paul, Morris, Richard et al.·Journal of affective disorders·2020

This study looked at how adolescents with ME/CFS think about their symptoms, comparing those who also have anxiety or depression with those who don't. Teenagers with both ME/CFS and anxiety/depression were more likely to have negative thoughts in general and worry more about their fatigue causing damage or embarrassment. The thinking patterns of both groups together explained about 43% of why some teens developed anxiety or depression alongside their ME/CFS.

Cognitive Impairment
E2 ModeratePEM unclearModerate confidenceObservationalEditor reviewed

Resting-state functional connectivity, cognition, and fatigue in response to cognitive exertion: a novel study in adolescents with chronic fatigue syndrome.

Josev, Elisha K, Malpas, Charles B, Seal, Marc L et al.·Brain imaging and behavior·2020

Researchers compared how the brains of teenagers with ME/CFS and healthy teenagers responded to a mentally demanding task using brain imaging. Both groups showed similar changes in brain activity and felt more tired after the mental effort. However, teenagers with ME/CFS started out more fatigued, performed worse on thinking tasks overall, and may have less energy available to draw from when their brain works hard.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Associations of occupational stress, workplace violence, and organizational support on chronic fatigue syndrome among nurses.

Li, Mengyao, Shu, Qianyi, Huang, Hao et al.·Journal of advanced nursing·2020

This study examined whether workplace stress, violence, and lack of organizational support increase the risk of ME/CFS in nurses. Researchers surveyed 1,080 Chinese nurses and found that those experiencing high levels of overcommitment, workplace violence, and little support from their employers were significantly more likely to have ME/CFS. The findings suggest that improving workplace safety, support, and reducing internal stress could help prevent ME/CFS in this high-risk group.

SleepCognitive Impairment
E2 ModeratePEM unclearPreliminaryLongitudinalEditor reviewed

The Impact of a Structured Exercise Programme upon Cognitive Function in Chronic Fatigue Syndrome Patients.

Zalewski, Paweł, Kujawski, Sławomir, Tudorowska, Malwina et al.·Brain sciences·2019

This study tested whether a 16-week structured exercise program could help improve 'brain fog' and thinking problems that many people with ME/CFS experience. Of 53 patients who started the program, 34 completed it. Tests showed that those who finished the program had modest improvements in attention and processing speed, particularly in how quickly and accurately they could respond to visual tasks.

Cognitive Impairment
E2 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

Cognitive and behavioral coping in people with Chronic fatigue syndrome: An exploratory study searching for intervention targets for depressive symptoms.

Kraaij, Vivian, Bik, Janneke, Garnefski, Nadia·Journal of health psychology·2019

This study looked at how 30 people with ME/CFS cope with depression by using different thinking and behavior strategies. The researchers found that the way people think about and reframe their problems has a bigger impact on depression than what they do. Focusing on positive aspects, looking at problems in a different light, and avoiding catastrophizing (imagining the worst) seemed to help the most.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Neuropsychological dysfunction in chronic fatigue syndrome and the relation between objective and subjective findings.

Rasouli, Omid, Gotaas, Merethe Eide, Stensdotter, Ann-Katrin et al.·Neuropsychology·2019

This study tested whether people with ME/CFS who report having trouble thinking and remembering actually show problems on objective cognitive tests. Researchers gave 236 patients questionnaires about memory difficulties and gave them various thinking tests. They found that patients' own reports of cognitive problems didn't strongly match their actual test results, but those with higher fatigue, pain, and depression tended to report more thinking difficulties. The actual cognitive problems found on testing were mainly in speed of thinking and attention.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCase-ControlEditor reviewed

Cognitive and behavioural responses to symptoms in adolescents with chronic fatigue syndrome: A case-control study nested within a cohort.

Loades, Maria Elizabeth, Rimes, Katharine, Lievesley, Kate et al.·Clinical child psychology and psychiatry·2019

This study looked at how adolescents with ME/CFS think about and respond to their symptoms, compared to teenagers with asthma. Researchers found that young people with ME/CFS tend to have unhelpful thought patterns—like believing symptoms cause permanent damage—and unhelpful behaviors like pushing through activity or avoiding it completely. These unhelpful patterns were linked to more fatigue and disability over a 3-month follow-up period.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Impairments in cognitive performance in chronic fatigue syndrome are common, not related to co-morbid depression but do associate with autonomic dysfunction.

Robinson, Lucy J, Gallagher, Peter, Watson, Stuart et al.·PloS one·2019

This study found that people with ME/CFS often experience slowing in thinking speed and processing information, particularly in tasks requiring quick reactions. Importantly, these cognitive difficulties are not caused by depression—even patients without depression showed the same thinking problems. The researchers discovered that problems with heart rate regulation (how the body's autonomic nervous system works) were linked to these cognitive difficulties.

Autonomic Nervous SystemCognitive Impairment
E2 ModeratePEM unclearModerate confidenceCross-SectionalEditor reviewed

Visual Aspects of Reading Performance in Myalgic Encephalomyelitis (ME).

Wilson, Rachel L, Paterson, Kevin B, McGowan, Victoria et al.·Frontiers in psychology·2018

This study tested reading and vision abilities in 27 people with ME/CFS and compared them to healthy controls. Researchers found that people with ME/CFS read more slowly and had greater difficulty reading when text was crowded together, even though their basic vision was similar to controls. These findings suggest that vision-related reading problems in ME/CFS are real and measurable, not just imagined.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Cross-Cultural Study of Information Processing Biases in Chronic Fatigue Syndrome: Comparison of Dutch and UK Chronic Fatigue Patients.

Hughes, Alicia M, Hirsch, Colette R, Nikolaus, Stephanie et al.·International journal of behavioral medicine·2018

This study looked at how people with ME/CFS pay attention to and interpret information related to illness and symptoms. Researchers in the Netherlands and UK tested whether people with ME/CFS tend to notice illness-related words more quickly and interpret unclear situations in ways related to their symptoms. They found that people with ME/CFS did show these patterns, and importantly, these patterns were similar in both countries, suggesting this is a consistent feature of the condition rather than a cultural difference.

Cognitive Impairment
E2 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

Static and dynamic functional connectivity in patients with chronic fatigue syndrome: use of arterial spin labelling fMRI.

Boissoneault, Jeff, Letzen, Janelle, Lai, Song et al.·Clinical physiology and functional imaging·2018

Researchers used a brain imaging technique to compare how the brains of people with ME/CFS and healthy people process information during a tiring mental task. They found that people with ME/CFS had different patterns of communication between brain regions, and these patterns were linked to how fatigued they felt. This suggests that the fatigue experienced in ME/CFS may be related to how different parts of the brain work together.

Cognitive Impairment
E2 ModeratePEM not requiredPreliminaryCase-ControlEditor reviewed

Cognitive remediation training improves performance in patients with chronic fatigue syndrome.

McBride, Richard L, Horsfield, Sarah, Sandler, Carolina X et al.·Psychiatry research·2017

This study tested whether computer-based brain training exercises could help ME/CFS patients with concentration and memory problems. Thirty-six patients received standard cognitive-behavioral therapy plus exercise therapy, and thirty-six received the same treatment plus online cognitive training. The group that added brain training showed greater improvements in both their self-reported memory and concentration, and also performed better on objective memory and thinking tests.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCase-ControlEditor reviewed

Are current chronic fatigue syndrome criteria diagnosing different disease phenotypes?

Maclachlan, Laura, Watson, Stuart, Gallagher, Peter et al.·PloS one·2017

This study looked at whether different diagnostic criteria for ME/CFS are actually identifying the same disease or different versions of it. Researchers tested 49 ME/CFS patients and 10 healthy controls using questionnaires and objective tests of heart function and thinking ability. They found that patients reported more autonomic and cognitive symptoms than controls, but objective heart tests didn't show clear differences—though different patient subgroups did show different levels of impairment on cognitive testing.

Autonomic Nervous SystemDiagnosticsCognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

An attention and interpretation bias for illness-specific information in chronic fatigue syndrome.

Hughes, A M, Chalder, T, Hirsch, C R et al.·Psychological medicine·2017

This study looked at whether people with ME/CFS notice illness-related information more than healthy people, and whether they tend to interpret unclear situations in a health-focused way. Researchers found that people with ME/CFS do pay more attention to fatigue-related words and are more likely to interpret ambiguous situations negatively related to their health compared to healthy controls. These thought patterns were connected to beliefs about fear and avoidance, suggesting they may help keep ME/CFS symptoms going.

Cognitive Impairment
E2 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

Altered right anterior insular connectivity and loss of associated functions in adolescent chronic fatigue syndrome.

Wortinger, Laura Anne, Glenne Øie, Merete, Endestad, Tor et al.·PloS one·2017

This study looked at how the brains of adolescents with ME/CFS work differently compared to healthy teenagers. Researchers used brain imaging to examine a region called the anterior insula, which helps coordinate motivation and responses to pain. They found that this brain region had weaker connections to areas involved in thinking and decision-making in ME/CFS patients, which may help explain why patients struggle with concentration, pain sensitivity, and physical activity.

Cognitive Impairment
E2 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

Abnormal resting state functional connectivity in patients with chronic fatigue syndrome: an arterial spin-labeling fMRI study.

Boissoneault, Jeff, Letzen, Janelle, Lai, Song et al.·Magnetic resonance imaging·2016

This study used a special brain imaging technique to look at how different parts of the brain communicate with each other in ME/CFS patients compared to healthy people. Researchers found that people with ME/CFS have unusual patterns of brain communication, particularly in areas related to memory, thinking, and movement. Importantly, the strength of connections in memory-related brain regions was linked to how severe patients' fatigue symptoms were.

Cognitive Impairment
E2 ModeratePEM not requiredPreliminaryObservationalEditor reviewed

Long-term methylphenidate intake in chronic fatigue syndrome.

Blockmans, Daniel, Persoons, Philippe·Acta clinica Belgica·2016

This study looked at whether a medication called methylphenidate (also known as Ritalin) could help ME/CFS patients with concentration problems and fatigue over the long term. Researchers sent surveys to patients who had been prescribed this medication and found that about one-third of those still taking it reported significant improvement in both fatigue and concentration difficulties, and were able to work more hours.

Cognitive Impairment
E2 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

Low putamen activity associated with poor reward sensitivity in childhood chronic fatigue syndrome.

Mizuno, Kei, Kawatani, Junko, Tajima, Kanako et al.·NeuroImage. Clinical·2016

This study looked at how the brains of children with ME/CFS respond to rewards compared to healthy children. Using brain imaging, researchers found that a brain region called the putamen (involved in motivation) showed less activity in children with ME/CFS, especially when facing smaller rewards. Lower activity in this area was linked to worse fatigue and less enjoyment from learning.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

The impact of chronic fatigue syndrome on cognitive functioning in adolescents.

Nijhof, Linde N, Nijhof, Sanne L, Bleijenberg, Gijs et al.·European journal of pediatrics·2016

This study looked at how ME/CFS affects thinking and concentration in teenagers. Researchers compared 59 teenagers with ME/CFS to 40 healthy teenagers and found that those with ME/CFS had lower scores on intelligence tests than their school grades would predict. When comparing teenagers' current test scores to their performance before they got sick, the ME/CFS group showed a significant decline, while healthy teens did not.

Cognitive Impairment
E2 ModeratePEM requiredModerate confidenceCross-SectionalEditor reviewed

Chronic Fatigue Syndrome versus Systemic Exertion Intolerance Disease.

Jason, Leonard A, Sunnquist, Madison, Brown, Abigail et al.·Fatigue : biomedicine, health & behavior·2015

Researchers compared different ways of diagnosing ME/CFS by testing 796 patients using a new diagnostic system called SEID (Systemic Exertion Intolerance Disease). They found that the new SEID criteria identified about 88% of patients, which is similar to an older diagnostic system but captures a larger group than some other definitions. The study suggests that different diagnostic criteria can identify different sizes and severity levels of patient populations.

Cognitive ImpairmentPost-Exertional Malaise
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Study findings challenge the content validity of the Canadian Consensus Criteria for adolescent chronic fatigue syndrome.

Asprusten, Tarjei Tørre, Fagermoen, Even, Sulheim, Dag et al.·Acta paediatrica (Oslo, Norway : 1992)·2015

Researchers tested whether the Canadian Consensus Criteria—a set of guidelines used to diagnose ME/CFS in teenagers—actually identify meaningful differences between patients. They compared 120 adolescents with ME/CFS, grouping them by whether they met these criteria or not. The study found that the two groups were nearly identical in most disease markers and how they recovered over time, suggesting the criteria may not be capturing important real-world differences between patients.

Cognitive Impairment
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A Cross Cultural Comparison of Disability and Symptomatology Associated with CFS.

Zdunek, Maria, Jason, Leonard A, Evans, Meredyth et al.·International journal of psychology and behavioral sciences·2015

This study compared ME/CFS symptoms and disability between patients in the United States and the United Kingdom to see if the illness looks different depending on where people live. Researchers found that UK patients reported more mental health problems, pain, memory/concentration issues, and immune symptoms, while US patients more often experienced sudden illness onset and attributed their illness to physical causes. The study suggests that ME/CFS may present somewhat differently across these two countries.

Pain and SensitizationSleepCognitive Impairment
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The effect of fatigue and fibromyalgia on sexual dysfunction in women with chronic fatigue syndrome.

Blazquez, Alicia, Ruiz, Eva, Aliste, Luisa et al.·Journal of sex & marital therapy·2015

This study examined sexual problems in 615 women with ME/CFS and found that sexual dysfunction was more common in those with worse fatigue, more cognitive and nervous system symptoms, and co-occurring conditions like fibromyalgia or Sjögren's syndrome. The researchers used a validated questionnaire to measure sexual satisfaction and identified patterns linking symptom severity to sexual health problems. This suggests that ME/CFS symptoms directly impact intimate relationships and sexual function.

Cognitive Impairment
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Computerized training improves verbal working memory in patients with myalgic encephalomyelitis/chronic fatigue syndrome: A pilot study.

Maroti, Daniel, Westerberg, Annika Fryxell, Saury, Jean-Michel et al.·Journal of rehabilitation medicine·2015

Many people with ME/CFS struggle with memory and thinking problems. This small study tested whether spending 30-45 minutes a day for 5 weeks doing computerized memory exercises on a computer could help. Nine out of eleven patients who completed the training showed real improvements in working memory and attention, while a control group of patients who didn't do the training showed no improvement.

Cognitive Impairment
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Attention network test: assessment of cognitive function in chronic fatigue syndrome.

Togo, Fumiharu, Lange, Gudrun, Natelson, Benjamin H et al.·Journal of neuropsychology·2015

This study tested whether a computer-based attention test called the Attention Network Task (ANT) could measure thinking and processing speed problems in ME/CFS patients. Researchers compared 41 ME/CFS patients (some with depression, some without) to 29 healthy controls and found that ME/CFS patients took longer to respond to tasks, especially when the tasks were complex, even though they made the same number of mistakes as controls. This suggests that slowed thinking speed, rather than errors, may be the main cognitive problem in ME/CFS.

Cognitive Impairment
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The association between daytime napping and cognitive functioning in chronic fatigue syndrome.

Gotts, Zoe M, Ellis, Jason G, Deary, Vincent et al.·PloS one·2015

This study looked at how sleep patterns, especially daytime napping, affect fatigue, sleepiness, and thinking ability in people with ME/CFS. Researchers asked 118 patients to keep a sleep diary for two weeks and complete daily assessments of their symptoms. They found that afternoon napping was linked to worse cognitive problems and increased daytime sleepiness, suggesting that when and how much patients nap may influence how well they can think and function.

SleepCognitive Impairment
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Neuropsychological impairment in female patients with chronic fatigue syndrome: a preliminary study.

Santamarina-Perez, Pilar, Eiroa-Orosa, Francisco Jose, Rodriguez-Urrutia, Amanda et al.·Applied neuropsychology. Adult·2014

This study looked at thinking and memory problems in 68 women with ME/CFS using standardized cognitive tests. Researchers found that about half of patients had difficulties with attention and motor skills, while 40% struggled with processing information quickly and with executive functions like planning. The severity of fatigue and emotional factors were linked to some of these cognitive difficulties.

Cognitive Impairment
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Psychosocial factors involved in memory and cognitive failures in people with myalgic encephalomyelitis/chronic fatigue syndrome.

Attree, Elizabeth A, Arroll, Megan A, Dancey, Christine P et al.·Psychology research and behavior management·2014

This study looked at how memory and concentration problems in ME/CFS are connected to emotional and physical factors. Researchers asked 87 people with ME/CFS about their fatigue, mood, anxiety, and support systems, then measured their memory and cognitive problems. They found that fatigue, depression, and a person's sense of personal capability were linked to memory difficulties and thinking problems.

Cognitive Impairment
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Attention processes in chronic fatigue syndrome: attentional bias for health-related threat and the role of attentional control.

Hou, Ruihua, Moss-Morris, Rona, Risdale, Anna et al.·Behaviour research and therapy·2014

This study looked at whether people with ME/CFS pay more attention to health-related words and images, and whether difficulty controlling attention might be connected to this pattern. Researchers found that people with ME/CFS do tend to focus more on health-threat words, and many also have trouble with executive attention (the mental control needed to stay focused). Importantly, people with ME/CFS who had weaker attention control showed the strongest focus on health threats.

Cognitive Impairment
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Cognitive functioning in people with chronic fatigue syndrome: a comparison between subjective and objective measures.

Cockshell, Susan J, Mathias, Jane L·Neuropsychology·2014

This study looked at whether people with ME/CFS who report memory and concentration problems actually perform worse on cognitive tests. Fifty people with ME/CFS and 50 healthy controls completed questionnaires about their cognitive difficulties and took standardized memory and attention tests. Surprisingly, while people with ME/CFS reported significantly more cognitive problems in daily life, both groups performed similarly on the objective tests, and reported problems didn't match test results in either group.

Cognitive Impairment
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Association between cognitive performance, physical fitness, and physical activity level in women with chronic fatigue syndrome.

Ickmans, Kelly, Clarys, Peter, Nijs, Jo et al.·Journal of rehabilitation research and development·2013

This study looked at whether people with ME/CFS who have better thinking skills (like memory and reaction time) also tend to be more physically fit or active. Researchers tested 31 women with ME/CFS and 13 healthy women on thinking tasks and physical fitness measures. They found that physical fitness—especially heart and muscle function—was linked to thinking speed, but daily activity levels were not.

Cognitive Impairment
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Patterns of abnormal visual attention in myalgic encephalomyelitis.

Hutchinson, Claire V, Badham, Stephen P·Optometry and vision science : official publication of the American Academy of Optometry·2013

This study tested whether people with ME/CFS have difficulty with visual attention—the ability to focus on and track things they see. Researchers compared 29 patients with ME/CFS to 29 healthy people using eye-tracking tests. The results showed that ME/CFS patients did struggle more with certain types of visual attention tasks, particularly when they had to focus on specific things or search for objects, supporting what many patients report experiencing.

Cognitive Impairment
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Cognitions, behaviours and co-morbid psychiatric diagnoses in patients with chronic fatigue syndrome.

Cella, M, White, P D, Sharpe, M et al.·Psychological medicine·2013

This study looked at how often certain thought patterns and behaviors occur in ME/CFS patients, and whether these patterns differ when patients also have depression or anxiety. Researchers surveyed 640 ME/CFS patients and found that more than half had ME/CFS alone, while the rest also had depression and/or anxiety. Different thinking patterns appeared in patients with different mental health combinations—for example, patients with anxiety were more likely to focus heavily on their symptoms, while those with depression were more likely to avoid activities.

Cognitive Impairment
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Cognitive performance is of clinical importance, but is unrelated to pain severity in women with chronic fatigue syndrome.

Ickmans, Kelly, Meeus, Mira, Kos, Daphne et al.·Clinical rheumatology·2013

This study looked at whether cognitive problems (thinking, memory, attention) in women with ME/CFS are related to pain severity. Researchers gave cognitive tests and questionnaires to 29 women with ME/CFS and 17 healthy women. They found that cognitive problems were NOT linked to pain levels, but were connected to fatigue and mental health, suggesting that cognitive difficulties in ME/CFS may work differently than in other chronic pain conditions.

Pain and SensitizationCognitive Impairment
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Relationship between autonomic cardiovascular control, case definition, clinical symptoms, and functional disability in adolescent chronic fatigue syndrome: an exploratory study.

Wyller, Vegard B, Helland, Ingrid B·BioPsychoSocial medicine·2013

This study looked at how the nervous system controls heart rate in teenagers with ME/CFS and how this relates to their symptoms and disability. Researchers tested 38 teenagers using a tilt test (lying flat then tilting upright) while measuring heart rate changes, and asked them about their symptoms. They found that disability in ME/CFS comes from multiple symptoms—not just fatigue—and that problems with heart rate control are linked to certain symptoms like brain fog and sensitivity to stimulation.

Autonomic Nervous SystemCognitive Impairment
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Cognitive deficits in chronic fatigue syndrome and their relationship to psychological status, symptomatology, and everyday functioning.

Cockshell, Susan J, Mathias, Jane L·Neuropsychology·2013

Researchers compared thinking and memory skills between 50 people with ME/CFS and 50 healthy people. They found that people with ME/CFS were slower at processing information (like reaction time), but performed normally on other thinking tasks like memory and attention. Interestingly, this slowness was not explained by depression, anxiety, fatigue, or sleep problems.

Cognitive Impairment
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Reduced cardiac vagal modulation impacts on cognitive performance in chronic fatigue syndrome.

Beaumont, Alison, Burton, Alexander R, Lemon, Jim et al.·PloS one·2012

This study examined whether problems with the heart's automatic nervous system (which controls heart rate) are connected to cognitive difficulties in ME/CFS patients. Researchers measured heart rate variability—the natural variation in time between heartbeats—while 30 ME/CFS patients and 40 healthy controls performed thinking tasks. ME/CFS patients showed slower thinking speeds and unusual heart rate patterns, and their reduced heart rate variability was linked to their cognitive slowness.

Autonomic Nervous SystemCognitive Impairment
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Attention-deficit hyperactivity disorder in chronic fatigue syndrome patients.

Sáez-Francàs, Naia, Alegre, José, Calvo, Natalia et al.·Psychiatry research·2012

This study looked at whether people with ME/CFS also have ADHD (attention-deficit hyperactivity disorder), a condition that affects focus and attention. Researchers found that about 30% of ME/CFS patients had ADHD as children, and about 21% still had it as adults. People with ME/CFS who also had ADHD experienced worse depression and anxiety, more severe fatigue, and higher suicide risk than those without ADHD.

Cognitive Impairment
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Test effort in persons with Chronic Fatigue Syndrome when assessed using the Validity Indicator Profile.

Cockshell, Susan J, Mathias, Jane L·Journal of clinical and experimental neuropsychology·2012

This study tested whether people with ME/CFS perform poorly on thinking tests because they aren't trying hard enough, or because of the illness itself. Researchers gave 54 people with ME/CFS and 54 healthy people a special test designed to measure effort and intention during testing. The results showed that most people in both groups were trying their best, and very few showed signs of not putting in effort—suggesting that low effort is not the reason people with ME/CFS struggle with cognitive tasks.

Cognitive Impairment
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Regional grey and white matter volumetric changes in myalgic encephalomyelitis (chronic fatigue syndrome): a voxel-based morphometry 3 T MRI study.

Puri, B K, Jakeman, P M, Agour, M et al.·The British journal of radiology·2012

Researchers used a specialized MRI brain scan to compare 26 ME/CFS patients with 26 healthy volunteers. They found that patients had smaller volumes of brain tissue in specific areas related to vision, memory, and movement coordination. These structural changes in the brain may help explain why ME/CFS patients often experience memory problems and other cognitive difficulties.

Cognitive Impairment
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[The role of depression in cognitive impairment in patients with chronic fatigue syndrome].

Santamarina-Pérez, Pilar, Freniche, Verónica, Eiroa-Orosa, Francisco Jose et al.·Medicina clinica·2011

This study tested whether depression explains the thinking and memory problems that people with ME/CFS experience. Researchers gave 57 women with ME/CFS a variety of cognitive tests measuring attention, memory, and processing speed, then compared results between those with and without depression. The findings showed that cognitive problems were present in ME/CFS patients regardless of whether they had depression, suggesting that the brain fog and thinking difficulties are part of ME/CFS itself, not caused by depression.

Cognitive Impairment
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What to do about attention and memory problems in children with CFS/ME: a neuropsychological approach.

Tucker, Peter, Haig-Ferguson, Andrew, Eaton, Nicola et al.·Clinical child psychology and psychiatry·2011

Children with ME/CFS often experience problems with concentration, attention, and memory—difficulties that go beyond normal tiredness. This study tested children's attention and memory abilities and found they scored lower than expected on tasks involving sustained focus, switching between tasks, and remembering new information. The researchers suggest practical strategies that could help children manage these cognitive challenges in daily life.

Cognitive Impairment
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Length of illness does not predict cognitive dysfunction in chronic fatigue syndrome.

Santamarina-Perez, Pilar, Eiroa-Orosa, Francisco Jose, Freniche, Verónica et al.·Applied neuropsychology·2011

This study examined whether cognitive problems (like memory and concentration difficulties) in ME/CFS get worse the longer someone has the illness. Researchers tested 56 women with ME/CFS and divided them into groups based on how long they'd been sick. They found that cognitive problems were similar across all groups, regardless of illness duration. This suggests that cognitive difficulties in ME/CFS don't progressively worsen over time.

Cognitive Impairment
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Psychomotor function and response inhibition in chronic fatigue syndrome.

Van Den Eede, Filip, Moorkens, Greta, Hulstijn, Wouter et al.·Psychiatry research·2011

This study tested whether people with ME/CFS have slower hand movements and difficulty controlling automatic responses compared to healthy people. Patients and controls completed computer tasks that involved copying patterns while the researchers measured how fast they reacted and moved. The results showed that ME/CFS patients were noticeably slower at both reacting and moving, but they were equally able to control their automatic responses when the patterns were harder to draw.

Cognitive Impairment
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Cognitive dysfunction and mental fatigue in childhood chronic fatigue syndrome--a 6-month follow-up study.

Kawatani, Junko, Mizuno, Kei, Shiraishi, Seishi et al.·Brain & development·2011

This study looked at thinking and attention problems in children with ME/CFS using a specialized test that measures how quickly and accurately the brain can process information. Children with ME/CFS performed worse on attention tasks compared to healthy children, especially when they had to switch between different tasks. After 6 months of combined treatment with therapy and medication, children showed improvements in both their thinking ability and fatigue levels.

Cognitive Impairment
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Cognitive deficits in patients with chronic fatigue syndrome compared to those with major depressive disorder and healthy controls.

Constant, E L, Adam, S, Gillain, B et al.·Clinical neurology and neurosurgery·2011

This study tested memory and attention in people with ME/CFS, comparing them to people with depression and healthy volunteers. People with ME/CFS showed real, measurable problems with attention and memory, but these problems were NOT simply caused by depression or by getting tired during testing. Importantly, the cognitive difficulties in ME/CFS appeared to be their own distinct issue, separate from their mood symptoms.

Cognitive Impairment
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Mood volatility with rumination but neither attentional nor interpretation biases in chronic fatigue syndrome.

Martin, Maryanne, Alexeeva, Iana·British journal of health psychology·2010

This study looked at whether people with ME/CFS have a tendency to automatically focus their attention on illness-related information, and whether they interpret ambiguous words in an illness-focused way. The researchers found that people with ME/CFS did not show these automatic biases. However, they did find that people with ME/CFS experienced greater mood swings when they spent time thinking repetitively about their condition (rumination) compared to when they were distracted.

Cognitive Impairment
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Orthostatic symptoms predict functional capacity in chronic fatigue syndrome: implications for management.

Costigan, A, Elliott, C, McDonald, C et al.·QJM : monthly journal of the Association of Physicians·2010

This study found that ME/CFS patients have much greater difficulty with daily activities compared to healthy people. Among ME/CFS patients, those who experience dizziness or lightheadedness when standing up (orthostatic symptoms) had the most trouble with physical functioning. The researchers suggest that treating these standing-related symptoms might help patients do more in their daily lives.

Autonomic Nervous SystemCognitive Impairment
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Coenzyme Q10 deficiency in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is related to fatigue, autonomic and neurocognitive symptoms and is another risk factor explaining the early mortality in ME/CFS due to cardiovascular disorder.

Maes, Michael, Mihaylova, Ivanka, Kubera, Marta et al.·Neuro endocrinology letters·2009

This study found that people with ME/CFS have significantly lower levels of Coenzyme Q10 (CoQ10), a substance that helps cells produce energy, compared to healthy people. Nearly 45% of ME/CFS patients had CoQ10 levels below what was found in any of the healthy control group. Low CoQ10 was connected to worse fatigue, problems with heart and blood pressure regulation, and difficulty with thinking and memory.

Autonomic Nervous SystemCognitive Impairment
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An investigation into the cognitive deficits associated with chronic fatigue syndrome.

Thomas, Marie, Smith, Andrew·The open neurology journal·2009

This study tested whether people with ME/CFS have real problems with thinking and memory, not just imagine they do. The researchers gave a large group of properly diagnosed ME/CFS patients a thorough set of cognitive tests and found clear evidence of cognitive difficulties. Importantly, these problems were not caused by depression or anxiety, suggesting they are a direct part of the illness.

Cognitive Impairment
E2 ModeratePEM unclearPreliminaryCross-SectionalEditor reviewed

Illness intrusiveness in myalgic encephalomyelitis: an exploratory study.

Goudsmit, E M, Stouten, B, Howes, S·Journal of health psychology·2009

This study looked at how much ME disrupts different areas of patients' lives—work, social activities, hobbies, and relationships. Researchers asked 24 people with ME about their symptoms, how disabled they felt, and their mood. They found that ME significantly intrudes on daily life, and this intrusion was linked to fatigue, brain fog, disability, and depression. Patients who had ME plus other health conditions reported even more life disruption than those with ME alone.

Cognitive Impairment
E2 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

An assessment of prospective memory retrieval in women with chronic fatigue syndrome using a virtual-reality environment: an initial study.

Attree, Elizabeth A, Dancey, Christine P, Pope, Alison L·Cyberpsychology & behavior : the impact of the Internet, multimedia and virtual reality on behavior and society·2009

This study examined memory problems in women with ME/CFS using a computer-based virtual environment. Researchers tested two types of memory: remembering things after they happen (like recalling a list of words) and remembering to do something in the future (like remembering to take medication). Women with ME/CFS showed noticeable difficulties with both types of memory, particularly with recalling information, though some future-memory tasks showed only subtle differences.

Cognitive Impairment
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Neuropsychological functioning, illness perception, mood and quality of life in chronic fatigue syndrome, autoimmune thyroid disease and healthy participants.

Dickson, A, Toft, A, O'Carroll, R E·Psychological medicine·2009

This study compared thinking and memory skills, mood, and quality of life in people with ME/CFS, people with thyroid disease, and healthy people. People with ME/CFS showed more problems with memory, attention, and concentration, plus higher levels of anxiety and depression. Importantly, the attention problems stayed even after researchers accounted for mood issues, suggesting cognitive problems are a core feature of ME/CFS rather than just a result of feeling depressed or anxious.

Cognitive Impairment
E2 ModeratePEM unclearPreliminaryCross-SectionalEditor reviewed

Chronic fatigue syndrome in adolescents: do parental expectations of their child's intellectual ability match the child's ability?

Godfrey, Emma, Cleare, Anthony, Coddington, Alice et al.·Journal of psychosomatic research·2009

This study looked at whether parents of teenagers with ME/CFS have unrealistic expectations about their child's intellectual abilities compared to parents of healthy teenagers. Researchers tested the actual IQ of 28 teenagers with ME/CFS and 29 healthy teenagers, and also asked them and their parents what they thought their abilities were. They found that parents of teenagers with ME/CFS believed their children were more intelligent than they actually tested, more so than parents of healthy teenagers did.

Cognitive Impairment
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Attentional bias towards health-threat information in chronic fatigue syndrome.

Hou, Ruihua, Moss-Morris, Rona, Bradley, Brendan P et al.·Journal of psychosomatic research·2008

This study tested whether people with ME/CFS pay more attention to health-related threats compared to neutral information. Researchers used a simple computer task showing words and pictures related to health threats or neutral topics, and found that people with ME/CFS did indeed focus more on the health-threat information than healthy people did. This pattern of attention might help explain why some cognitive therapy approaches can be helpful for ME/CFS.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceLongitudinalEditor reviewed

Increase in prefrontal cortical volume following cognitive behavioural therapy in patients with chronic fatigue syndrome.

de Lange, Floris P, Koers, Anda, Kalkman, Joke S et al.·Brain : a journal of neurology·2008

This study found that ME/CFS patients have less brain tissue volume in certain areas compared to healthy people, but this loss can partially reverse with cognitive behavioural therapy (CBT). Patients who received CBT showed improvement in their symptoms, physical activity, and thinking speed, and their brain scans revealed increased grey matter volume in the prefrontal cortex (the front part of the brain involved in decision-making). This suggests that some of the brain changes seen in ME/CFS may not be permanent and could improve with effective treatment.

Cognitive Impairment
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Neuropsychological performance in persons with chronic fatigue syndrome: results from a population-based study.

Majer, Matthias, Welberg, Leonie A M, Capuron, Lucile et al.·Psychosomatic medicine·2008

This study compared thinking and motor skills in people with ME/CFS to healthy controls using computerized tests. People with ME/CFS showed slower reaction times and had more difficulty with memory tasks that involve holding and manipulating information in mind. These differences held up even after excluding people with psychiatric conditions or those taking medications that affect thinking.

Cognitive Impairment
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A twin study of cognitive function in chronic fatigue syndrome: the effects of sudden illness onset.

Claypoole, Keith H, Noonan, Carolyn, Mahurin, Roderick K et al.·Neuropsychology·2007

This study compared 22 pairs of identical twins where one had ME/CFS and the other was healthy. Researchers gave both twins thinking and memory tests to see if ME/CFS affects the brain. Twins with ME/CFS had slower processing speed, weaker verbal memory, slower motor responses, and more difficulty with complex thinking tasks, even though they had the same genetic background as their healthy twin.

Cognitive Impairment
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Probing the working memory system in chronic fatigue syndrome: a functional magnetic resonance imaging study using the n-back task.

Caseras, Xavier, Mataix-Cols, David, Giampietro, Vincent et al.·Psychosomatic medicine·2006

Researchers used brain imaging to study how people with ME/CFS perform memory tasks. Although patients and healthy people did equally well on the tasks, their brains used different patterns of activity—patients showed unusual activation in certain brain regions during easier tasks and reduced activity in key memory areas during harder tasks. This suggests that people with ME/CFS may need to work harder mentally to achieve the same results.

Cognitive Impairment
E2 ModeratePEM unclearModerate confidenceCross-SectionalEditor reviewed

Sub-typing CFS patients on the basis of 'minor' symptoms.

Janal, Malvin N, Ciccone, Donald S, Natelson, Benjamin H·Biological psychology·2006

This study looked at 161 women with ME/CFS to see if different symptom patterns might point to different types of the illness. Researchers found three possible subtypes: one involving muscle and joint pain, one resembling infectious illness, and one affecting the brain and thinking. People with the brain-related subtype had more trouble with memory and attention, while those with the muscle/joint subtype were more likely to also have fibromyalgia.

Cognitive Impairment
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Cognitive dysfunction relates to subjective report of mental fatigue in patients with chronic fatigue syndrome.

Capuron, Lucile, Welberg, Leonie, Heim, Christine et al.·Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology·2006

People with ME/CFS often report trouble thinking clearly, but researchers haven't always found proof of this on tests. This study found that cognitive problems are real, but mainly in patients who experience significant mental fatigue. When researchers gave cognitive tests to ME/CFS patients, those with high mental fatigue showed genuine difficulties with memory and attention, while those with low mental fatigue performed normally.

Cognitive Impairment
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Exercise and cognitive performance in chronic fatigue syndrome.

Cook, Dane B, Nagelkirk, Paul R, Peckerman, Arnold et al.·Medicine and science in sports and exercise·2005

This study tested whether a 25-minute light exercise session affected thinking and memory skills in people with ME/CFS. Researchers found that people with ME/CFS alone showed slower thinking speed and less consistent performance on cognitive tests compared to healthy people, but light exercise did not make their thinking worse. Interestingly, people with ME/CFS plus fibromyalgia did not show these cognitive problems.

Cognitive Impairment
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[Clinical characteristics of patients with chronic fatigue syndrome: analysis of 82 cases].

Li, Yong-Jie, Wang, De-Xin, Bai, Xiao-Li et al.·Zhonghua yi xue za zhi·2005

This study examined 82 Chinese patients with ME/CFS to understand what symptoms they experience and what might be causing their illness. Researchers found that most patients had memory and attention problems alongside fatigue, many showed signs of anxiety or depression, and some had low levels of a substance called L-carnitine (which helps produce energy) or evidence of a viral infection. When patients took L-carnitine supplements, their levels improved and symptoms got better.

Cognitive Impairment
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[Cognitive function and psychological characteristics of patients with chronic fatigue syndrome].

Li, Yong-jie, Gao, Xu-guang, Wang, De-Xin et al.·Zhonghua yi xue za zhi·2005

This study looked at how ME/CFS affects thinking and memory in 91 Chinese patients compared to 30 healthy people. Researchers found that 90% of ME/CFS patients had problems with memory and attention, and most also experienced depression, anxiety, and obsessive thoughts. The results show that ME/CFS causes real cognitive problems that are different from those seen in psychiatric illnesses alone.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceLongitudinalEditor reviewed

Illness and disability in Danish Chronic Fatigue Syndrome patients at diagnosis and 5-year follow-up.

Andersen, M M, Permin, H, Albrecht, F·Journal of psychosomatic research·2004

This study followed 33 people with ME/CFS for 5 years to see how their illness affected their daily lives. Researchers found that most people remained severely disabled, with very few experiencing meaningful recovery. While emotional well-being sometimes improved over time, problems like difficulty reading and allergies often got worse.

Cognitive Impairment
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Neuropsychological deficits in patients with chronic fatigue syndrome.

Busichio, Kim, Tiersky, Lana A, Deluca, John et al.·Journal of the International Neuropsychological Society : JINS·2004

This study tested how thinking and memory work in people with ME/CFS compared to healthy people. Researchers gave 141 ME/CFS patients and 76 healthy volunteers a series of brain function tests. They found that ME/CFS patients performed noticeably worse on tests measuring attention, processing speed, and motor skills, with some showing significant difficulties across multiple areas.

Cognitive Impairment
E2 ModeratePEM unclearModerate confidenceCross-SectionalEditor reviewed

Working memory deficits in chronic fatigue syndrome: differentiating between speed and accuracy of information processing.

Deluca, John, Christodoulou, Christopher, Diamond, Bruce J et al.·Journal of the International Neuropsychological Society : JINS·2004

This study tested how quickly people with ME/CFS can process information (like reading or hearing something fast) and how well they can hold information in their working memory (like remembering a phone number while writing it down). The researchers found that people with ME/CFS without mental health conditions had slower information processing speeds, but their memory ability was normal. Interestingly, people with ME/CFS who also had depression or anxiety showed similar results to healthy people.

Cognitive Impairment
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Cognitive processing in monozygotic twins discordant for chronic fatigue syndrome.

Mahurin, Roderick K, Claypoole, Keith H, Goldberg, Jack H et al.·Neuropsychology·2004

This study tested thinking and processing speed in identical twins where one had ME/CFS and one didn't, compared to healthy people without the condition. Researchers found that both twin groups—even the healthy ones—were slower at tasks requiring quick thinking compared to unrelated healthy controls, but both groups performed equally well on untimed thinking tasks. This suggests that slower processing speed may run in families rather than being caused by ME/CFS itself.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceLongitudinalEditor reviewed

Predictors of outcome in fatigued employees on sick leave: results from a randomised trial.

Huibers, Marcus J H, Bleijenberg, Gijs, van Amelsvoort, Ludovic G P M et al.·Journal of psychosomatic research·2004

This study followed 151 tired employees on sick leave for one year to see who recovered and who returned to work. The researchers found that about 43% of people stopped having persistent fatigue, and 62% went back to work. Interestingly, getting better from fatigue and returning to work were driven by different factors—people who recovered from fatigue tended to view their condition differently psychologically, while those who returned to work tended to be younger, male, and have fewer thinking/memory problems.

Cognitive Impairment
E2 ModeratePEM unclearPreliminaryObservationalEditor reviewed

[Biologically active food additives for correction of the chronic fatigue syndrome].

Dotsenko, V A, Mosiĭchuk, L V, Paramonov, A E·Voprosy pitaniia·2004

This study looked at whether a nutritional supplement made from beer yeast called 'Nagipol' might help people with ME/CFS. Researchers gave the supplement to patients and found improvements in fatigue, thinking ability, mood symptoms, and some blood markers. The authors suggest it could be useful as part of dietary treatment for ME/CFS, especially for patients who are overweight.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Functional status, neuropsychological functioning, and mood in chronic fatigue syndrome (CFS): relationship to psychiatric disorder.

Tiersky, Lana A, Matheis, Robert J, Deluca, John et al.·The Journal of nervous and mental disease·2003

This study looked at how depression and anxiety affect people with ME/CFS. Researchers compared four groups: people with ME/CFS alone, people with ME/CFS plus mental health symptoms that started after CFS, people with ME/CFS plus mental health symptoms that started before CFS, and healthy controls. The main finding was that while mental health problems don't make the physical fatigue and weakness worse, they do make people feel more emotionally distressed—especially if those mental health issues came before the CFS diagnosis.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Perception of cognitive performance in patients with chronic fatigue syndrome.

Metzger, Fredric A, Denney, Douglas R·Annals of behavioral medicine : a publication of the Society of Behavioral Medicine·2002

This study looked at how accurately people with ME/CFS judge their own mental performance. When patients with ME/CFS completed a challenging thinking task, they consistently thought they did worse than they actually did, even though their actual performance matched healthy people's performance. This gap between what they thought they could do and what they actually accomplished was linked to how mentally tired and fatigued the task made them feel.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Cognitive functioning in chronic fatigue syndrome and the role of depression, anxiety, and fatigue.

Short, Keryn, McCabe, Marita, Tooley, Greg·Journal of psychosomatic research·2002

This study tested whether people with ME/CFS have actual problems with memory and thinking skills, or whether the difficulty they experience is mainly related to depression, anxiety, or fatigue. Researchers compared 23 people with ME/CFS to 23 healthy people using both objective tests (like memory tasks) and subjective reports (how people felt their thinking was affected). The findings showed that on actual cognitive tests, people with ME/CFS performed just as well as healthy controls, though they reported feeling that their thinking was worse.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

The relations among body consciousness, somatic symptom report, and information processing speed in chronic fatigue syndrome.

van der Werf, Sieberen P, de Vree, Berna, van Der Meer, Jos W M et al.·Neuropsychiatry, neuropsychology, and behavioral neurology·2002

This study looked at whether paying too much attention to bodily sensations and reporting many physical symptoms might slow down how quickly people with ME/CFS can process information and react to tasks. Researchers measured how fast patients could respond to simple tests and found that people who were highly aware of their body sensations reported more symptoms and performed more slowly on reaction time tests. The study suggests that increased attention to the body may be partly responsible for the cognitive slowing that people with ME/CFS experience.

Cognitive Impairment
E2 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

[Relationship between chronic fatigue and subjective symptoms of fatigue with performance status (P.S.) and subjective fatigue scale for young adults (SFS-Y)].

Kobayashi, Hidetsugu, Demura, Shinichi·[Nihon koshu eisei zasshi] Japanese journal of public health·2002

This study looked at whether a new questionnaire (the SFS-Y) could help identify young people experiencing chronic fatigue by measuring different types of tiredness symptoms. Researchers gave the questionnaire to over 1,100 teenagers and found that the tool was quite good at spotting chronic fatigue, especially when it measured difficulty concentrating. The results suggest this questionnaire might be useful for screening young people who could develop ME/CFS-like conditions.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceMethods-PaperEditor reviewed

Validation of a telephone cognitive assessment test battery for use in chronic fatigue syndrome.

McCue, P, Scholey, A B, Herman, C et al.·Journal of telemedicine and telecare·2002

This study tested whether a telephone-based brain function test could accurately detect thinking problems in people with ME/CFS. Researchers compared two versions of the same test—one on a computer and one done by telephone—in 30 people with ME/CFS and 30 healthy people. Both versions showed that people with ME/CFS were significantly slower at thinking tasks involving attention, memory, and focus, confirming that cognitive problems are real and measurable in this illness.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Divided attention deficits in patients with chronic fatigue syndrome.

Ross, S, Fantie, B, Straus, S F et al.·Applied neuropsychology·2001

This study compared thinking and attention abilities in people with ME/CFS and healthy controls. Researchers found that ME/CFS patients had specific trouble with divided attention—the ability to focus on two things at once (like listening to someone while reading). However, they performed normally on other cognitive tests like memory and word-finding. This suggests that ME/CFS affects one particular type of thinking rather than overall intelligence.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Intraindividual variability in cognitive performance in persons with chronic fatigue syndrome.

Fuentes, K, Hunter, M A, Strauss, E et al.·The Clinical neuropsychologist·2001

This study tested how well 14 people with ME/CFS and 16 healthy people could perform thinking tasks over 10 weeks. While the ME/CFS group completed tasks more slowly, they were just as accurate. The key finding was that people with ME/CFS showed much more inconsistency in their performance from week to week—sometimes doing better, sometimes worse—even when doing the same type of task.

Cognitive Impairment
E2 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

Information processing in chronic fatigue syndrome: a preliminary investigation of suggestibility.

DiClementi, J D, Schmaling, K B, Jones, J F·Journal of psychosomatic research·2001

This study looked at how the brain processes information in people with ME/CFS compared to healthy people. Researchers found that people with ME/CFS reported more symptoms and were more easily influenced by suggestions, but they actually performed similarly to healthy people on memory and thinking tests. The findings suggest that how our brains automatically process information and respond to suggestions may affect how much people feel their thinking is impaired.

Cognitive Impairment
E2 ModeratePEM unclearModerate confidenceCase-ControlEditor reviewed

Neurobehavioral deficits associated with chronic fatigue syndrome in veterans with Gulf War unexplained illnesses.

Binder, L M, Storzbach, D, Campbell, K A et al.·Journal of the International Neuropsychological Society : JINS·2001

This study looked at whether Gulf War veterans with chronic fatigue syndrome (CFS) had thinking and memory problems. Researchers compared 32 veterans with CFS to 62 healthy veterans using thinking and memory tests. They found that veterans with CFS did show some cognitive difficulties, even when the researchers accounted for differences in how smart people were before they got sick.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Working memory deficits associated with chronic fatigue syndrome.

Dobbs, B M, Dobbs, A R, Kiss, I·Journal of the International Neuropsychological Society : JINS·2001

This study tested memory and thinking skills in 20 people with ME/CFS and compared them to 20 healthy people. The researchers found that people with ME/CFS performed worse on difficult memory tasks, particularly those requiring quick mental switching and staying focused despite distractions. However, their basic memory storage ability was normal.

Cognitive Impairment
E2 ModeratePEM unclearModerate confidenceCross-SectionalEditor reviewed

What is chronic fatigue syndrome? Heterogeneity within an international multicentre study.

Wilson, A, Hickie, I, Hadzi-Pavlovic, D et al.·The Australian and New Zealand journal of psychiatry·2001

This study looked at 744 people with chronic fatigue across eight countries to see if they formed different groups based on their symptoms. Researchers found two distinct subgroups: a larger group (68%) with less severe illness and fewer psychiatric issues, and a smaller group (32%) whose symptoms looked more like somatoform illness (where psychological factors strongly influence physical symptoms). Importantly, the proportion of people in each group varied dramatically between countries (6-48%), suggesting that how doctors diagnose and classify ME/CFS is not standardized worldwide.

DiagnosticsCognitive Impairment
E2 ModeratePEM not requiredModerate confidenceLongitudinalEditor reviewed

Longitudinal assessment of neuropsychological functioning, psychiatric status, functional disability and employment status in chronic fatigue syndrome.

Tiersky, L A, DeLuca, J, Hill, N et al.·Applied neuropsychology·2001

Researchers tracked 35 people with ME/CFS over about 3.5 years to see how they changed over time. They found that attention, mood, fatigue, and disability improved somewhat during this period. However, most people remained significantly disabled and unemployed at the end of the study, suggesting that while some aspects may get better, ME/CFS typically leaves people unable to work long-term.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Symptom patterns in long-duration chronic fatigue syndrome.

Friedberg, F, Dechene, L, McKenzie, M J et al.·Journal of psychosomatic research·2000

This study looked at how ME/CFS symptoms change over time by comparing people who had been ill for 10+ years with those ill for only a few years. Researchers found that people with longer illness duration reported more severe cognitive problems (like memory and concentration issues), while both groups had immune-related symptoms and flu-like symptoms. The study suggests that ME/CFS symptoms may shift and worsen in specific ways as the illness persists.

Cognitive Impairment
E2 ModeratePEM unclearModerate confidenceCross-SectionalEditor reviewed

Abnormal neuropsychological findings are not necessarily a sign of cerebral impairment: a matched comparison between chronic fatigue syndrome and multiple sclerosis.

van der Werf, S P, Prins, J B, Jongen, P J et al.·Neuropsychiatry, neuropsychology, and behavioral neurology·2000

This study compared how people with ME/CFS and people with multiple sclerosis (MS) performed on memory and thinking tests. The researchers found that people with ME/CFS were more likely to show signs of reduced effort on memory tests, but both groups had similar rates of poor performance on standard cognitive tests. This suggests that poor test results in ME/CFS patients might sometimes reflect how hard they're trying during the test, rather than actual brain damage.

Cognitive Impairment
E2 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

[The chronic fatigue and neurasthenia in the student population].

Mojarro Práxedes MD, Benjumea Pino P·Actas espanolas de psiquiatria·1999

This study looked at fatigue in 277 medical students to see how common chronic fatigue syndrome (CFS) and a related condition called neurasthenia actually are. The researchers found that while over one-third of students reported fatigue, very few met the strict criteria for CFS (less than 1%), and a small number met criteria for neurasthenia (about 3%). The study also found that students with fatigue were more likely to have depression symptoms, though it's unclear whether depression causes fatigue or results from it.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Acute fatigue in chronic fatigue syndrome patients.

Smith, A P, Borysiewicz, L, Pollock, J et al.·Psychological medicine·1999

This study tested whether people with ME/CFS get tired more quickly during mental tasks than healthy people. Researchers compared 67 ME/CFS patients with 126 healthy controls while they performed attention tests over a long session. ME/CFS patients performed worse than healthy people, and the gap widened as fatigue set in, suggesting they struggle more with mental tiredness.

Cognitive Impairment
E2 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

Brain MRI abnormalities exist in a subset of patients with chronic fatigue syndrome.

Lange, G, DeLuca, J, Maldjian, J A et al.·Journal of the neurological sciences·1999

Researchers used brain MRI scans to look for abnormalities in people with ME/CFS and compared them to healthy controls. They found that some ME/CFS patients—specifically those without a separate psychiatric diagnosis—had small spots of unusual tissue in the white matter of their brains, mostly in the frontal lobes (the front part of the brain). These brain changes were not found in healthy people or in ME/CFS patients who also had psychiatric diagnoses.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Attention and information processing efficiency in patients with Chronic Fatigue Syndrome.

Michiels, V, de Gucht, V, Cluydts, R et al.·Journal of clinical and experimental neuropsychology·1999

This study tested thinking and memory skills in 29 people with ME/CFS and compared them to 22 healthy people of similar age and education. The results showed that people with ME/CFS had slower thinking speed and difficulty processing information efficiently, but their ability to shift attention or focus on specific visual tasks was not notably impaired. Interestingly, memory problems appeared to stem from difficulty storing new information initially, rather than trouble recalling it later.

Cognitive Impairment
E2 ModeratePEM unclearModerate confidenceLongitudinalEditor reviewed

Prognostic factors for persons with idiopathic chronic fatigue.

Hartz, A J, Kuhn, E M, Bentler, S E et al.·Archives of family medicine·1999

This study followed 199 people with chronic fatigue for 2 years to understand which factors predicted who would improve. Researchers found that people who had clearer thinking, fewer additional symptoms, better sleep patterns, and were married tended to show the most improvement in fatigue. Interestingly, when patients improved in other symptoms like depression, muscle pain, or sleep problems, their fatigue also tended to improve together.

SleepCognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Relation between neuropsychological impairment and functional disability in patients with chronic fatigue syndrome.

Christodoulou, C, DeLuca, J, Lange, G et al.·Journal of neurology, neurosurgery, and psychiatry·1998

This study looked at whether memory and attention problems in ME/CFS patients are linked to how much their daily activities are limited. Researchers tested 53 ME/CFS patients and 32 healthy people on memory and concentration, and found that patients with more failing test scores reported spending significantly more days inactive. Importantly, this connection held true even when accounting for depression, suggesting the cognitive problems themselves—not just mood—contribute to disability.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Evaluating neuropsychological impairment in chronic fatigue syndrome.

Vercoulen, J H, Bazelmans, E, Swanink, C M et al.·Journal of clinical and experimental neuropsychology·1998

This study looked at whether people with ME/CFS have problems with thinking, memory, and concentration. Researchers tested patients using standard cognitive tests and also asked them to report their own memory and concentration difficulties. Surprisingly, most patients performed normally on the tests, and there was no clear connection between test results and what patients reported experiencing in daily life.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Exploring the validity of the Chalder Fatigue scale in chronic fatigue syndrome.

Morriss, R K, Wearden, A J, Mullis, R·Journal of psychosomatic research·1998

This study tested whether the Chalder Fatigue Scale—a common questionnaire used to measure tiredness in ME/CFS patients—actually measures what it claims to measure. Researchers analyzed responses from 136 ME/CFS patients and found that fatigue has four distinct components: mental tiredness (linked to thinking problems), sleep difficulties, physical weakness (linked to low fitness), and depression. The results suggest the 11-item version of the scale works better than the original 14-item version for measuring fatigue in ME/CFS.

SleepCognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Impaired associative learning in chronic fatigue syndrome.

Servatius, R J, Tapp, W N, Bergen, M T et al.·Neuroreport·1998

This study tested whether people with ME/CFS have problems with how their brain learns and forms connections between different pieces of information. Researchers measured brain learning using a test where a gentle puff of air is paired with an eye blink stimulus. While ME/CFS patients could hear and feel the stimuli normally, they had difficulty learning to associate the two stimuli together—suggesting their brain's ability to form certain types of connections may be affected.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Attention and verbal learning in patients with chronic fatigue syndrome.

Michiels, V, Cluydts, R, Fischler, B·Journal of the International Neuropsychological Society : JINS·1998

This study tested thinking and memory skills in 20 people with ME/CFS and compared them to 22 healthy people. The researchers found that people with ME/CFS had difficulty with attention tasks that required handling multiple pieces of information at once, and they performed worse on remembering spoken information. However, their ability to focus on a single thing while ignoring distractions appeared to work normally.

Cognitive Impairment
E2 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

Patients with chronic fatigue syndrome and accurate feeling-of-knowing judgments.

Lakein, D A, Fantie, B D, Grafman, J et al.·Journal of clinical psychology·1997

Many people with ME/CFS say they have memory problems, but doctors have had trouble proving this in tests. This study looked at whether the issue might be that ME/CFS patients are bad at judging how confident they should be about their memories. When researchers tested both ME/CFS patients and healthy people on a trivia quiz, they found that both groups were equally good at knowing when they probably got an answer right—even though the ME/CFS patients reported much worse fatigue and cognitive symptoms.

Cognitive Impairment
E2 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

Neuropsychological and psychological functioning in chronic fatigue syndrome.

Kane, R L, Gantz, N M, DiPino, R K·Neuropsychiatry, neuropsychology, and behavioral neurology·1997

This study compared 17 people with ME/CFS to 17 healthy controls on thinking and memory tests, as well as psychological well-being. While ME/CFS patients reported feeling cognitively foggy, most formal test scores were similar between groups. However, ME/CFS patients showed significantly higher levels of psychological distress, anxiety, and depression compared to controls.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Cognitive functioning is impaired in patients with chronic fatigue syndrome devoid of psychiatric disease.

DeLuca, J, Johnson, S K, Ellis, S P et al.·Journal of neurology, neurosurgery, and psychiatry·1997

This study tested thinking and memory skills in people with ME/CFS and found they performed worse than healthy people, even among those without depression or anxiety. The cognitive problems—like difficulty concentrating, remembering things, and processing information—appear to be a direct part of ME/CFS itself, not caused by mental health conditions. This suggests the 'brain fog' many ME/CFS patients experience is a real biological feature of the illness.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Cognitive performance and complaints of cognitive impairment in chronic fatigue syndrome (CFS).

Wearden, A, Appleby, L·Psychological medicine·1997

This study asked people with ME/CFS about memory and concentration problems and then tested them in the lab. While ME/CFS patients reported more trouble concentrating and remembering when reading compared to healthy people, standard lab tests didn't always show measurable differences—except in those with depression. This suggests that cognitive difficulties in ME/CFS may be real but show up more in everyday activities than in controlled lab settings.

Cognitive Impairment
E2 ModeratePEM unclearPreliminaryCross-SectionalEditor reviewed

Sudden vs gradual onset of chronic fatigue syndrome differentiates individuals on cognitive and psychiatric measures.

DeLuca, J, Johnson, S K, Ellis, S P et al.·Journal of psychiatric research·1997

This study looked at whether the way ME/CFS starts—suddenly or gradually—affects thinking abilities and mental health. Researchers tested 36 ME/CFS patients on memory, concentration, and processing speed, and compared them to healthy controls. They found that people whose ME/CFS came on gradually were more likely to have depression or anxiety, while those with sudden onset had more severe memory problems.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Cognitive deficits in patients suffering from chronic fatigue syndrome, acute infective illness or depression.

Vollmer-Conna, U, Wakefield, D, Lloyd, A et al.·The British journal of psychiatry : the journal of mental science·1997

This study tested how well people with ME/CFS could think and concentrate compared to people with depression, acute infections, and healthy people. All three patient groups performed worse on attention and memory tests and reported feeling more tired than healthy controls. Importantly, people with ME/CFS and acute infection had less severe mood problems than those with depression, suggesting their cognitive difficulties aren't simply caused by depression.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Cognitive functioning in patients with chronic fatigue syndrome.

Michiels, V, Cluydts, R, Fischler, B et al.·Journal of clinical and experimental neuropsychology·1996

This study found that people with ME/CFS performed worse than healthy controls on thinking and memory tests. Patients showed slower processing speed, difficulty concentrating, and trouble learning and remembering new information. However, the researchers noted that cognitive problems varied widely between patients, so not everyone with ME/CFS experiences the same level of difficulty.

Cognitive Impairment
E2 ModeratePEM unclearModerate confidenceCross-SectionalEditor reviewed

Selective impairment of auditory processing in chronic fatigue syndrome: a comparison with multiple sclerosis and healthy controls.

Johnson, S K, DeLuca, J, Diamond, B J et al.·Perceptual and motor skills·1996

This study tested whether people with ME/CFS have trouble processing sounds specifically, or if they struggle with processing information in general. Researchers compared people with ME/CFS, people with multiple sclerosis, and healthy people on two similar tasks—one using sounds and one using visuals. People with ME/CFS performed worse on the sound-based task but did better on the visual task, suggesting their brains may have particular difficulty processing auditory information.

Cognitive Impairment
E2 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

Comparison of 99m Tc HMPAO SPECT scan between chronic fatigue syndrome, major depression and healthy controls: an exploratory study of clinical correlates of regional cerebral blood flow.

Fischler, B, D'Haenen, H, Cluydts, R et al.·Neuropsychobiology·1996

This study used a brain imaging technique called SPECT scans to compare blood flow in the brains of people with ME/CFS, people with depression, and healthy volunteers. Researchers found that in ME/CFS patients, blood flow in the front part of the brain was connected to cognitive problems and physical activity limitations. Unlike depression, ME/CFS did not show overall reduced blood flow in the brain, but did show a specific pattern of asymmetry (one side different from the other) in the side-back regions.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Memory, attention, and executive function in chronic fatigue syndrome.

Joyce, E, Blumenthal, S, Wessely, S·Journal of neurology, neurosurgery, and psychiatry·1996

This study compared the thinking abilities of 20 people with ME/CFS to 20 healthy controls using computerized tests and word tasks. Researchers found that ME/CFS patients had difficulty with memory tasks that required effort and attention, especially when they had to actively retrieve or organize information themselves. However, their problems were different from those seen in dementia or stroke-related memory loss, and they performed normally on simpler memory tests.

Cognitive Impairment
E2 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

Cognitive idiosyncrasies among children with the chronic fatigue syndrome: anomalies in self-reported activity levels.

Fry, A M, Martin, M·Journal of psychosomatic research·1996

This study looked at whether children with ME/CFS and their parents perceive their activity levels differently than healthy children do. Researchers used activity monitors (objective measurement) and asked children and parents to estimate activity (subjective measurement) over 3 days. They found that children with ME/CFS and their parents underestimated how much activity was actually happening, and there was a bigger gap between what they expected to do in the future versus what they wanted to do.

Cognitive Impairment
E2 ModeratePEM unclearModerate confidenceCross-SectionalEditor reviewed

Neuropsychological impairments in chronic fatigue syndrome, multiple sclerosis, and depression.

DeLuca, J, Johnson, S K, Beldowicz, D et al.·Journal of neurology, neurosurgery, and psychiatry·1995

This study tested thinking and memory skills in people with ME/CFS, comparing them to people with multiple sclerosis, depression, and healthy individuals. Researchers found that people with ME/CFS had significant trouble processing information quickly, similar to those with depression. The cognitive problems in ME/CFS were not explained by depression or anxiety alone.

Cognitive Impairment
E2 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

P300 assessment of chronic fatigue syndrome.

Polich, J, Moore, A P, Wiederhold, M D·Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society·1995

This study measured electrical activity in the brains of people with ME/CFS and healthy controls using a simple listening task where they had to identify specific sounds. Researchers found no differences in brain wave patterns (called P300) between the two groups, even though many ME/CFS patients report problems with memory and attention. This suggests that brain electrical activity measured this way may not be a reliable marker for ME/CFS.

Cognitive Impairment
E2 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

Cognitive functioning in chronic fatigue syndrome and depression: a preliminary comparison.

Schmaling, K B, DiClementi, J D, Cullum, C M et al.·Psychosomatic medicine·1994

Researchers tested thinking and memory skills in 16 people with ME/CFS and 23 people with depression using a brief set of mental tests. Both groups performed similarly to each other and scored in the normal range on most tests. Interestingly, people with ME/CFS reported more cognitive problems than their test scores showed, which the researchers suggest might be due to increased attention to physical sensations rather than actual cognitive damage.

Cognitive Impairment
E2 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

Dimensional assessment of chronic fatigue syndrome.

Vercoulen, J H, Swanink, C M, Fennis, J F et al.·Journal of psychosomatic research·1994

This study asked 298 people with ME/CFS to fill out detailed questionnaires about how the illness affected them. Researchers found that ME/CFS affects people in nine different ways: mood and emotional health, ability to do daily activities, sleep quality, physical avoidance, thinking and memory problems, beliefs about what caused their illness, relationships and social life, confidence in their own abilities, and overall life satisfaction. Understanding these separate aspects could help doctors better assess and treat ME/CFS in individual patients.

SleepCognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Psychosocial correlates of illness burden in chronic fatigue syndrome.

Antoni, M H, Brickman, A, Lutgendorf, S et al.·Clinical infectious diseases : an official publication of the Infectious Diseases Society of America·1994

This study looked at how thoughts, feelings, and coping strategies affect how sick ME/CFS patients feel and function day-to-day. Researchers found that negative thinking patterns and avoidance-based coping (like denial) were linked to worse symptoms and lower quality of life, while active problem-solving strategies did not improve outcomes. These relationships held true whether or not patients also had depression.

Cognitive Impairment
E2 ModeratePEM unclearModerate confidenceCross-SectionalEditor reviewed

Quality of attention in chronic fatigue syndrome: subjective reports of everyday attention and cognitive difficulty, and performance on tasks of focused attention.

Ray, C, Phillips, L, Weir, W R·The British journal of clinical psychology·1993

Many people with ME/CFS report problems with attention and concentration in daily life. This study compared ME/CFS patients with healthy people using questionnaires about attention problems and computer-based attention tests. Patients reported significantly more attention difficulties than controls, though standard attention tests didn't show clear differences. Interestingly, patients were slower at processing tasks like reading words and naming colors, suggesting their thinking speed may be affected rather than their ability to focus.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Behavioural problems associated with the chronic fatigue syndrome.

Smith, A P, Behan, P O, Bell, W et al.·British journal of psychology (London, England : 1953)·1993

This study tested whether people with ME/CFS actually experience the memory, concentration, and coordination problems they report. Researchers gave 57 ME/CFS patients and 19 healthy controls a series of computerized tests measuring thinking speed, memory, attention, and motor skills. ME/CFS patients performed worse on many tests—they were slower at tasks requiring coordination, had trouble focusing, and struggled with complex reasoning—even though their depression and anxiety levels didn't fully explain these differences.

Cognitive Impairment
E2 ModeratePEM unclearModerate confidenceCase-ControlEditor reviewed

Information processing efficiency in chronic fatigue syndrome and multiple sclerosis.

DeLuca, J, Johnson, S K, Natelson, B H·Archives of neurology·1993

This study compared thinking and concentration abilities in people with ME/CFS, people with multiple sclerosis (MS), and healthy volunteers. All participants were matched by age and education level. People with ME/CFS and MS both showed difficulty with tasks requiring fast, complex thinking compared to healthy controls, suggesting that ME/CFS may affect how the brain processes information.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Fatigue, depression, and social adjustment in chronic fatigue syndrome.

Walford, G A, Nelson, W M, McCluskey, D R·Archives of disease in childhood·1993

This study looked at 12 children with ME/CFS and compared them to children with cystic fibrosis and healthy children. Children with ME/CFS reported much higher levels of tiredness affecting both body and mind, and many showed signs of depression. Their schooling and social lives were seriously disrupted by the illness.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

A brief mental fatigue questionnaire.

Bentall, R P, Wood, G C, Marrinan, T et al.·The British journal of clinical psychology·1993

Researchers created a short questionnaire to measure mental tiredness and tested it in people with ME/CFS, depression, recovered ME/CFS, muscle disease, and healthy people. The questionnaire worked well at identifying mental fatigue, but it could not tell the difference between people with ME/CFS and people with depression—both groups reported similar types and amounts of mental tiredness.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Illness perception and symptom components in chronic fatigue syndrome.

Ray, C, Weir, W R, Cullen, S et al.·Journal of psychosomatic research·1992

This study asked 208 people with ME/CFS about their symptoms and how they experience their illness. Researchers found that ME/CFS involves four main types of problems: emotional distress, fatigue, physical symptoms, and difficulty thinking clearly. Emotional distress did not directly determine how sick people felt overall, but negative emotions did make the other symptoms worse.

Cognitive Impairment
E2 ModeratePEM not requiredPreliminaryCase-ControlEditor reviewed

Attention and short-term memory in chronic fatigue syndrome patients: an event-related potential analysis.

Scheffers, M K, Johnson, R, Grafman, J et al.·Neurology·1992

This study compared brain activity and reaction times between 13 people with ME/CFS and 13 healthy volunteers using brain scans while they performed attention and memory tasks. The ME/CFS patients showed much slower and more variable reaction times, but their memory and thinking abilities appeared normal. The researchers found that the brain's basic attention and memory processes were working similarly in both groups, suggesting the slowness came from problems with how the brain signals muscles to respond.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Characterization of Postural Orthostatic Tachycardia Syndrome in Long COVID: Self-reported Data From the LISTEN Study.

Al Mouslmani, Mohammad, Sawano, Mitsuaki, Arun, Adith S et al.·JACC. Advances·2025

This study looked at people with long COVID who also developed POTS (a condition where the heart rate spikes when standing up). Among nearly 600 long COVID patients, about 29% reported having POTS. People with both conditions reported significantly more symptoms—including dizziness, chest pain, extreme fatigue, difficulty exercising, and brain fog—and experienced worse overall health and quality of life compared to those with long COVID alone.

Autonomic Nervous SystemCognitive Impairment
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Prevalence and severity of neurologic symptoms in Long-COVID and the role of pre-existing conditions, hospitalization, and mental health.

Huff, Hanalise V, Roberts, Henry, Bartrum, Elizabeth et al.·Frontiers in neurology·2025

This study looked at neurological symptoms in 213 people with Long-COVID, examined 8 months after infection. Researchers found that fatigue, brain fog, unrefreshed sleep, and word-finding difficulties were very common and often severe. Importantly, these symptoms appeared to be caused by the virus itself rather than by pre-existing health conditions or how sick people were during acute infection.

Cognitive Impairment
E2 ModeratePEM unclearPreliminaryObservationalEditor reviewed

Low-dose Naltrexone Improves post-COVID-19 condition Symptoms.

Tamariz, Leonardo, Bast, Elizabeth, Klimas, Nancy et al.·Clinical therapeutics·2024

This study looked at whether treatments used for ME/CFS could help people with long COVID. Researchers reviewed records from 108 patients who tried different treatments including low-dose naltrexone, amitriptyline, duloxetine, and physical therapy. They found that patients taking low-dose naltrexone were about 5 times more likely to improve compared to those doing physical therapy alone, with improvements in both fatigue and pain.

Pain and SensitizationCognitive Impairment
E2 ModeratePEM unclearModerate confidenceCross-SectionalEditor reviewed

Phase-dependent trends in the prevalence of myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) related to long COVID: A criteria-based retrospective study in Japan.

Morita, Satoru, Tokumasu, Kazuki, Otsuka, Yuki et al.·PloS one·2024

This study looked at 739 patients with long COVID to understand how many developed ME/CFS and what factors were involved. Researchers found that ME/CFS affected about 8% of long COVID patients, but the rate varied depending on which COVID variant caused the initial infection—it was much higher (24%) in early COVID but dropped significantly (3%) during the Omicron wave. Brain fog complaints increased over time, even as strict ME/CFS diagnoses became less common.

Cognitive Impairment
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[The Significance of Chronic Fatigue in the Post-Covid Consultation and its Consequences for Outpatient Rehabilitation in the Context of Statutory Accident Insurance].

Dalichau, Stefan, Kordy, Henrike, Klüver, Janna et al.·Psychotherapie, Psychosomatik, medizinische Psychologie·2024

This study looked at 454 people (mostly women aged 40–60) who developed long-term fatigue after COVID-19. Nearly all of them reported severe tiredness, and over 73% also experienced brain fog. The fatigue lasted about 14–15 months on average and significantly affected their ability to work and enjoy daily life. The researchers recommend that treatment should focus on managing chronic fatigue similar to ME/CFS, using education and practical coping strategies rather than trying to 'cure' the condition.

Cognitive Impairment
E2 ModeratePEM unclearModerate confidenceCase-ControlEditor reviewed

A case-control study of reaction time deficits in a 3D virtual reality in patients with Post-COVID syndrome.

Güttes, Moritz, Lucio, Marianna, Skornia, Adam et al.·Scientific reports·2024

Researchers tested whether people with Post-COVID syndrome have slower reaction times when responding to visual stimuli shown in virtual reality glasses. They found that Post-COVID patients were indeed slower and less accurate at this task compared to healthy controls, suggesting this test might be a useful tool for identifying Post-COVID cognitive problems in the future.

Cognitive Impairment
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The association between the number of symptoms and the severity of Post-COVID-Fatigue after SARS-CoV-2 infection treated in an outpatient setting.

Schmidbauer, Lena, Kirchberger, Inge, Goßlau, Yvonne et al.·Journal of neurology·2023

This study looked at 425 people who had mild-to-moderate COVID-19 treated as outpatients and followed them for about 8 months afterward. Researchers found that 37% of these people developed long-lasting fatigue (Post-COVID-Fatigue), and those who had more symptoms during their initial infection and ongoing symptoms were more likely to experience severe fatigue. The more symptoms someone had, the worse their fatigue tended to be.

Cognitive Impairment
E2 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

Investigating brain cortical activity in patients with post-COVID-19 brain fog.

Wojcik, Grzegorz M, Shriki, Oren, Kwasniewicz, Lukasz et al.·Frontiers in neuroscience·2023

This study looked at brain electrical activity in people who had COVID-19 and experienced 'brain fog'—persistent mental cloudiness that can last several months. Researchers compared three groups using advanced brain scans while people performed thinking tasks, and used computer algorithms to see if they could distinguish between those with brain fog, those without it, and healthy controls. They found measurable differences in brain activity patterns between the groups, suggesting brain fog has a detectable physical basis in the brain.

Cognitive Impairment
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Post-acute sequelae of COVID-19 in young adults: Mental fatigue and decreased cognitive flexibility.

Sedat, Yasin, Erman, Altunisik, Yasemin, Firat Ekmekyapar·Ideggyogyaszati szemle·2023

This study looked at young adults who had COVID-19 and compared them to those who hadn't. Researchers found that people who had COVID-19 reported more mental fatigue (difficulty concentrating and feeling mentally tired) and had more trouble switching between different tasks. These problems lasted long after the initial infection, suggesting COVID-19 may have lasting effects on how the brain works.

Cognitive Impairment
E2 ModeratePEM unclearPreliminaryObservationalEditor reviewed

Epipharyngeal Abrasive Therapy (EAT) Has Potential as a Novel Method for Long COVID Treatment.

Imai, Kazuaki, Yamano, Takafumi, Nishi, Soichiro et al.·Viruses·2022

This study tested a Japanese treatment called epipharyngeal abrasive therapy (EAT) on 58 long COVID patients. The treatment involves applying zinc chloride to the back of the throat to reduce inflammation. Patients received weekly treatments for one month, and three common symptoms—fatigue, headaches, and difficulty concentrating—improved significantly after treatment.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Post-acute sequelae of SARS-CoV-2 infection: relationship of central nervous system manifestations with physical disability and systemic inflammation.

Busatto, Geraldo F, de Araujo, Adriana Ladeira, Castaldelli-Maia, João Mauricio et al.·Psychological medicine·2022

Researchers studied 749 people who had been hospitalized with COVID-19 and assessed them 6-11 months later. They found that 30 different symptoms—including fatigue, brain fog, depression, and anxiety—tend to occur together as part of one underlying condition. People with more severe symptoms also showed signs of ongoing inflammation in their blood and had greater physical disability, suggesting a real biological basis for their illness.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceLongitudinalEditor reviewed

Chronic fatigue syndrome and cognitive deficit are associated with acute-phase neuropsychiatric manifestations of COVID-19: A 9-month follow-up study.

Mirfazeli, Fatemeh Sadat, Sarabi-Jamab, Atiye, Pereira-Sanchez, Victor et al.·Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·2022

This study followed 95 COVID-19 patients for 9 months to see which ones developed long-COVID symptoms like fatigue and brain fog. The most common symptom was extreme tiredness (affecting about half the patients), followed by anxiety, shortness of breath, and headaches. Interestingly, how sick someone was during acute COVID didn't predict whether they'd have long-COVID problems—but certain early warning signs (like psychiatric symptoms during the acute phase) did predict who would develop chronic fatigue and memory problems later.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceObservationalEditor reviewed

Incidence of post-COVID syndrome and associated symptoms in outpatient care in Bavaria, Germany: a retrospective cohort study using routinely collected claims data.

Donnachie, Ewan, Hapfelmeier, Alexander, Linde, Klaus et al.·BMJ open·2022

This study looked at health insurance records from nearly 400,000 people in Germany who had COVID-19 to see how many developed long COVID symptoms lasting at least 12 weeks. About 14% of COVID-19 patients received a diagnosis of post-COVID syndrome, with the most common symptoms being fatigue, breathing problems, and loss of taste or smell. These symptoms occurred much more often in COVID-19 patients compared to people who had other respiratory infections or no respiratory illness.

Cognitive Impairment
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Characteristics of Sleep Disturbance in Patients with Long COVID: A Retrospective Observational Study in Japan.

Sunada, Naruhiko, Nakano, Yasuhiro, Otsuka, Yuki et al.·Journal of clinical medicine·2022

This study looked at sleep problems in 363 long COVID patients in Japan and found that about 16.5% had significant sleep disturbance. People infected during the Omicron wave were twice as likely to have sleep problems compared to those infected during the Delta wave. Patients with sleep disturbance also reported more fatigue, brain fog, headaches, and anxiety, and had abnormal stress hormone levels suggesting their bodies were under persistent stress.

SleepCognitive Impairment
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Neurocognitive screening in patients following SARS-CoV-2 infection: tools for triage.

Blackmon, Karen, Day, Gregory S, Powers, Harry Ross et al.·BMC neurology·2022

Many people recovering from COVID-19 report trouble thinking clearly or remembering things. This study tested 102 COVID-19 patients (some who were hospitalized, some who weren't) within about 3-4 weeks of infection to see how common these cognitive problems really were and what might cause them. The researchers found that while most patients felt foggy-headed, people who had been hospitalized showed more measurable problems with memory and thinking speed than those who recovered at home.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceObservationalEditor reviewed

Evolving phenotypes of non-hospitalized patients that indicate long COVID.

Estiri, Hossein, Strasser, Zachary H, Brat, Gabriel A et al.·BMC medicine·2021

This study looked at medical records from over 96,000 people to identify which health problems are more common in people who had COVID-19 compared to those who didn't. Researchers found that certain symptoms and conditions—including loss of taste and smell, hair loss, chest pain, extreme tiredness, shortness of breath, pneumonia, and new-onset diabetes—appear more frequently in COVID-19 survivors months after infection. Younger people under 65 developed more of these long-term problems than older adults.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Disentangling comorbidity: symptom dimensions of internalizing and functional disorders in a large general population sample.

Saini, Urvi, Aggen, Steven H, Oldehinkel, Albertine J et al.·BMC psychiatry·2026

This study looked at how symptoms of depression, anxiety, ME/CFS, fibromyalgia, and irritable bowel syndrome overlap in over 100,000 people. Researchers found that these conditions share common symptoms like fatigue, sleep problems, and difficulty concentrating—which they call 'general malaise'—rather than being completely separate diseases. Understanding these shared symptoms may help explain why people often have multiple conditions at the same time.

Pain and SensitizationCognitive Impairment
E2 ModeratePEM unclearPreliminaryCross-SectionalEditor reviewed

Assessment of dynamic cerebral blood flow changes during cognitive tasks in patients with post-COVID-19 syndrome.

Kutz, Dieter F, Garbsch, René, Mooren, Frank C et al.·Brain communications·2026

This study looked at how blood flow in the brain changes when people with post-COVID-19 syndrome try to do mental tasks. Researchers used special infrared cameras to watch blood flow in the thinking part of the brain while patients did concentration exercises. They found that people with post-COVID-19 had unusual, less flexible blood flow patterns compared to healthy people, which may help explain why they feel mentally tired and have trouble concentrating.

Cognitive Impairment
E2 ModeratePEM unclearModerate confidenceLongitudinalEditor reviewed

Functional olfactory impairment and fatigue in post-COVID-19 syndrome including ME/CFS - a longitudinal prospective observational study.

Meyer-Arndt, Lil, Pierchalla, Greta, Mödl, Lukas et al.·Brain, behavior, & immunity - health·2025

This study followed 45 long-COVID patients over 28 months to understand the connection between smell problems and fatigue, including those who developed ME/CFS. Researchers tested how well patients could smell (detecting scent strength, telling scents apart, and identifying them) and measured their fatigue, thinking ability, and physical strength. Most patients' smell improved over time, but problems with identifying specific smells lasted the longest, and patients with better smell discrimination at the start tended to feel better and function better after 20 months.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceObservationalEditor reviewed

Identifying commonalities and differences between EHR representations of PASC and ME/CFS in the RECOVER EHR cohort.

Powers, John P, McIntee, Tomas J, Bhatia, Abhishek et al.·Communications medicine·2025

Researchers compared medical records from millions of patients to see how Long COVID (PASC) and ME/CFS are similar and different. They found that both conditions share common symptoms like fatigue, breathing difficulties, and trouble concentrating, but Long COVID tends to have more heart and lung problems, while ME/CFS more often involves pain and sleep issues. These similarities suggest that some treatment approaches might help both conditions.

Pain and SensitizationSleepCognitive Impairment
E2 ModeratePEM not requiredPreliminaryObservationalEditor reviewed

Nonpelvic comorbid symptoms of 45 patients with pain of pelvic venous origin, before and after treatment.

Smith, Steven J, Smith, B Holly, Sichlau, Michael J et al.·Phlebology·2025

This study looked at 45 women with chronic pelvic pain caused by abnormal blood pooling in pelvic veins. These patients experienced many symptoms beyond pelvic pain—including brain fog, fatigue, migraines, constipation, and anxiety. After receiving a catheter-based procedure to fix the blood pooling, most of these systemic symptoms improved significantly (by 50% or more).

Pain and SensitizationAutonomic Nervous SystemCognitive Impairment
E2 ModeratePEM unclearModerate confidenceCross-SectionalEditor reviewed

Assessing the Relationship in Symptomology of Myalgic Encephalitis/Chronic Fatigue Syndrome and Long COVID.

Garapaty, Nikitha, Reyes, Kristina M, Tehrani, Lily et al.·American journal of medicine open·2025

This study compared symptoms in people with ME/CFS, Long COVID, both conditions together, and people without either condition. Researchers found that people who have both ME/CFS and Long COVID experience the worst symptoms—including memory problems, anxiety, depression, fatigue, and difficulty exercising—compared to people with just one condition or neither. The findings suggest these two illnesses may interact in ways that make symptoms more severe when they occur together.

Cognitive Impairment
E2 ModeratePEM requiredPreliminaryCross-SectionalEditor reviewed

Exploratory study on autoantibodies to arginine-rich human peptides mimicking Epstein-Barr virus in women with post-COVID and myalgic encephalomyelitis/chronic fatigue syndrome.

Hoheisel, Friederike, Fleischer, Kathrin Maria, Rubarth, Kerstin et al.·Frontiers in immunology·2025

This study looked for certain antibodies in the blood of women with post-COVID and ME/CFS that might mistakenly attack the body's own proteins. The researchers found that patients with these conditions had more of these problematic antibodies than healthy people, and these antibodies were linked to common ME/CFS symptoms like fatigue, brain fog, pain, and autonomic problems. The results suggest that a virus (EBV) may trigger the immune system to attack human proteins that look similar to viral proteins.

Pain and SensitizationAutonomic Nervous SystemCognitive Impairment
E2 ModeratePEM unclearModerate confidenceCross-SectionalEditor reviewed

Hippocampal subfield volume alterations and associations with severity measures in long COVID and ME/CFS: A 7T MRI study.

Thapaliya, Kiran, Marshall-Gradisnik, Sonya, Eaton-Fitch, Natalie et al.·PloS one·2025

Researchers used advanced brain imaging to compare a part of the brain called the hippocampus in long COVID patients, ME/CFS patients, and healthy people. They found that certain areas of the hippocampus were larger in both patient groups compared to healthy controls, and these size differences were linked to how severe symptoms like fatigue, pain, and memory problems were. This suggests that changes in brain structure might explain some of the cognitive difficulties these patients experience.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Network structure of functional somatic symptoms.

Litzenburger, Alexandra, Rothacher, Yannick, Hanusch, Kay-Uwe et al.·Journal of psychosomatic research·2025

This study looked at how symptoms cluster together in people with functional somatic syndromes (like ME/CFS, fibromyalgia, and others). Researchers surveyed over 3,000 young adults and used network analysis to map which symptoms tend to appear together. They found that fatigue and depression are particularly important symptoms that connect different symptom groups, and identified ten distinct clusters of related symptoms.

Pain and SensitizationCognitive Impairment
E2 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

Brain Fog in Gastrointestinal Disorders: Small Intestinal Bacterial Overgrowth, Gastroparesis, Irritable Bowel Syndrome.

El Halabi, Maan, Arwani, Remy, Rao, Satish C et al.·Journal of clinical gastroenterology·2025

This study looked at brain fog—difficulty concentrating, remembering things, and thinking clearly—in patients with common digestive problems. Researchers surveyed 102 patients undergoing breath tests for bacterial overgrowth and found that over half reported brain fog. Those taking probiotics or with gastroparesis (slow stomach emptying) or irritable bowel syndrome were more likely to have brain fog.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceEditor reviewed

Two neurocognitive domains identified for patients with myalgic encephalomyelitis/chronic fatigue syndrome and post-acute sequelae of COVID-19.

Sandoval, Ariadna, Li, Mingqi, Jason, Leonard A·Frontiers in neurology·2025

This study looked at brain-related symptoms in over 2,600 people with ME/CFS and COVID long-haul (PASC), finding that their cognitive problems fall into two main categories. The first group includes classic memory and concentration difficulties, while the second group involves being overwhelmed by sensory input like loud noises or bright lights. The research suggests that doctors and researchers should pay more attention to sensory overload as an important part of cognitive problems in these conditions.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Connecting the dots: Network structures of internalizing and functional symptoms in a population-based cohort.

Saini, Urvi, Rosmalen, Judith G M, Oldehinkel, Albertine J et al.·Journal of psychosomatic research·2024

This study looked at how symptoms of depression, anxiety, ME/CFS, fibromyalgia, and irritable bowel syndrome are connected in over 70,000 people. Researchers found that these conditions tend to cluster separately, but are linked together through specific 'bridge' symptoms like fatigue, difficulty concentrating, and sleep problems. This helps explain why people often experience multiple conditions at the same time.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

The presence of attentional and interpretation biases in patients with severe MS-related fatigue.

de Gier, Marieke, Oosterman, Joukje M, Hughes, Alicia M et al.·British journal of health psychology·2024

This study looked at whether people with severe fatigue from MS or ME/CFS tend to notice fatigue-related information more readily or interpret unclear physical symptoms in a threatening way compared to healthy people. Researchers found that both MS and ME/CFS patients interpreted ambiguous body sensations as more threatening than healthy controls did, though there was no difference in how they paid attention to fatigue-related words. The way patients interpreted symptoms was linked to how they mentally responded to their symptoms.

Cognitive Impairment
E2 ModeratePEM unclearModerate confidenceCross-SectionalEditor reviewed

Stroop task and practice effects demonstrate cognitive dysfunction in long COVID and myalgic encephalomyelitis / chronic fatigue syndrome.

Baraniuk, James N, Thapaliya, Kiran, Inderyas, Maira et al.·Scientific reports·2024

This study tested how quickly people with Long COVID and ME/CFS could complete a simple task involving reading color words displayed in different colored inks. Both patient groups were noticeably slower at this task than healthy people, and unlike healthy people, they didn't get faster with practice. This suggests that ME/CFS and Long COVID may involve a problem with how different parts of the brain communicate during problem-solving.

Cognitive Impairment
E2 ModeratePEM unclearModerate confidenceRegistry-ResourceEditor reviewed

Longterm course of neuropsychological symptoms and ME/CFS after SARS-CoV-2-infection: a prospective registry study.

Reuken, P A, Besteher, B, Finke, K et al.·European archives of psychiatry and clinical neuroscience·2024

This study followed over 1,000 people who had long-lasting symptoms after COVID-19 infection. Researchers found that about 31% of patients met the diagnostic criteria for ME/CFS at their first visit, but this dropped to 19% at a second visit months later. While patients reported feeling less fatigued and having fewer concentration problems over time, many continued to experience long-lasting symptoms that significantly affected their daily lives.

Cognitive ImpairmentLong COVID Overlap
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Dysautonomia and small fiber neuropathy in post-COVID condition and Chronic Fatigue Syndrome.

Azcue, N, Del Pino, R, Acera, M et al.·Journal of translational medicine·2023

This study compared how the nervous system works differently in people with ME/CFS, people with long COVID, and healthy people. Researchers tested heart rate responses, sweating patterns, and how nerves respond to temperature. They found that people with ME/CFS had more severe problems with heart rate regulation and nerve fiber damage than those with long COVID, and both groups had more problems than healthy controls.

Autonomic Nervous SystemCognitive Impairment
E2 ModeratePEM unclearPreliminaryObservationalEditor reviewed

Physical Activity Effects on Muscle Fatigue in Sport in Active Adults with Long COVID-19: An Observational Study.

Coscia, Francesco, Mancinelli, Rosa, Gigliotti, Paola Virginia et al.·Diagnostics (Basel, Switzerland)·2023

This study looked at how physical activity affected fatigue and other symptoms in people with Long COVID-19. Researchers compared people who stayed active with those who were sedentary and tracked their symptoms over 6 to 12 months. They found that people who remained physically active experienced a larger drop in fatigue over time compared to those who were inactive, though both groups still had muscle weakness and sleep problems.

SleepCognitive Impairment
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A comparison of pain, fatigue, and function between post-COVID-19 condition, fibromyalgia, and chronic fatigue syndrome: a survey study.

Haider, Saman, Janowski, Adam J, Lesnak, Joseph B et al.·Pain·2023

This study surveyed 707 people with post-COVID-19, fibromyalgia, and/or ME/CFS to compare their symptoms. Researchers found that all three conditions share similar patterns of pain, fatigue, brain fog, anxiety, and depression that impact daily life. People with post-COVID-19 reported somewhat less severe pain and fatigue than those with fibromyalgia or ME/CFS, but those with multiple diagnoses had worse symptoms overall.

Pain and SensitizationCognitive Impairment
E2 ModeratePEM unclearModerate confidenceObservationalEditor reviewed

Cognitive impairment in post-acute sequelae of COVID-19 and short duration myalgic encephalomyelitis patients is mediated by orthostatic hemodynamic changes.

Day, Heather, Yellman, Brayden, Hammer, Sarah et al.·Frontiers in neuroscience·2023

This study examined why people with ME/CFS and long COVID experience 'brain fog' and memory problems. Researchers tested how well people could think and remember before and after standing up quickly (which can make blood pressure drop). They found that people with these illnesses had more trouble thinking clearly after the standing test, and this was linked to unusual changes in their heart rate and blood pressure. The findings suggest that problems with blood flow to the brain during physical stress may be contributing to cognitive difficulties.

Autonomic Nervous SystemCognitive Impairment
E2 ModeratePEM unclearPreliminaryCross-SectionalEditor reviewed

Urine Metabolite Analysis to Identify Pathomechanisms of Long COVID: A Pilot Study.

Taenzer, Maja, Löffler-Ragg, Judith, Schroll, Andrea et al.·International journal of tryptophan research : IJTR·2023

This study examined urine samples from people with Long COVID and ME/CFS to look for chemical imbalances that might explain their symptoms. Researchers found that both groups had lower levels of certain amino acids and neurotransmitters (brain chemicals) compared to healthy people, particularly affecting energy production, mood, and sleep. These chemical signatures could potentially be used as simple urine tests to help doctors understand what is happening in patients and create personalized treatments.

SleepAutonomic Nervous SystemCognitive Impairment
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Orthostatic Challenge Causes Distinctive Symptomatic, Hemodynamic and Cognitive Responses in Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Vernon, Suzanne D, Funk, Sherlyn, Bateman, Lucinda et al.·Frontiers in medicine·2022

Researchers tested whether a simple 10-minute standing test (NASA Lean Test) could reveal problems in people with Long COVID and ME/CFS. The test made symptoms worse in both patient groups but not in healthy people, and caused measurable changes in blood pressure and thinking speed. This suggests the test could help doctors confirm what patients are experiencing and provide objective evidence of their condition.

Autonomic Nervous SystemDiagnosticsCognitive Impairment
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The Fatigue-Related Symptoms Post-Acute SARS-CoV-2: A Preliminary Comparative Study.

Thomas, Marie·International journal of environmental research and public health·2022

This study compared fatigue and related symptoms in 26 people experiencing Long COVID with two groups: people without fatigue and people with ME/CFS. The Long COVID group reported severe fatigue, brain fog, sleep problems, and difficulty concentrating—similar to what people with ME/CFS experience. The findings suggest Long COVID and ME/CFS may share some common features.

SleepCognitive Impairment
E2 ModeratePEM unclearModerate confidenceCross-SectionalEditor reviewed

Brain fog of post-COVID-19 condition and Chronic Fatigue Syndrome, same medical disorder?

Azcue, N, Gómez-Esteban, J C, Acera, M et al.·Journal of translational medicine·2022

This study compared brain fog and fatigue symptoms in people with ME/CFS and those recovering from COVID-19 to see if they might be the same condition triggered by different causes. Both groups showed similar problems with fatigue, sleep, and muscle pain, but people with ME/CFS had more severe cognitive difficulties like trouble concentrating and processing information. Interestingly, loss of smell that lasted a long time in COVID-19 patients appeared connected to their cognitive problems.

Cognitive Impairment
E2 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

Long COVID and chronic fatigue syndrome: A survey of elderly female survivors in Egypt.

Aly, Menna A E G, Saber, Heba G·International journal of clinical practice·2021

This study looked at 115 elderly women in Egypt who had recovered from COVID-19 to see if their lingering symptoms might lead to chronic fatigue syndrome (ME/CFS). Most women reported problems like fatigue, muscle pain, and sleep trouble after COVID, and the study found that stress, sadness, and poor sleep were most strongly linked to developing CFS-like symptoms. Only one person in the study actually met full criteria for probable CFS, but the researchers suggest doctors should watch for these warning signs in long COVID patients.

SleepCognitive Impairment
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Attentional Processing and Interpretative Bias in Functional Neurological Disorder.

Keynejad, Roxanne C, Fenby, Edward, Pick, Susannah et al.·Psychosomatic medicine·2020

This study looked at how people with ME/CFS and a related condition called functional neurological disorder (FND) process information and interpret bodily sensations differently than healthy people. Researchers gave participants three types of tests: one measuring whether they automatically notice illness-related information, another testing how well they can control their attention, and a third examining whether they interpret unclear bodily sensations as signs of illness. The findings suggest that both ME/CFS and FND involve similar difficulties with attention control and a tendency to interpret bodily sensations as illness-related.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Adolescent and parent factors related to fatigue in paediatric multiple sclerosis and chronic fatigue syndrome: A comparative study.

Carroll, Susan, Chalder, Trudie, Hemingway, Cheryl et al.·European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society·2019

This study compared teenagers with multiple sclerosis (MS) who experienced fatigue, teenagers with ME/CFS, and healthy teenagers to understand what factors contribute to severe fatigue. Researchers found that teenagers with MS who were fatigued and teenagers with ME/CFS had very similar patterns of fatigue and unhelpful thinking patterns about their symptoms, but teenagers with ME/CFS had normal brain function while those with MS had some cognitive difficulties. The study suggests that psychological approaches used successfully in ME/CFS might also help teenagers with MS who experience fatigue.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

A Concurrent Cognitive Task Does Not Perturb Quiet Standing in Fibromyalgia and Chronic Fatigue Syndrome.

Rasouli, Omid, Fors, Egil A, Vasseljen, Ottar et al.·Pain research & management·2018

This study examined how well people with ME/CFS and fibromyalgia can balance while standing still, and whether doing mental math at the same time makes balancing harder. Researchers found that both ME/CFS and fibromyalgia patients had slightly worse balance control than healthy people, but surprisingly, adding a math task didn't make their balance worse—unlike what researchers expected.

Cognitive Impairment
E2 ModeratePEM unclearModerate confidenceCross-SectionalEditor reviewed

Prevalence of and risk factors for severe cognitive and sleep symptoms in ME/CFS and MS.

Jain, Vageesh, Arunkumar, Amit, Kingdon, Caroline et al.·BMC neurology·2017

This study compared cognitive problems (like trouble concentrating and memory issues) and sleep difficulties in people with ME/CFS and people with MS. Researchers found that cognitive and sleep problems were much more common in ME/CFS patients—98% reported trouble concentrating, and 55% reported severe unrefreshing sleep. The study also identified that ME/CFS patients who were older, current smokers, or had lower incomes were more likely to experience severe symptoms.

SleepCognitive Impairment
E2 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

Brain 18F-FDG PET Metabolic Abnormalities in Patients with Long-Lasting Macrophagic Myofascitis.

Van Der Gucht, Axel, Aoun Sebaiti, Mehdi, Guedj, Eric et al.·Journal of nuclear medicine : official publication, Society of Nuclear Medicine·2017

This study used a special type of brain scan (PET imaging) to look for energy metabolism problems in the brains of people with macrophagic myofascitis, a condition involving immune cell buildup in muscles. Researchers found that MMF patients had lower energy use in multiple brain regions compared to healthy people, and this pattern was especially pronounced in patients who also had thinking and memory problems.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Fatigue in an adult attention deficit hyperactivity disorder population: A trans-diagnostic approach.

Rogers, Denise C, Dittner, Antonia J, Rimes, Katharine A et al.·The British journal of clinical psychology·2017

This study looked at fatigue in adults with ADHD and compared it to fatigue in people with ME/CFS and healthy people. Researchers found that adults with ADHD experience significantly more fatigue than healthy controls, with about 62% meeting criteria for clinically significant fatigue. Importantly, they discovered that people with ME/CFS and people with ADHD share many similar challenges, including low mood, anxiety, and reduced confidence in their abilities.

Cognitive Impairment
E2 ModeratePEM unclearModerate confidenceLongitudinalEditor reviewed

Neurocognitive complaints and functional status among patients with chronic fatigue syndrome and fibromyalgia.

Schmaling, Karen B, Betterton, Karran L·Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation·2016

This study followed 93 patients with ME/CFS over 18 months to understand how cognitive problems (like memory and perception difficulties) and physical function change over time. Patients who had both ME/CFS and fibromyalgia reported more pain, worse physical function, and more cognitive difficulties than those with ME/CFS alone. Interestingly, pain improved over time only for the ME/CFS-only group, suggesting that having both conditions may make recovery slower and more complicated.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

What is in a name? Comparing diagnostic criteria for chronic fatigue syndrome with or without fibromyalgia.

Meeus, Mira, Ickmans, Kelly, Struyf, Filip et al.·Clinical rheumatology·2016

This study compared people with ME/CFS to people with multiple sclerosis and healthy volunteers to see how sick they were and how well they could function. Researchers found that people with ME/CFS had worse physical abilities (like muscle strength and recovery), more severe symptoms, lower quality of life, and more difficulty with daily activities. They also discovered that when ME/CFS patients also had fibromyalgia (widespread pain), their overall symptom burden was much greater.

DiagnosticsCognitive Impairment
E2 ModeratePEM unclearModerate confidenceCross-SectionalEditor reviewed

Associations Between Cognitive Performance and Pain in Chronic Fatigue Syndrome: Comorbidity with Fibromyalgia Does Matter.

Ickmans, Kelly, Meeus, Mira, De Kooning, Margot et al.·Pain physician·2015

This study looked at whether pain and thinking problems are connected in people with ME/CFS, and whether having fibromyalgia alongside ME/CFS changes this relationship. Researchers tested 48 patients with ME/CFS (some with fibromyalgia, some without) and 30 healthy people on memory and attention tasks, then measured their pain responses. They found that the type of pain problem matters: in patients with both conditions, a specific pain-processing difference predicted thinking problems, while in ME/CFS-only patients, reported pain levels predicted thinking problems.

Pain and SensitizationCognitive Impairment
E2 ModeratePEM unclearModerate confidenceCross-SectionalEditor reviewed

[Impact of the fibromyalgia in the chronic fatigue syndrome].

Faro, Mónica, Sáez-Francàs, Naia, Castro-Marrero, Jesús et al.·Medicina clinica·2014

This study looked at nearly 1,000 ME/CFS patients to see how many also had fibromyalgia (a condition causing widespread pain and fatigue), and whether having both conditions made symptoms worse. They found that about half of the ME/CFS patients also had fibromyalgia, and those patients experienced higher levels of fatigue, pain, sleep problems, and cognitive difficulties. People with both conditions reported a much greater impact on their quality of life compared to those with ME/CFS alone.

SleepAutonomic Nervous SystemCognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Characterization of fatigue states in medicine and psychiatry by structured interview.

Bennett, Barbara Kaye, Goldstein, David, Chen, Michelle et al.·Psychosomatic medicine·2014

This study developed and tested a structured interview tool to help doctors better distinguish between different types of fatigue, including ME/CFS, fatigue after cancer treatment, and depression-related fatigue. Researchers interviewed women with different fatigue conditions and found the tool was very accurate at identifying ME/CFS and depression, though less reliable for cancer-related fatigue. The tool may help doctors more accurately diagnose why patients are experiencing fatigue.

DiagnosticsCognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

"Functional" or "psychosomatic" symptoms, e.g. a flu-like malaise, aches and pain and fatigue, are major features of major and in particular of melancholic depression.

Maes, Michael·Neuro endocrinology letters·2009

This study looked at whether depression and ME/CFS share similar physical symptoms like fatigue, muscle pain, and feeling like you have an infection. Researchers found that people with severe depression often experience these "body-centered" symptoms as a major part of their illness. The findings suggest that doctors should pay more attention to these physical symptoms when diagnosing and treating depression.

Pain and SensitizationCognitive Impairment
E2 ModeratePEM unclearPreliminaryObservationalEditor reviewed

Measuring health outcomes of a multidisciplinary care approach in individuals with chronic environmental conditions using an abbreviated symptoms questionnaire.

Fox, Roy, Sampalli, Tara, Fox, Jonathan·Journal of multidisciplinary healthcare·2008

This study looked at how well a multidisciplinary treatment program (combining different types of care) worked for people with multiple chemical sensitivity and related conditions like ME/CFS. Researchers tracked 292 patients over time and used a symptom questionnaire to measure improvement. They found that some symptoms like difficulty concentrating and tiredness improved quickly (within 6 months), while others like fatigue took longer to improve.

Cognitive Impairment
E2 ModeratePEM unclearPreliminaryCross-SectionalEditor reviewed

The experience of cancer-related fatigue and chronic fatigue syndrome: a qualitative and comparative study.

Bennett, Barbara, Goldstein, David, Friedlander, Michael et al.·Journal of pain and symptom management·2007

This study compared how fatigue affects women with cancer-related fatigue (after breast cancer treatment) versus women with ME/CFS. Both groups described very similar experiences: exhaustion, problems with thinking and memory, and mood changes. Women with ME/CFS also reported muscle pain and flu-like symptoms more often. The researchers found that these two conditions share a common set of disabling symptoms, suggesting they may involve similar underlying causes despite different triggers.

Cognitive Impairment
E2 ModeratePEM not requiredPreliminaryObservationalEditor reviewed

JP-8 jet fuel exposure and divided attention test performance in 1991 Gulf War veterans.

Bell, Iris R, Brooks, Audrey J, Baldwin, Carol M et al.·Aviation, space, and environmental medicine·2005

This study examined how exposure to low levels of jet fuel affected thinking and attention in Gulf War veterans who were chronically ill. Researchers tested veterans' reaction times on a computer task before and after brief exposures to either jet fuel fumes or clean air, done three times over three weeks. Veterans who were ill and had chemical sensitivities showed faster reaction times after jet fuel exposure, which the researchers suggest might indicate changes in brain chemistry rather than improved thinking.

Cognitive Impairment
E2 ModeratePEM unclearModerate confidenceCase-ControlEditor reviewed

Symptom factor analysis, clinical findings, and functional status in a population-based case control study of Gulf War unexplained illness.

Bourdette, D N, McCauley, L A, Barkhuizen, A et al.·Journal of occupational and environmental medicine·2001

Researchers surveyed over 2,000 Gulf War veterans and conducted detailed medical exams on 443 of them to look for unexplained health symptoms. They found that many veterans experienced overlapping symptoms—including cognitive problems, fatigue, and muscle pain—that resembled conditions like fibromyalgia and chronic fatigue syndrome, but they found few clear physical differences between sick and healthy veterans.

Pain and SensitizationCognitive Impairment
E2 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

Overlapping conditions among patients with chronic fatigue syndrome, fibromyalgia, and temporomandibular disorder.

Aaron, L A, Burke, M M, Buchwald, D·Archives of internal medicine·2000

This study found that ME/CFS, fibromyalgia, and temporomandibular disorder (TMD) often occur together in the same patients and share similar symptoms like pain, fatigue, and sleep problems. The researchers also discovered that patients with these conditions frequently experience other illnesses like irritable bowel syndrome and headaches—much more often than healthy people do. The study suggests these conditions may be connected in some way we don't yet fully understand.

Pain and SensitizationSleepCognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

The persistence of fatigue in chronic fatigue syndrome and multiple sclerosis: development of a model.

Vercoulen, J H, Swanink, C M, Galama, J M et al.·Journal of psychosomatic research·1998

This study tested whether thoughts, behaviors, and emotions affect how severe fatigue becomes and stays in ME/CFS patients. Researchers found that when patients believe their symptoms are purely physical, they tend to be less active, which makes fatigue worse. They also found that how much control patients felt they had over symptoms and how much they focused on body sensations directly affected fatigue levels. Importantly, the patterns that explained fatigue in ME/CFS were different from those in MS patients.

Cognitive Impairment
E2 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

Neuropsychology and psychology of MCS.

Fiedler, N, Kipen, H, Deluca, J et al.·Toxicology and industrial health·1994

This study looked at whether people with multiple chemical sensitivities (MCS) and chronic fatigue syndrome (CFS) have psychiatric issues or thinking problems. Researchers found that both groups reported more psychiatric diagnoses than healthy people, and both groups tended to report physical symptoms rather than emotional ones. Surprisingly, the study did not find significant cognitive impairment in MCS patients, except for a small difference in visual memory.

Cognitive Impairment
E2 ModeratePEM unclearPreliminaryCross-SectionalEditor reviewed

Chronic fatigue syndrome and a disorder resembling Sjögren's syndrome: preliminary report.

Calabrese, L H, Davis, M E, Wilke, W S·Clinical infectious diseases : an official publication of the Infectious Diseases Society of America·1994

This study looked at whether people diagnosed with ME/CFS might actually have a condition similar to Sjögren's syndrome, a disease that causes dry mouth and eyes along with immune system problems. Researchers found that many patients in their ME/CFS clinic had signs of this Sjögren's-like illness, including abnormal tests and certain antibodies in their blood. The study suggests these two conditions may overlap more often than doctors realize.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceLongitudinalEditor reviewed

Subjective and objective cognitive function in adolescent with chronic fatigue following Epstein-Barr virus infection.

Øie, Merete Glenne, Rødø, Astrid Sofie Buer, Bølgen, Maria Sletten et al.·Journal of psychosomatic research·2022

This study followed 195 teenagers who had Epstein-Barr virus infection for six months to see if they developed persistent fatigue and cognitive problems. While teenagers with ongoing fatigue reported much more trouble with thinking and memory than healthy teenagers, standard cognitive tests showed no actual differences in their thinking abilities. This suggests that cognitive difficulties in ME/CFS may feel very real to patients but are not always detectable by traditional testing methods.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Persistent neuropsychiatric impairment in HCV patients despite clearance of the virus?!

Dirks, M, Pflugrad, H, Haag, K et al.·Journal of viral hepatitis·2017

This study looked at whether people who had hepatitis C virus (HCV) infection experience long-lasting fatigue, mood problems, and memory difficulties even after the virus is cleared from their body. Researchers found that 85% of HCV patients reported chronic fatigue and about half experienced depression or anxiety, regardless of whether they still had active virus or had been treated. The findings suggest HCV may cause lasting brain-related effects that persist even after successful treatment.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceObservationalEditor reviewed

Neurocognitive and functional outcomes in persons recovering from West Nile virus illness.

Sejvar, James J, Curns, Aaron T, Welburg, Leonie et al.·Journal of neuropsychology·2008

This study looked at 54 people who had recovered from West Nile virus infection about 1.5 years after getting sick. Researchers tested their memory, thinking skills, and quality of life. They found that half of the mildly ill patients and three-quarters of those with more severe illness still had ongoing symptoms and problems with daily functioning, even though most performed normally on formal cognitive tests.

Cognitive Impairment
E2 ModeratePEM not requiredPreliminaryObservationalEditor reviewed

Behavioural effects of infectious mononucleosis.

Hall, S R, Smith, A P·Neuropsychobiology·1996

This study looked at how infectious mononucleosis (IM) affects the brain and behavior in both the short and long term. Researchers tested memory, attention, coordination, and mood in people with acute IM, people who had recovered months earlier, and healthy controls. They found that acute IM caused similar brain and behavior problems to the flu, while people recovering from IM months later showed patterns similar to those seen in chronic fatigue syndrome patients.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCase-ControlEditor reviewed

Clinical and neurocognitive features of the post Lyme syndrome.

Bujak, D I, Weinstein, A, Dornbush, R L·The Journal of rheumatology·1996

This study looked at people who had Lyme disease and continued to have fatigue, joint pain, and memory problems even after antibiotic treatment. Researchers compared 23 of these patients to 23 people who recovered fully from Lyme disease. The group with ongoing symptoms performed worse on memory and concentration tests, reported more sleep and mood problems, and showed signs of greater emotional distress.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Cognitive functioning and magnetic resonance imaging in chronic fatigue.

Cope, H, Pernet, A, Kendall, B et al.·The British journal of psychiatry : the journal of mental science·1995

This study tested whether people with chronic fatigue have real problems with thinking and memory, or whether these complaints are mainly due to depression and anxiety. Researchers gave cognitive tests and brain scans (MRI) to people with chronic fatigue, people with depression, and healthy controls. They found that people with chronic fatigue performed similarly to controls on objective tests, and brain scans showed no consistent abnormalities. The researchers concluded that complaints of cognitive problems were likely related to mood symptoms rather than physical brain changes.

Cognitive Impairment
E2 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

The impact of APOE4 on neurological symptoms after exposure to K. brevis neurotoxin.

Aldrich, Gregory J, Nkiliza, Aurore, Ferguson, Scott et al.·Environmental toxicology and pharmacology·2025

Researchers studied whether a genetic variant called APOE4 makes people more vulnerable to neurological problems from brevetoxins—toxic chemicals released by harmful algae blooms in coastal Florida waters. They found that people carrying the APOE4 gene variant reported more memory problems and fatigue during red tide events compared to those without this variant. This suggests that certain genetic factors may increase how vulnerable someone's brain is to environmental toxins.

Cognitive Impairment
E2 ModeratePEM unclearModerate confidenceCross-SectionalEditor reviewed

Bright, but allergic and neurotic? A critical investigation of the "overexcitable genius" hypothesis.

Fries, Jonathan, Baudson, Tanja Gabriele, Kovacs, Kristof et al.·Frontiers in psychology·2022

This study looked at whether highly intelligent people (members of MENSA) experience more health problems than the general population. Researchers surveyed over 600 high-IQ individuals across five European countries and found that chronic fatigue syndrome was about 5.7 times more common in this group compared to the general public. Other conditions like depression, anxiety, and autism spectrum disorders were also significantly more common, but surprisingly, allergies and autoimmune diseases were not.

Cognitive Impairment
E2 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

Self-reported cognitive impairment in individuals with Primary Immunodeficiency Disease.

Sowers, Kerri L, Gayda-Chelder, Christine A, Galantino, Mary Lou·Brain, behavior, & immunity - health·2020

This study looked at whether people with Primary Immunodeficiency Disease (PID)—a condition where the immune system doesn't work properly—experience brain fog or memory problems. Researchers asked 292 people with PID to fill out surveys about their memory, mood, and anxiety. They found that people with PID reported significantly more memory problems and higher levels of anxiety and depression compared to people without these conditions.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceObservationalEditor reviewed

A cluster analysis of serious adverse event reports after human papillomavirus (HPV) vaccination in Danish girls and young women, September 2009 to August 2017.

Ward, Daniel, Thorsen, Nicklas Myrthue, Frisch, Morten et al.·Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin·2019

This study examined adverse event reports submitted to Danish health authorities after HPV vaccination between 2009 and 2017. Researchers found that fatigue, dizziness, and headache were common symptoms reported, and noticed that some clusters of reports—particularly those mentioning cognitive problems and sleep issues—were submitted during periods of increased media coverage about vaccine safety concerns.

Autonomic Nervous SystemCognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Patients with chronic fatigue syndrome do not score higher on the autism-spectrum quotient than healthy controls: Comparison with autism spectrum disorder.

Bileviciute-Ljungar, Indre, Maroti, Daniel, Bejerot, Susanne·Scandinavian journal of psychology·2018

This study compared autistic traits in people with ME/CFS, people with autism spectrum disorder (ASD), and healthy people. Although ME/CFS and autism share some overlapping symptoms like fatigue, brain fog, and sensitivity to sound and light, the study found that people with ME/CFS did not show more autistic traits than healthy controls. People with autism did score higher on the autism assessment, showing the test can distinguish between the conditions.

Cognitive Impairment
E2 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

An assessment of fatigue in patients with postural orthostatic tachycardia syndrome.

Wise, Shelby, Ross, Amanda, Brown, Abigail et al.·Journal of health psychology·2017

This study looked at fatigue in people with POTS (postural orthostatic tachycardia syndrome), a condition that shares many symptoms with ME/CFS. Researchers asked 138 young people with POTS to describe their fatigue and brain fog using questionnaires. They found that fatigue comes in multiple forms and that people with POTS fall into two groups: those with mild symptoms and those with severe symptoms, with the severe group experiencing much worse brain fog and activity limitations.

Cognitive Impairment
E2 ModeratePEM not requiredPreliminaryLongitudinalEditor reviewed

Workers on transformation of the shelter object of the Chernobyl nuclear power plant into an ecologically-safe system show qEEG abnormalities and cognitive dysfunctions: A follow-up study.

Loganovsky, Konstantyn, Perchuk, Iryna, Marazziti, Donatella·The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry·2016

This study followed 196 workers who helped clean up and secure the damaged Chernobyl nuclear reactor between 2004 and 2008. Researchers tested their brain electrical activity and thinking skills before and after the work. The workers showed changes in brain wave patterns and developed mild memory and concentration problems after exposure to radiation, similar to symptoms seen in chronic fatigue syndrome.

Cognitive Impairment
E2 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

Endogenous event-related potentials in patients with primary Sjögren's syndrome without central nervous system involvement.

Dziadkowiak, E, Sebastian, A, Wiland, P et al.·Scandinavian journal of rheumatology·2015

This study looked at brain electrical activity in patients with Sjögren's syndrome (an autoimmune disease affecting moisture-producing glands) to see if they had subtle thinking or processing problems. Researchers found that patients showed slightly delayed brain responses to cognitive tasks, and these delays were linked to how long they'd had the disease and how inflamed their salivary glands were. Patients with both Sjögren's syndrome and chronic fatigue syndrome showed different patterns than those with Sjögren's syndrome alone.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Postural tachycardia syndrome is associated with significant symptoms and functional impairment predominantly affecting young women: a UK perspective.

McDonald, Claire, Koshi, Sharon, Busner, Lorna et al.·BMJ open·2014

This study looked at 136 people in the UK with postural tachycardia syndrome (PoTS)—a condition where your heart rate increases too much when you stand up—and found that it causes serious tiredness and functional problems, especially in young women. The researchers compared two groups of PoTS patients and found their symptoms and quality-of-life impacts were similar to those in people with chronic fatigue syndrome (ME/CFS). Importantly, there was no consistent treatment approach across patients, with some taking no medication and others on different drug combinations.

Autonomic Nervous SystemCognitive Impairment
E2 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

Confidence judgment in depression and dysphoria: the depressive realism vs. negativity hypotheses.

Szu-Ting Fu, Tiffany, Koutstaal, Wilma, Poon, Lucia et al.·Journal of behavior therapy and experimental psychiatry·2012

This study looked at how accurately people judge their own knowledge and abilities. Researchers compared three groups: healthy people, those with clinical depression, and people with chronic fatigue syndrome who felt sad or low. They found that people with depression were overly critical of themselves, while people with chronic fatigue syndrome were more realistic about their abilities—similar to healthy controls.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCase-ControlEditor reviewed

Cognitive impairment in fatigue and sleepiness associated conditions.

Neu, Daniel, Kajosch, Hendrik, Peigneux, Philippe et al.·Psychiatry research·2011

This study compared how fatigue and sleepiness affect thinking and memory. Researchers tested 15 people with ME/CFS, 15 people with sleep apnea, and 16 healthy controls using memory tests, attention tasks, and brain wave measurements. Both patient groups showed cognitive problems, though people with sleep apnea had slightly more difficulty with certain thinking tasks and movement speed.

SleepCognitive Impairment
E2 ModeratePEM not requiredPreliminaryObservationalEditor reviewed

[Omaron in the complex treatment of patients with multiple sclerosis].

Popova, N F, Kamchatnov, P R, Riabukhina, O V et al.·Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova·2010

This study tested a combination medication called omaron in 33 patients with multiple sclerosis to see if it could help with fatigue and thinking problems. After 12 weeks of treatment, patients taking omaron reported feeling less tired (28.6% improvement) and showed better memory and thinking skills compared to a similar group who didn't receive the medication. The drug was well-tolerated with no serious side effects.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Psychomotor functioning in chronic fatigue syndrome and major depressive disorder: a comparative study.

Schrijvers, D, Van Den Eede, F, Maas, Y et al.·Journal of affective disorders·2009

This study compared how quickly people with ME/CFS and depression could complete two drawing tasks—one simple and one complex. Both patient groups worked more slowly than healthy people, but the pattern of slowness differed between the two conditions. People with depression were especially slow at simple motor tasks, while both patient groups struggled similarly with the more cognitively demanding task.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceLongitudinalEditor reviewed

A 12-month follow-up study of self-management training for people with chronic disease: are changes maintained over time?

Barlow, J H, Wright, C C, Turner, A P et al.·British journal of health psychology·2005

This study followed 171 people with chronic illnesses (including ME/CFS) for 12 months after they completed a self-management training course. The improvements they experienced at 4 months—such as better fatigue management, increased confidence in managing their health, and improved mood—stayed the same at 12 months. People continued using the techniques they learned on the course.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Fatigue after breast cancer and in chronic fatigue syndrome: similarities and differences.

Servaes, Petra, Prins, Judith, Verhagen, Stans et al.·Journal of psychosomatic research·2002

This study compared 57 women with ME/CFS to 57 women who had breast cancer and were experiencing severe fatigue after treatment. Researchers measured fatigue, physical activity, mood, sleep, and concentration using questionnaires, tests, and activity monitors worn for 12 days. While both groups experienced significant fatigue, ME/CFS patients generally had more severe symptoms overall, though some breast cancer survivors reported similar problems with sleep and concentration.

SleepCognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Fatigue in disease-free cancer patients compared with fatigue in patients with chronic fatigue syndrome.

Servaes, P, van der Werf, S, Prins, J et al.·Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer·2001

This study compared fatigue in cancer survivors who had finished treatment with fatigue in people with ME/CFS. About one in five cancer survivors (19%) experienced severe fatigue similar to ME/CFS patients, even though they had been cancer-free for at least 6 months. The severely fatigued cancer survivors also reported concentration problems, reduced activity, emotional difficulties, and pain.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Neuropsychological function in patients with chronic fatigue syndrome, multiple sclerosis, and depression.

Daly, E, Komaroff, A L, Bloomingdale, K et al.·Applied neuropsychology·2001

This study compared thinking and memory skills in people with ME/CFS, multiple sclerosis, depression, and healthy controls. Researchers found that all three patient groups had trouble with memory, language, and spatial skills. Importantly, even after accounting for depression symptoms, people with ME/CFS still showed memory problems, suggesting their cognitive difficulties are not simply caused by depression.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Discriminating between chronic fatigue syndrome and depression: a cognitive analysis.

Moss-Morris, R, Petrie, K J·Psychological medicine·2001

This study compared how people with ME/CFS think and feel about their illness compared to people with depression and healthy people. The researchers found that people with ME/CFS and people with depression have different thought patterns: people with depression tend to blame themselves and doubt their worth, while people with ME/CFS focus on their physical symptoms, see themselves as sick, and tend to rest more to manage their condition. These different thinking patterns stayed consistent over 6 months and were linked to how much disability and fatigue people experienced.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceLongitudinalEditor reviewed

Natural course of symptoms in Cambodia veterans: a follow-up study.

De Vries, M, Soetekouw, P M, Van Der Meer, J W et al.·Psychological medicine·2001

Researchers followed Dutch military veterans who served in Cambodia in 1992-1993 and reported fatigue and memory problems after returning home. At 18 months later, about 39% of veterans reported feeling much better or completely recovered, while 57% still had the same symptoms and 4% felt worse. The study found that veterans who started with less severe fatigue and felt they had more control over their symptoms were more likely to improve.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

The difference in patterns of motor and cognitive function in chronic fatigue syndrome and severe depressive illness.

Lawrie, S M, MacHale, S M, Cavanagh, J T et al.·Psychological medicine·2000

This study compared thinking and physical abilities in people with ME/CFS, people with depression, and healthy individuals. Researchers found that people with ME/CFS had worse memory and thinking skills than healthy people, but generally better than those with depression. Both ME/CFS and depression groups showed significant problems with muscle strength and motor control compared to healthy controls.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

A neuropsychological study of the postpolio syndrome: support for depression without neuropsychological impairment.

Hazendonk, K M, Crowe, S F·Neuropsychiatry, neuropsychology, and behavioral neurology·2000

This study compared how well people with postpolio syndrome could think and remember compared to polio survivors without the condition and healthy controls. Although people with postpolio syndrome reported mental fatigue and memory problems, standard tests of thinking and memory showed no real differences between the groups. The researchers found that depression and worry about illness were more common in the postpolio syndrome group and may explain why patients feel cognitively impaired.

Cognitive Impairment
E2 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

Psychological states and neuropsychological performances in chronic Lyme disease.

Elkins, L E, Pollina, D A, Scheffer, S R et al.·Applied neuropsychology·1999

This study looked at mood and thinking abilities in 30 people with post-Lyme syndrome (a condition that can develop after Lyme disease). Researchers found that these patients had lower levels of positive feelings (like happiness or hopefulness) compared to the general population, but their actual thinking and memory skills tested normally. The study suggests that reduced positive mood, rather than depression or other psychiatric conditions, may be the most important psychological marker of this illness.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Post-Lyme syndrome and chronic fatigue syndrome. Neuropsychiatric similarities and differences.

Gaudino, E A, Coyle, P K, Krupp, L B·Archives of neurology·1997

This study compared people with ME/CFS and people with post-Lyme syndrome (ongoing fatigue after Lyme disease treatment) to understand how their symptoms differ. Both groups had severe fatigue and trouble thinking clearly, but people with post-Lyme syndrome showed more significant problems with memory, attention, and processing speed than people with ME/CFS. The findings suggest these two conditions may involve different types of brain function problems despite feeling similar to patients.

Cognitive Impairment
E2 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

The effects of fatigue on neuropsychological performance in patients with chronic fatigue syndrome, multiple sclerosis, and depression.

Johnson, S K, Lange, G, DeLuca, J et al.·Applied neuropsychology·1997

Researchers tested whether fatigue directly worsens brain performance on a specific attention test (PASAT) in people with ME/CFS, multiple sclerosis, and depression. They found that people with ME/CFS and depression performed worse overall on the test compared to healthy controls, but fatigue itself did not prevent people from improving with practice. This suggests that fatigue may not be the main factor directly causing the thinking difficulties some ME/CFS patients experience.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

A controlled comparison of multiple chemical sensitivities and chronic fatigue syndrome.

Fiedler, N, Kipen, H M, DeLuca, J et al.·Psychosomatic medicine·1996

This study compared people with multiple chemical sensitivities (MCS), chemical sensitivities without a clear trigger (CS), and chronic fatigue syndrome (CFS) to healthy controls. Researchers found that chemically sensitive patients reported more lifestyle disruption and avoided more substances than CFS patients, but all three patient groups had higher rates of psychiatric conditions and unexplained physical symptoms compared to healthy people. Interestingly, standard memory and thinking tests did not show significant differences between groups, suggesting that cognitive problems in these conditions may not show up on typical office-based tests.

Cognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCase-ControlEditor reviewed

Cognitive functioning and depression in patients with chronic fatigue syndrome and multiple sclerosis.

Krupp, L B, Sliwinski, M, Masur, D M et al.·Archives of neurology·1994

This study compared thinking and memory problems in people with ME/CFS, multiple sclerosis (MS), and healthy controls. People with ME/CFS showed some cognitive difficulties, particularly in processing speed and memory tasks, and had higher rates of depression. However, their cognitive problems were less widespread than those seen in MS patients, and some thinking difficulties in ME/CFS appeared linked to depression rather than the illness itself.

Cognitive Impairment
E3 PreliminaryPEM requiredPreliminaryPreprintPreprintEditor reviewed

Dissecting the genetic complexity of myalgic encephalomyelitis/chronic fatigue syndrome via deep learning-powered genome analysis.

Zhang, Sai, Jahanbani, Fereshteh, Chander, Varuna et al.·medRxiv : the preprint server for health sciences·2025

Researchers used advanced artificial intelligence to analyze the genes of ME/CFS patients and discovered 115 genes that may contribute to the disease. They found that people with ME/CFS have lower levels of these risk genes active in their immune cells and nervous system. This genetic analysis could eventually help doctors diagnose ME/CFS more accurately and identify new treatment targets.

BiomarkersImmune SystemCognitive ImpairmentPost-Exertional Malaise
E3 PreliminaryPEM unclearPreliminaryCase-ControlEditor reviewed

Improvement in Upper Limb and Systemic Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Symptoms After Surgical Treatment of Neurogenic Thoracic Outlet Syndrome.

Christoforou, Maritsa E, Lum, Ying Wei, Sroge, Sally C et al.·Cureus·2025

This case study describes a 19-year-old woman with ME/CFS who also had a condition called thoracic outlet syndrome (TOS), where nerves in the upper chest become compressed. After surgery to relieve this compression on both sides of her body, she experienced not only relief from arm numbness and tingling, but also surprising improvements in migraines, brain fog, dizziness, and vision problems. This suggests that some ME/CFS patients might benefit from being evaluated for TOS, as treating it could potentially help with multiple symptoms.

Autonomic Nervous SystemCognitive Impairment
E3 PreliminaryPEM unclearPreliminaryMechanisticEditor reviewed

Six-Week Supplementation with Creatine in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Magnetic Resonance Spectroscopy Feasibility Study at 3 Tesla.

Godlewska, Beata R, Sylvester, Amy L, Emir, Uzay E et al.·Nutrients·2024

Researchers gave 11 people with ME/CFS a creatine supplement (a natural substance that helps cells produce energy) for 6 weeks. Brain scans showed the supplement increased creatine levels in key brain regions, and participants reported feeling less fatigued, had faster reaction times on thinking tests, and showed stronger hand grip strength. The supplement was well tolerated with no side effects reported.

Cognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryMechanisticEditor reviewed

Effect of electroacupuncture on expression of protein phosphorylation in hippocampus tissues of rats with chronic fatigue syndrome.

Yang, Yan, Sun, Zhong-Ren, Li, Chao-Ran et al.·Zhen ci yan jiu = Acupuncture research·2024

Researchers tested whether acupuncture with electrical stimulation could help rats with an artificially induced fatigue-like condition. After 28 days of treatment, the acupuncture-treated rats showed improvements in their overall condition, anxiety levels, and memory compared to untreated rats. The researchers found changes in brain proteins that might explain how the treatment helped.

Cognitive Impairment
E3 PreliminaryPEM not requiredWeak / uncertainReview-NarrativeEditor reviewed

[Asthenia, mental fatigue and cognitive dysfunction].

Titova, N V, Bezdolny, Yu N, Katunina, E A·Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova·2023

This article discusses asthenia, which is a condition characterized by extreme tiredness that affects daily functioning and productivity. The authors explain that it's important to distinguish between simple chronic tiredness and chronic fatigue syndrome (CFS), and that fatigue can affect both the body and the mind. The article reviews how the brain may be involved in causing fatigue and cognitive problems, and suggests that a combination treatment using specific medications may help patients with fatigue and thinking difficulties.

Cognitive Impairment
E3 PreliminaryPEM not requiredPreliminarySystematic-ReviewEditor reviewed

Understanding mental fatigue and its detection: a comparative analysis of assessments and tools.

Kunasegaran, Kaveena, Ismail, Ahamed Miflah Hussain, Ramasamy, Shamala et al.·PeerJ·2023

Mental fatigue is a common problem that makes it harder to concentrate, process information, and make decisions. Currently, doctors mainly ask patients to describe their fatigue using questionnaires, which can be unreliable because people's answers are subjective. This review compared different methods of detecting mental fatigue—including questionnaires, heart rate measurements, stress hormones, brain scans, and eye movement tests—to find the most objective and accurate tool.

Cognitive Impairment
E3 PreliminaryPEM unclearPreliminaryObservationalEditor reviewed

Clinical effects of wasabi extract containing 6-MSITC on myalgic encephalomyelitis/chronic fatigue syndrome: an open-label trial.

Oka, Takakazu, Yamada, Yu, Lkhagvasuren, Battuvshin et al.·BioPsychoSocial medicine·2022

Researchers tested whether wasabi extract—specifically a compound called 6-MSITC that has anti-inflammatory properties—could help people with ME/CFS. Fifteen patients took the supplement daily for 12 weeks, and many reported improvements in headaches, muscle pain, brain fog, and cognitive problems like word-finding difficulties. The study found measurable improvements in pain sensitivity and thinking speed, though overall fatigue scores did not change significantly.

Pain and SensitizationCognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryReview-NarrativeEditor reviewed

[Stress, asthenia and cognitive disorders].

Vasenina, E E, Gankina, O A, Levin, O S·Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova·2022

This article examines how extreme tiredness (asthenia) relates to ME/CFS and other conditions affecting mood and thinking. The authors explain that severe fatigue can start as the body's warning signal that energy is running out, but it can develop into a serious, disabling disease on its own. They discuss how fatigue often occurs together with depression, anxiety, and problems with memory or concentration, which can make it harder for doctors to figure out what's really causing a patient's symptoms.

Cognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryReview-NarrativeEditor reviewed

Stress, Asthenia, and Cognitive Disorders.

Vasenina, E E, Gankina, O A, Levin, O S·Neuroscience and behavioral physiology·2022

This article explores the connection between extreme tiredness (asthenia), chronic fatigue syndrome (ME/CFS), and problems with thinking and mood. The authors explain that fatigue can start as your body's way of protecting itself when energy is running low, but it can develop into a serious condition that affects quality of life. They discuss how ME/CFS often appears alongside cognitive difficulties and mood changes, which can make diagnosis confusing.

Cognitive Impairment
E3 PreliminaryPEM unclearPreliminaryEditor reviewed

Living with myalgic encephalomyelitis/chronic fatigue syndrome: Experiences of occupational disruption for adults in Australia.

Bartlett, Chelsea, Hughes, Julie L, Miller, Laura·The British journal of occupational therapy·2022

This Australian study interviewed five people with ME/CFS about how the illness affected their ability to work and participate in daily activities. Participants described losing the ability to do the things that mattered to them—first hobbies and leisure activities, then work, and eventually basic self-care tasks. They also faced challenges from lack of understanding about ME/CFS, financial difficulties, and limited healthcare support.

Cognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryReview-NarrativeEditor reviewed

An attempt to explain the neurological symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Wirth, Klaus J, Scheibenbogen, Carmen, Paul, Friedemann·Journal of translational medicine·2021

This paper proposes an explanation for why ME/CFS patients experience brain fog, cognitive problems, headaches, and other neurological symptoms. The authors suggest that blood vessels in the brain may not be working properly, reducing blood flow to the brain and increasing pressure inside the skull. They argue this could also cause an overactive stress response in the nervous system, leading to the wide range of symptoms patients experience.

Cognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryObservationalEditor reviewed

Changes in the Allostatic Response to Whole-Body Cryotherapy and Static-Stretching Exercises in Chronic Fatigue Syndrome Patients vs. Healthy Individuals.

Kujawski, Sławomir, Bach, Anna M, Słomko, Joanna et al.·Journal of clinical medicine·2021

This study compared how the bodies of ME/CFS patients and healthy people respond to cold therapy combined with stretching exercises. Researchers measured fatigue, thinking ability, heart function, and nervous system activity before and after 10 sessions of treatment. They found that ME/CFS patients showed more disrupted connections between these body systems compared to healthy controls, suggesting their bodies struggle more to maintain balance under stress.

Autonomic Nervous SystemCognitive Impairment
E3 PreliminaryPEM requiredPreliminaryReview-NarrativeEditor reviewed

Understanding Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and the Emerging Osteopathic Approach: A Narrative Review.

Larrimore, Christopher, Ramnot, Amanda, Jaghab, Annmarie et al.·The Journal of the American Osteopathic Association·2019

This article reviews what scientists know about ME/CFS, including its symptoms, how it affects the body, and why it's hard to diagnose. The authors discuss both traditional medical approaches and osteopathic treatment (a type of hands-on therapy that focuses on the body's structure and function) as possible ways to help people with ME/CFS feel better. The review emphasizes that ME/CFS is a real, serious illness that deserves more awareness among doctors and better treatment options.

Immune SystemCognitive ImpairmentPost-Exertional Malaise
E3 PreliminaryPEM unclearPreliminaryCross-SectionalEditor reviewed

Brain function characteristics of chronic fatigue syndrome: A task fMRI study.

Shan, Zack Y, Finegan, Kevin, Bhuta, Sandeep et al.·NeuroImage. Clinical·2018

This study compared brain activity in ME/CFS patients and healthy people while they performed a challenging word-color matching task. ME/CFS patients were slower at the task, and their brains showed different patterns of activity—specifically, the brain signals were less complex and adaptive. The findings suggest that ME/CFS patients' brains may need to work harder or recruit more areas to handle cognitive challenges.

Cognitive Impairment
E3 PreliminaryPEM unclearPreliminaryObservationalEditor reviewed

Open-label pilot for treatment targeting gut dysbiosis in myalgic encephalomyelitis/chronic fatigue syndrome: neuropsychological symptoms and sex comparisons.

Wallis, Amy, Ball, Michelle, Butt, Henry et al.·Journal of translational medicine·2018

This study tested whether treating an overgrowth of Streptococcus bacteria in the gut could help ME/CFS patients, particularly those with brain fog and sleep problems. Forty-four patients received alternating weeks of an antibiotic and a probiotic for 4 weeks. The treatment reduced the problematic bacteria and improved several symptoms including sleep quality, attention, and memory, though it did not significantly affect fatigue or mood.

SleepCognitive Impairment
E3 PreliminaryPEM unclearPreliminaryCross-SectionalEditor reviewed

Task Related Cerebral Blood Flow Changes of Patients with Chronic Fatigue Syndrome: An Arterial Spin Labeling Study.

Staud, Roland, Boissoneault, Jeff, Craggs, Jason G et al.·Fatigue : biomedicine, health & behavior·2018

Researchers used advanced brain imaging to track blood flow while patients with ME/CFS and healthy people performed a challenging mental task. They found that while the overall amount of blood flowing to the brain was similar in both groups, specific brain regions showed different patterns when people were recovering from fatigue. In ME/CFS patients, fatigue improved when blood flow decreased in certain memory and attention areas, whereas in healthy people, fatigue improved when blood flow increased in those same areas.

Cognitive Impairment
E3 PreliminaryPEM not requiredModerate confidenceMethods-PaperEditor reviewed

Psychometric Properties and Factor Structure of a Long and Shortened Version of the Cognitive and Behavioural Responses Questionnaire.

Ryan, Elizabeth G, Vitoratou, Silia, Goldsmith, Kimberley A et al.·Psychosomatic medicine·2018

This study tested a questionnaire designed to measure how people with ME/CFS think and behave in response to their illness—such as pushing through fatigue or avoiding activity. Researchers created a shorter, easier-to-use version of the original questionnaire by removing unnecessary questions while keeping the important ones. Both versions were found to be reliable and accurate tools for understanding these psychological responses.

Cognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryCross-SectionalEditor reviewed

Emotional conflict processing in adolescent chronic fatigue syndrome: A pilot study using functional magnetic resonance imaging.

Wortinger, Laura Anne, Endestad, Tor, Melinder, Annika Maria D et al.·Journal of clinical and experimental neuropsychology·2017

This study looked at how the brains of teenagers with ME/CFS process emotions and handle conflicting information. Researchers used brain imaging to watch what happened when young people with ME/CFS and healthy teenagers tried to identify emotions in faces while being distracted by conflicting words. Teenagers with ME/CFS showed weaker brain responses in areas that handle emotions and decision-making, and their brain activity was linked to how severe their fatigue was.

Cognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryLongitudinalEditor reviewed

Neurocognitive improvements after best-practice intervention for chronic fatigue syndrome: Preliminary evidence of divergence between objective indices and subjective perceptions.

Cvejic, Erin, Lloyd, Andrew R, Vollmer-Conna, Uté·Comprehensive psychiatry·2016

This study tested whether a 12-week program combining graded activity and cognitive training could help ME/CFS patients with thinking and memory problems. Researchers measured improvements in two ways: by asking patients how they felt, and by giving them objective tests of mental performance. They found that patients showed real, measurable improvements in processing speed and accuracy on cognitive tests, and their stress response (measured by heart rate patterns) also improved.

Cognitive Impairment
E3 PreliminaryPEM unclearPreliminaryCross-SectionalEditor reviewed

Intrinsic Functional Hypoconnectivity in Core Neurocognitive Networks Suggests Central Nervous System Pathology in Patients with Myalgic Encephalomyelitis: A Pilot Study.

Zinn, Marcie L, Zinn, Mark A, Jason, Leonard A·Applied psychophysiology and biofeedback·2016

Researchers used EEG brain scans to measure electrical activity and communication between brain regions in 9 ME/CFS patients and 9 healthy controls. They found that people with ME/CFS had weaker electrical activity in the back of the brain and reduced communication between three important brain networks that help with thinking, attention, and rest. These differences suggest that ME/CFS involves measurable changes in how the brain works.

Cognitive Impairment
E3 PreliminaryPEM unclearModerate confidenceMethods-PaperEditor reviewed

Maximizing potential impact of experimental research into cognitive processes in health psychology: A systematic approach to material development.

Hughes, Alicia M, Gordon, Rola, Chalder, Trudie et al.·British journal of health psychology·2016

This paper is a guide for researchers on how to properly design experiments that test whether people with conditions like ME/CFS have unconscious biases in how they pay attention to and interpret information about their illness. The authors explain that many past studies used different, untested materials, making it hard to compare results. They provide a step-by-step process and practical tools to help researchers create better, standardized materials for these types of studies.

Cognitive Impairment
E3 PreliminaryPEM requiredModerate confidenceMethods-PaperEditor reviewed

Accurate diagnosis of myalgic encephalomyelitis and chronic fatigue syndrome based upon objective test methods for characteristic symptoms.

Twisk, Frank Nm·World journal of methodology·2015

ME and CFS are often treated as the same condition, but they are actually different illnesses with some overlapping symptoms. ME has specific features like muscle weakness, brain fog, heart and circulation problems, and especially a distinctive symptom called post-exertional malaise—where patients feel much worse after even small amounts of activity. Because many ME/CFS symptoms feel subjective, some doctors have questioned whether they are real physical problems, but this article argues that objective medical tests can measure key symptoms and help doctors diagnose these conditions more accurately.

Cognitive ImpairmentPost-Exertional Malaise
E3 PreliminaryPEM not requiredPreliminaryCross-SectionalEditor reviewed

Less efficient and costly processes of frontal cortex in childhood chronic fatigue syndrome.

Mizuno, Kei, Tanaka, Masaaki, Tanabe, Hiroki C et al.·NeuroImage. Clinical·2015

This study looked at how children with ME/CFS use their brains when doing challenging thinking tasks. When performing two tasks at once (like sorting letters while reading a story), children with ME/CFS had to activate much larger areas of their brains compared to healthy children. This suggests their brains work harder and less efficiently to accomplish the same tasks, which may contribute to the exhaustion they experience.

Cognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryObservationalEditor reviewed

A prospective, proof-of-concept investigation of KPAX002 in chronic fatigue syndrome.

Kaiser, Jon D·International journal of clinical and experimental medicine·2015

This small study tested a combination treatment called KPAX002, which pairs a stimulant medication (methylphenidate) with nutrients thought to support energy production in cells. Fifteen people with ME/CFS took this combination for 12 weeks, and researchers measured changes in fatigue and concentration problems using standard questionnaires. Most participants (87%) showed meaningful improvement in fatigue, and the treatment was generally safe and well tolerated.

Cognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryMechanisticEditor reviewed

Phenylephrine alteration of cerebral blood flow during orthostasis: effect on n-back performance in chronic fatigue syndrome.

Medow, Marvin S, Sood, Shilpa, Messer, Zachary et al.·Journal of applied physiology (Bethesda, Md. : 1985)·2014

Many ME/CFS patients experience dizziness and cognitive problems when standing up because blood flow to the brain decreases. This study tested whether a medication called phenylephrine, which raises blood pressure, could help restore brain blood flow and improve thinking tasks during standing. The researchers found that phenylephrine reduced the brain blood flow drop and helped ME/CFS patients perform better on memory tests while upright.

Autonomic Nervous SystemCognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryReview-NarrativeEditor reviewed

Neurocognitive impairment in childhood chronic fatigue syndrome.

Mizuno, Kei, Watanabe, Yasuyoshi·Frontiers in physiology·2013

This study examined how ME/CFS affects thinking and attention skills in children and teenagers. Researchers found that young people with ME/CFS have difficulty with tasks that require switching between activities or paying attention to multiple things at once. The brain regions responsible for these skills are still developing during childhood, and severe fatigue may slow down or disrupt this normal development.

Cognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryReview-NarrativeEditor reviewed

Caught in the thickness of brain fog: exploring the cognitive symptoms of Chronic Fatigue Syndrome.

Ocon, Anthony J·Frontiers in physiology·2013

ME/CFS causes cognitive difficulties that patients often describe as "brain fog"—a feeling of foggy thinking, slow mental processing, and trouble concentrating. This review suggests brain fog may result from reduced blood flow to the brain combined with the physical stress of standing (which worsens symptoms in many patients), plus the extra mental effort required to complete tasks. Understanding these overlapping factors could help explain why cognitive symptoms feel so exhausting.

Autonomic Nervous SystemCognitive Impairment
E3 PreliminaryPEM unclearPreliminaryReview-NarrativeEditor reviewed

Brain dysfunction as one cause of CFS symptoms including difficulty with attention and concentration.

Natelson, Benjamin H·Frontiers in physiology·2013

This study suggests that ME/CFS is not one single disease but rather multiple conditions with different underlying causes. By grouping patients based on specific characteristics—like whether they have psychiatric diagnoses, fibromyalgia, or blood pressure problems when standing—researchers found that different groups showed different types of brain dysfunction. This approach could help explain why some patients experience trouble with concentration and attention in different ways.

Autonomic Nervous SystemCognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryMechanisticEditor reviewed

[Effect of acupuncture intervention on learning-memory ability and cerebral superoxide dismutase activity and malonaldehyde concentration in chronic fatigue syndrome rats].

Liu, Chang-zheng, Lei, Bo·Zhen ci yan jiu = Acupuncture research·2013

Researchers tested whether acupuncture could help rats with chronic fatigue syndrome (CFS) learn and remember better. They found that acupuncture improved memory performance in fatigued rats and also increased protective molecules in the brain while reducing harmful ones, suggesting acupuncture may work by protecting brain cells from oxidative damage.

Cognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryCross-SectionalEditor reviewed

Metacognitive factors in chronic fatigue syndrome.

Maher-Edwards, Lorraine, Fernie, Bruce A, Murphy, Gabrielle et al.·Clinical psychology & psychotherapy·2012

This study explored how ME/CFS patients think about their thinking—specifically, their beliefs about analyzing and solving problems related to their symptoms. Researchers found that patients have both helpful and unhelpful thoughts about trying to understand their illness, and they often focus on either distracting themselves or monitoring their symptoms closely. The study suggests that these thought patterns may play a role in how ME/CFS symptoms develop or persist.

Cognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryCross-SectionalEditor reviewed

Postural neurocognitive and neuronal activated cerebral blood flow deficits in young chronic fatigue syndrome patients with postural tachycardia syndrome.

Stewart, Julian M, Medow, Marvin S, Messer, Zachary R et al.·American journal of physiology. Heart and circulatory physiology·2012

When people with ME/CFS try to stand upright or tilt backward, their brain doesn't get enough blood flow to think clearly, and their thinking problems get worse as their body position changes. In healthy people, brain blood flow increases during hard thinking tasks, but in ME/CFS patients, this normal response is broken—their brains don't increase blood flow when doing difficult mental tasks.

Autonomic Nervous SystemCognitive Impairment
E3 PreliminaryPEM not requiredModerate confidenceObservationalEditor reviewed

Increasing orthostatic stress impairs neurocognitive functioning in chronic fatigue syndrome with postural tachycardia syndrome.

Ocon, Anthony J, Messer, Zachary R, Medow, Marvin S et al.·Clinical science (London, England : 1979)·2012

This study tested whether standing at increasing angles on a tilt table—a procedure that stresses the body's ability to maintain blood flow while upright—makes 'brain fog' worse in people with ME/CFS who also have POTS (a condition causing rapid heartbeat when standing). Researchers found that when people with CFS/POTS stood at steeper angles while doing concentration and memory tests, their performance got worse compared to healthy people, suggesting that orthostatic stress (the challenge of staying upright) does interfere with thinking and memory.

Autonomic Nervous SystemCognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryMechanisticEditor reviewed

[Effect of electroacupuncture at Shenshu (BL 23) and Zusanli (ST 36) on the event-related potentials of chronic fatigue syndrome].

Cheng, Ci-Song, Zhu, Yi-Hui, Liang, Fan-Rong et al.·Zhongguo zhen jiu = Chinese acupuncture & moxibustion·2010

This study looked at whether acupuncture can help ME/CFS patients by examining brain wave patterns that reflect attention and thinking. Researchers compared brain signals in healthy people and ME/CFS patients at different times of day, then treated some ME/CFS patients with acupuncture. They found that acupuncture helped restore normal daily rhythms in brain activity and improved daytime thinking ability.

Cognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryCross-SectionalEditor reviewed

Memory and attention problems in children with chronic fatigue syndrome or myalgic encephalopathy.

Haig-Ferguson, A, Tucker, P, Eaton, N et al.·Archives of disease in childhood·2009

This study looked at 20 children with ME/CFS who had memory and attention problems. Researchers asked the children, their parents, and teachers about these difficulties, and then gave the children a series of tests to measure how well they could focus, remember things, and process information. The children's test scores showed they had real difficulties with attention and memory compared to healthy children their age.

Cognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryReview-NarrativeEditor reviewed

Diagnostic and treatment challenges of chronic fatigue syndrome: role of immediate-release methylphenidate.

Valdizán Usón, José Ramón, Idiazábal Alecha, María Angeles·Expert review of neurotherapeutics·2008

This study explores whether a medication called methylphenidate (commonly known as Ritalin) might help people with ME/CFS who experience brain fog, memory problems, and difficulty concentrating. The authors reviewed existing research, including one small study showing positive results, and discussed how this medication works in the brain to boost focus and thinking speed. They suggest methylphenidate could be a promising treatment option worth further investigation for ME/CFS patients.

Cognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryReview-NarrativeEditor reviewed

[School phobia and childhood chronic fatigue syndrome (CCFS)].

Tomoda, Akemi·Nihon rinsho. Japanese journal of clinical medicine·2007

This review examines childhood chronic fatigue syndrome (CCFS), a serious condition where children experience extreme tiredness that cannot be explained by other medical or mental health problems. Children with CCFS often struggle with memory and concentration, sleep problems, and symptoms related to their nervous system. The authors suggest that CCFS may involve changes in how the brain functions, which could explain why patients experience fatigue, thinking difficulties, and memory problems.

Autonomic Nervous SystemCognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryRCTEditor reviewed

Effects of elevated plasma tryptophan on brain activation associated with the Stroop task.

Morgan, Rhian M, Parry, Allyson M M, Arida, Ricardo M et al.·Psychopharmacology·2007

This study looked at how a dietary supplement called tryptophan affects the brain's activity during mental tasks in people experiencing central fatigue (like in ME/CFS). Researchers used brain imaging to watch what happens when people take tryptophan versus a placebo while doing a challenging attention test. They found that tryptophan slowed down responses and changed brain activity patterns in several regions, particularly in areas related to awareness and processing information.

Cognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryCross-SectionalEditor reviewed

Functional neuroimaging correlates of mental fatigue induced by cognition among chronic fatigue syndrome patients and controls.

Cook, Dane B, O'Connor, Patrick J, Lange, Gudrun et al.·NeuroImage·2007

This study used brain imaging to see how the brains of ME/CFS patients and healthy people respond during mentally tiring tasks. Researchers found that feelings of mental fatigue were linked to activity in specific brain regions during a difficult memory task, and that ME/CFS patients showed greater brain activity in these areas compared to healthy controls, even though they were doing the same task.

Cognitive Impairment
E3 PreliminaryPEM not requiredModerate confidenceReview-NarrativeEditor reviewed

[Clinical features of chronic fatigue syndrome--symptoms].

Ban, Nobutaro, Saiki, Takuya, Ko, Gyoshin et al.·Nihon rinsho. Japanese journal of clinical medicine·2007

This review article summarizes the most common symptoms experienced by people with ME/CFS. The researchers identified and described the top 10 symptoms in detail, including severe fatigue, problems with memory and concentration, muscle pain, poor sleep, and headaches. Understanding these symptom patterns can help doctors recognize and diagnose ME/CFS more accurately.

Pain and SensitizationCognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryCross-SectionalEditor reviewed

Reduced responsiveness is an essential feature of chronic fatigue syndrome: a fMRI study.

Tanaka, Masaaki, Sadato, Norihiro, Okada, Tomohisa et al.·BMC neurology·2006

Researchers used brain imaging to compare how the brains of ME/CFS patients and healthy people responded to sounds while doing a tiring visual task. They found that healthy people's brains stayed responsive to sounds during the task, but ME/CFS patients' brains showed reduced responses to sounds—and this reduction matched how fatigued the patients felt. This suggests that ME/CFS may involve the brain becoming less able to process information that isn't directly related to the main task at hand.

Cognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryMethods-PaperEditor reviewed

Exploration of statistical dependence between illness parameters using the entropy correlation coefficient.

Craddock, R Cameron, Taylor, Renee, Broderick, Gordon et al.·Pharmacogenomics·2006

Researchers tested a new statistical method called the entropy correlation coefficient to identify which ME/CFS symptoms and test results are related to each other. They studied 130 women and found that fatigue-related measures were strongly connected to each other, as were general quality-of-life measures and depression scores. Importantly, they discovered some relationships between cognitive test results and ME/CFS that hadn't been found with traditional statistical methods.

Cognitive Impairment
E3 PreliminaryPEM unclearPreliminaryCase-ControlEditor reviewed

Efficacy of neurotropin in chronic fatigue syndrome: a case report.

Toda, Katsuhiro, Kimura, Hiroaki·Hiroshima journal of medical sciences·2006

This case report describes one 28-year-old man with ME/CFS who was treated with a medication called Neurotropin (four tablets daily). His fatigue and widespread pain began improving within a week, and his sleep, focus, and memory improved within two weeks. He stopped taking the medication after 11 weeks and remained symptom-free for at least 5 months afterward.

Pain and SensitizationSleepCognitive Impairment
E3 PreliminaryPEM not requiredModerate confidenceCross-SectionalEditor reviewed

Objective evidence of cognitive complaints in Chronic Fatigue Syndrome: a BOLD fMRI study of verbal working memory.

Lange, G, Steffener, J, Cook, D B et al.·NeuroImage·2005

This study used brain imaging to see what happens when people with ME/CFS listen to complex spoken information. Researchers found that people with ME/CFS could understand the information just as well as healthy people, but their brains had to work much harder to do it—using more brain regions and requiring greater effort. This provides scientific proof that the thinking and concentration difficulties ME/CFS patients report are real and visible on brain scans.

Cognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryObservationalEditor reviewed

Learning and memorization impairment in childhood chronic fatigue syndrome manifesting as school phobia in Japan.

Miike, Teruhisa, Tomoda, Akemi, Jhodoi, Takako et al.·Brain & development·2004

This study followed children with chronic fatigue syndrome (CFS) in Japan over 15 years to understand why they experience severe tiredness and difficulty learning and remembering information. The researchers found that these children had problems with their autonomic nervous system (the automatic system controlling heart rate, temperature, and digestion), disrupted sleep-wake cycles similar to jet lag, and reduced blood flow to certain brain areas. Understanding these patterns may help explain why learning becomes so difficult for children with CFS.

SleepCognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryReview-NarrativeEditor reviewed

Subjective health complaints, sensitization, and sustained cognitive activation (stress).

Eriksen, H R, Ursin, H·Journal of psychosomatic research·2004

This review suggests that common symptoms like pain, tiredness, sleep problems, and digestive issues in conditions like ME/CFS may occur when the body's normal sensing system becomes overly sensitive. Rather than being caused by hidden disease, these symptoms may develop when people experience sustained stress and feel helpless, causing the nervous system to amplify normal bodily signals until they become unbearable.

Pain and SensitizationCognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryCross-SectionalEditor reviewed

Single-photon emission computerized tomography and neurocognitive function in patients with chronic fatigue syndrome.

Schmaling, Karen B, Lewis, David H, Fiedelak, Jessica I et al.·Psychosomatic medicine·2003

Researchers used brain imaging scans to compare how the brains of people with ME/CFS and healthy people work during a challenging listening and memory task. People with ME/CFS performed just as well on the task as healthy people, but reported feeling like they had to work much harder mentally. The brain scans showed that people with ME/CFS had a different pattern of brain activity—more spread out rather than focused in specific areas—suggesting their brains may be working less efficiently.

Cognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryCase-ControlEditor reviewed

Treatment of chronic fatigue with neurofeedback and self-hypnosis.

Hammond, D C·NeuroRehabilitation·2001

This study describes one young woman with ME/CFS whose main problem was brain fog and difficulty thinking clearly. Doctors found an abnormal brain wave pattern on her EEG scan and treated her with two techniques: neurofeedback (training to change brain wave patterns) and self-hypnosis. She felt significantly better, with improvements in fatigue and mental clarity that lasted for at least 9 months.

Cognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryCross-SectionalEditor reviewed

Cortical motor potential alterations in chronic fatigue syndrome.

Gordon, R, Michalewski, H J, Nguyen, T et al.·International journal of molecular medicine·1999

Researchers measured electrical brain activity in people with ME/CFS while they performed tasks like responding to targets, remembering information, and moving on command. They found that people with ME/CFS were slower at these tasks and showed weaker brain signals before moving, suggesting their brains may prepare for movement differently. However, their brains processed sensory information and made decisions normally.

Cognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryCase-ControlEditor reviewed

EEG biofeedback as a treatment for chronic fatigue syndrome: a controlled case report.

James, L C, Folen, R A·Behavioral medicine (Washington, D.C.)·1996

This study tested whether a brain training technique called EEG neurofeedback could help a person with chronic fatigue syndrome (CFS). The patient received this treatment and was tested before and after using standard cognitive (thinking) tests. The results showed improvements in memory, thinking skills, daily functioning, and overall quality of life.

Cognitive Impairment
E3 PreliminaryPEM not requiredModerate confidenceReview-NarrativeEditor reviewed

Research on cognitive complaints and cognitive functioning in patients with chronic fatigue syndrome (CFS): What conclusions can we draw?

Wearden, A J, Appleby, L·Journal of psychosomatic research·1996

People with ME/CFS often report problems with memory and concentration, but when researchers test their cognitive abilities in the lab, they don't find major deficits. This review suggests the gap between what patients experience and what tests show might be because lab tests don't measure 'real-world' thinking very well. In ME/CFS, everyday mental tasks may be using up so much energy that patients have less mental flexibility left over for other things.

Cognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryReview-NarrativeEditor reviewed

Neuropsychiatric status of patients with chronic fatigue syndrome: an overview.

Deluca, J, Johnson, S K, Natelson, B H·Toxicology and industrial health·1994

This review examines how ME/CFS affects thinking, memory, and mental health. Researchers compared people with ME/CFS to people with multiple sclerosis, depression, and healthy individuals to understand the neuropsychiatric symptoms (brain and mental health effects) that often accompany the chronic fatigue. The study suggests that cognitive problems in ME/CFS are a real biological feature of the illness, not simply depression.

Cognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryReview-NarrativeEditor reviewed

Cognitive functioning of patients with chronic fatigue syndrome.

Johnson, S K, DeLuca, J, Fiedler, N et al.·Clinical infectious diseases : an official publication of the Infectious Diseases Society of America·1994

Many people with ME/CFS experience brain fog and difficulty thinking clearly, which can be just as disabling as physical symptoms. This review examined research on these cognitive problems and found that the issue may not be with memory itself, but rather with how the brain processes information—like a computer that struggles to handle incoming data quickly enough. Understanding this difference is important for developing better treatments and support strategies.

Cognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryCross-SectionalEditor reviewed

Analysis of neuropsychological functioning in patients with chronic fatigue syndrome.

Grafman, J, Schwartz, V, Dale, J K et al.·Journal of neurology, neurosurgery, and psychiatry·1993

This study tested memory and thinking skills in 20 people with ME/CFS who reported memory problems. The researchers found that patients did have mild difficulty with memory tasks that required deep thinking and organization of information, but performed normally on other types of memory tests. Importantly, the severity of fatigue and other physical findings did not predict how well people performed on memory tests.

Cognitive Impairment
E3 PreliminaryPEM unclearPreliminaryObservationalEditor reviewed

Sensory and cognitive event-related potentials in myalgic encephalomyelitis.

Prasher, D, Smith, A, Findley, L·Journal of neurology, neurosurgery, and psychiatry·1990

This study tested whether ME/CFS patients have objective brain activity differences related to thinking and attention. Researchers used special sensors to measure how the brain responds to sounds and tasks requiring concentration. While basic sensory responses were normal, they found that brain signals related to attention and processing speed were slower in about one-third to one-half of patients tested, suggesting ME/CFS affects how the brain handles information rather than basic sensation.

Cognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryReview-NarrativeEditor reviewed

Chronic fatigue syndrome and the psychiatrist.

Abbey, S E, Garfinkel, P E·Canadian journal of psychiatry. Revue canadienne de psychiatrie·1990

This review article examines ME/CFS and the role psychiatrists can play in caring for patients. The authors note that ME/CFS involves thinking difficulties, mood changes, and behavioral symptoms alongside fatigue. They explain what psychiatrists should know about the condition and how they can help in assessment and treatment.

Cognitive Impairment
E3 PreliminaryPEM unclearModerate confidenceGuidelineEditor reviewed

Improving quality in adult long covid services: Findings from the LOCOMOTION quality improvement collaborative.

Darbyshire, Julie, Greenhalgh, Trisha, Bakerly, Nawar D et al.·Clinical medicine (London, England)·2024

This study looked at how ten long COVID clinics across the UK could improve their care for patients by sharing what they were learning with each other. From 2021 to 2023, clinic staff and patients met regularly to discuss the best ways to help people with long COVID, focusing on problems like breathing difficulties, heart rate issues, tiredness, and brain fog. The team created practical guides to help doctors provide better, more consistent care.

Autonomic Nervous SystemCognitive Impairment
E3 PreliminaryPEM unclearModerate confidenceGuidelineEditor reviewed

Forming a consensus opinion to inform long COVID support mechanisms and interventions: a modified Delphi approach.

Owen, Rebecca, Ashton, Ruth E M, Ferraro, Francesco V et al.·EClinicalMedicine·2023

Researchers gathered opinions from doctors, physiotherapists, patients with Long COVID, and scientists across multiple countries to agree on the best ways to support and treat Long COVID. Using three rounds of surveys, they found strong agreement that Long COVID needs specialized, personalized care plans that address individual symptoms like fatigue, brain fog, and breathing problems, with emphasis on pacing and gradually returning to daily activities.

Cognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryReview-NarrativeEditor reviewed

Post-COVID-19 syndrome: epidemiology, diagnostic criteria and pathogenic mechanisms involved.

Carod-Artal, F J·Revista de neurologia·2021

Many people who have had COVID-19, even mild cases, don't fully recover and experience long-lasting symptoms for months afterward. This article reviews what we know about post-COVID-19 syndrome, including who gets it, what symptoms they have, and what might be causing it. Common symptoms include fatigue, breathing problems, difficulty concentrating, anxiety, and depression. The exact biological reasons why this happens are still unknown, though experts think abnormal immune and inflammatory responses may play a role.

DiagnosticsCognitive Impairment
E3 PreliminaryPEM unclearPreliminaryCross-SectionalEditor reviewed

Reduced Adenosine Triphosphate-to-Phosphocreatine Ratios in Neuropsychiatric Post-COVID Condition: Evidence From 31P Magnetic Resonance Spectroscopy.

Weber-Fahr, Wolfgang, Dommke, Sandra, Sack, Markus et al.·Biological psychiatry·2026

This study looked at how the brain produces and uses energy in people with long COVID and cognitive problems. Using a special brain imaging scan, researchers found that people with long COVID have lower energy levels in a part of their brain called the cingulate cortex, and this energy shortage is linked to thinking and memory problems. The findings suggest that problems with how brain cells produce energy may be a key reason why some people experience cognitive difficulties after COVID-19.

Cognitive Impairment
E3 PreliminaryPEM unclearPreliminaryCross-SectionalEditor reviewed

Autonomic phenotyping, brain blood flow control, and cognitive-motor-integration in Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome: A pilot study.

Badhwar, Smriti, Pereira, Tania J, Kerr, Kathleen et al.·Autonomic neuroscience : basic & clinical·2025

This study compared how the nervous systems of ME/CFS patients, Long COVID patients, and healthy people respond to physical stress tests like breathing different air mixtures and tilting upright. The researchers found that ME/CFS and Long COVID patients had different patterns of problems: ME/CFS patients showed difficulty controlling blood flow to the brain during one test, which was linked to coordination problems, while Long COVID patients had lower oxygen levels when upright and their nervous systems didn't adapt as well.

Autonomic Nervous SystemCognitive Impairment
E3 PreliminaryPEM not requiredWeak / uncertainReview-NarrativeEditor reviewed

Retracted: Chronic Epipharyngitis Treated with Epipharyngeal Abrasion Therapy: Symptoms, Diagnosis, Pathogenesis, and Treatment Outcomes.

Harabuchi, Yasuaki, Kumai, Takumi, Nishi, Kensuke et al.·JMA journal·2025

This article discusses chronic epipharyngitis—long-term inflammation in the upper throat—and describes a treatment called epipharyngeal abrasion therapy (EAT) that aims to reduce this inflammation. The authors note that this throat inflammation may cause various symptoms including fatigue, brain fog, dizziness, and cough, and they review evidence that EAT might help some patients, including those with long COVID. However, this paper has been retracted and should not be relied upon for clinical decisions.

Cognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryReview-NarrativeEditor reviewed

The interplay between Sars-Cov-2 infection related cardiovascular diseases and depression. Common mechanisms, shared symptoms.

Gonjilashvili, Ana, Tatishvili, Sophio·American heart journal plus : cardiology research and practice·2024

This review examines how COVID-19 can affect both the heart and mental health, and why these problems often occur together. The authors explain that inflammation, unhealthy lifestyle changes, and communication between organs may all play a role. They note that long COVID shares many symptoms with heart and brain problems—like fatigue, brain fog, dizziness, chest pain, and depression—which is why patients need care from multiple medical specialists.

Autonomic Nervous SystemCognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryEditor reviewed

The Potential Role of Hypothalamic Phospholipid Liposomes in the Supportive Therapy of Some Manifestations of Post-COVID-19 Condition: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Brain Fog.

Menichetti, Francesco·Journal of clinical medicine·2023

This article discusses how a treatment called hypothalamic phospholipid liposomes might help with ME/CFS and brain fog symptoms in people with Long COVID. These liposomes are small fatty particles that are already available as a supportive treatment for brain and hormone-related problems. The authors suggest this treatment could be helpful based on how it works and their early clinical experiences, though more rigorous testing is still needed.

Cognitive Impairment
E3 PreliminaryPEM unclearPreliminaryCross-SectionalEditor reviewed

Altered brain connectivity in Long Covid during cognitive exertion: a pilot study.

Barnden, Leighton, Thapaliya, Kiran, Eaton-Fitch, Natalie et al.·Frontiers in neuroscience·2023

Researchers used advanced brain imaging to compare how the brains of Long Covid patients and healthy people respond during a challenging thinking task. They found that Long Covid patients showed different patterns of communication between brain regions, particularly in areas that control alertness, heart rate, and sleep. These brain connection differences were linked to how disabled patients felt and their autonomic nervous system symptoms.

Cognitive Impairment
E3 PreliminaryPEM not requiredModerate confidenceMethods-PaperEditor reviewed

The Cognitive and Behavioural Responses to Symptoms Questionnaire (CBRQ): Development, reliability and validity across several long-term conditions.

Picariello, Federica, Chilcot, Joseph, Chalder, Trudie et al.·British journal of health psychology·2023

This study tested a questionnaire called the CBRQ that measures how people think about and respond to their symptoms in ways that might make them worse or keep them the same. The researchers checked whether this questionnaire works well across different long-term illnesses, including chronic fatigue syndrome (ME/CFS), and found that it reliably measures seven different thought and behaviour patterns. They also created and tested a shorter version of the questionnaire that works just as well.

Cognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryCross-SectionalEditor reviewed

What is brain fog?

McWhirter, Laura, Smyth, Heather, Hoeritzauer, Ingrid et al.·Journal of neurology, neurosurgery, and psychiatry·2023

This study looked at how people describe 'brain fog' by analyzing online discussions on Reddit. Researchers found that brain fog involves many different experiences—trouble remembering things, difficulty concentrating, feeling disconnected from reality, thinking slowly, trouble communicating, and fatigue. Brain fog appeared in discussions about many conditions, with long COVID being the most commonly mentioned cause.

Cognitive Impairment
E3 PreliminaryPEM requiredPreliminaryReview-NarrativeEditor reviewed

Review of the Midbrain Ascending Arousal Network Nuclei and Implications for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), Gulf War Illness (GWI) and Postexertional Malaise (PEM).

Baraniuk, James N·Brain sciences·2022

This review examines a brain region called the midbrain and how it might contribute to post-exertional malaise (PEM)—the worsening of symptoms after activity that happens in ME/CFS. When ME/CFS patients did exercise in a study, their midbrain showed increased activity during mental tasks, while Gulf War Illness patients showed the opposite pattern. The authors suggest that problems in this brain region could explain why ME/CFS patients have trouble with energy, sleep, mood, pain, and temperature control, especially after exertion.

Cognitive ImpairmentPost-Exertional Malaise
E3 PreliminaryPEM unclearPreliminaryReview-NarrativeEditor reviewed

Possible Application of Melatonin in Long COVID.

Cardinali, Daniel P, Brown, Gregory M, Pandi-Perumal, Seithikurippu R·Biomolecules·2022

This review examines whether melatonin, a natural hormone that regulates sleep, might help people with long COVID who experience symptoms similar to ME/CFS—such as brain fog, fatigue, and muscle pain. Melatonin has several properties that could potentially help: it reduces inflammation, fights harmful molecules in the body, supports immune function, and protects nerve cells. The authors suggest melatonin might be worth studying further as a treatment for the lingering cognitive and pain symptoms some long COVID patients experience.

Pain and SensitizationSleepCognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryCase-ControlEditor reviewed

Assessment of Hearing and Vestibular Functions in a Post-COVID-19 Patient: A Clinical Case Study.

Andreeva, Irina Germanovna, Gvozdeva, Alisa, Pimenova, Vera et al.·Diagnostics (Basel, Switzerland)·2022

This study examined one patient who had both long COVID and chronic fatigue syndrome. Doctors tested their hearing and balance systems, and found problems with how the brain processes sounds—particularly difficulty with rapid sound changes and understanding speech. Interestingly, the nerve fibers in the skin and eyes were normal, suggesting the problem is in how the brain handles auditory information rather than in damaged nerves. The researchers suggest that this auditory processing difficulty may add extra strain to the nervous system and worsen fatigue during daily activities.

Cognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryEditor reviewed

An Unexpected Journey: The Lived Experiences of Patients with Long-Term Cognitive Sequelae After Recovering from COVID-19.

Loft, Mia I, Foged, Eva M, Koreska, Mai·Qualitative health research·2022

This study listened to people who experienced long-lasting thinking and memory problems after recovering from COVID-19. Patients described how these cognitive symptoms disrupted their daily lives, work, and relationships, and left them feeling anxious and uncertain about their future. The researchers suggest that doctors and researchers could learn from how people with similar conditions—like ME/CFS—manage their symptoms while waiting for treatments.

Cognitive Impairment
E3 PreliminaryPEM not requiredModerate confidenceReview-NarrativeEditor reviewed

Central sensitivity and fibromyalgia.

Mezhov, Veronica, Guymer, Emma, Littlejohn, Geoffrey·Internal medicine journal·2021

Fibromyalgia and ME/CFS are conditions where the nervous system becomes oversensitive, causing widespread pain, fatigue, sleep problems, and brain fog. These conditions often occur together and share similar underlying problems with how the brain and spinal cord process pain and other signals. This review explains what causes these conditions and how doctors can recognize and treat them using a combination of education, exercise, stress management, and medications.

SleepCognitive Impairment
E3 PreliminaryPEM unclearPreliminaryObservationalEditor reviewed

An Open-Label, Pilot Trial of HRG80™ Red Ginseng in Chronic Fatigue Syndrome, Fibromyalgia, and Post-Viral Fatigue.

Teitelbaum, Jacob, Goudie, Sarah·Pharmaceuticals (Basel, Switzerland)·2021

This study tested a special form of red ginseng called HRG80 in people with ME/CFS, fibromyalgia, and post-COVID fatigue. Over one month, 188 patients took daily ginseng supplements and reported their symptoms. About 60% of participants felt better, with improvements in energy, mental clarity, sleep, and stamina.

Pain and SensitizationSleepCognitive Impairment
E3 PreliminaryPEM unclearPreliminaryReview-NarrativeEditor reviewed

The link between idiopathic intracranial hypertension, fibromyalgia, and chronic fatigue syndrome: exploration of a shared pathophysiology.

Hulens, Mieke, Rasschaert, Ricky, Vansant, Greet et al.·Journal of pain research·2018

This review paper proposes that ME/CFS, fibromyalgia, and a condition called idiopathic intracranial hypertension (IICH—where pressure builds up around the brain) may share similar underlying causes. All three conditions cause widespread pain, fatigue, cognitive problems, and other symptoms that could potentially be explained by increased pressure in the fluid surrounding the brain and spinal cord.

Pain and SensitizationCognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryMethods-PaperEditor reviewed

Self-regulatory fatigue in chronic multisymptom illnesses: scale development, fatigue, and self-control.

Nes, Lise Solberg, Ehlers, Shawna L, Whipple, Mary O et al.·Journal of pain research·2013

This study created a new questionnaire to measure a specific type of mental tiredness called self-regulatory fatigue—the exhaustion that comes from having to constantly manage your thoughts, emotions, and behaviors. Researchers gave this 18-question test to nearly 300 people with chronic illnesses like fibromyalgia and ME/CFS, along with standard fatigue and self-control tests. They found that this mental tiredness is related to, but distinct from, physical fatigue—suggesting it's a separate problem worth measuring and understanding.

Cognitive Impairment
E3 PreliminaryPEM not requiredModerate confidenceReview-NarrativeEditor reviewed

Fibromyalgia syndrome: a discussion of the syndrome and pharmacotherapy.

Smith, Howard S, Barkin, Robert L·American journal of therapeutics·2010

Fibromyalgia is a condition that causes widespread pain throughout the body, along with fatigue, sleep problems, brain fog, and mood changes. This article explains that fibromyalgia may share common features with ME/CFS and other conditions involving heightened pain sensitivity. While there is no cure, doctors can help manage symptoms through exercise, therapy, patient education, and specific medications.

Pain and SensitizationSleepCognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryCase-ControlEditor reviewed

Fibromylagia, chronic fatigue, and adult attention deficit hyperactivity disorder in the adult: a case study.

Young, Joel L, Redmond, Judith C·Psychopharmacology bulletin·2007

This study looked at patients who came to a psychiatry clinic with ADHD symptoms and also had unexplained tiredness and widespread pain—conditions similar to ME/CFS or fibromyalgia. When doctors treated the ADHD with medication, some patients noticed their fatigue and pain improved along with their attention problems. The researchers suggest this might mean these conditions involve how the brain processes information rather than problems in muscles and joints.

Cognitive Impairment
E3 PreliminaryPEM unclearPreliminaryReview-NarrativeEditor reviewed

Violence, stress, and somatic syndromes.

Crofford, Leslie J·Trauma, violence & abuse·2007

This review article examines how experiences of violence and stress may trigger or worsen conditions like ME/CFS, fibromyalgia, and irritable bowel syndrome—illnesses that involve pain, exhaustion, mood changes, memory problems, and sleep issues. The authors explain that stress affects the brain and body's hormone and nervous system function, which may make people more vulnerable to developing these conditions. Understanding this connection could help us recognize how violence exposure affects long-term health.

Pain and SensitizationSleepCognitive Impairment
E3 PreliminaryPEM unclearModerate confidenceReview-NarrativeEditor reviewed

Cognitive dysfunction in fibromyalgia and chronic fatigue syndrome: new trends and future directions.

Glass, Jennifer M·Current rheumatology reports·2006

Many people with fibromyalgia and chronic fatigue syndrome report problems with memory and thinking clearly. When researchers tested these patients' cognitive abilities, they found real difficulties with memory and how quickly patients process information. Brain imaging studies showed that patients' brains work differently during thinking tasks, requiring more activation than expected.

Cognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryReview-NarrativeEditor reviewed

Parallels between post-polio fatigue and chronic fatigue syndrome: a common pathophysiology?

Bruno, R L, Creange, S J, Frick, N M·The American journal of medicine·1998

This review examines similarities between fatigue experienced by polio survivors and people with ME/CFS, suggesting they may share common underlying brain problems. Both conditions involve difficulty concentrating, staying awake, and severe fatigue. The researchers propose that reduced dopamine (a brain chemical) and problems with specific brain systems might explain fatigue in both diseases.

Cognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryObservationalEditor reviewed

Neuropsychiatric sequelae of Nipah virus encephalitis.

Ng, Beng-Yeong, Lim, C C Tchoyoson, Yeoh, Alice et al.·The Journal of neuropsychiatry and clinical neurosciences·2004

This study followed 9 people who had Nipah virus brain inflammation for 2 years to see what happened to them afterward. Most developed psychiatric symptoms like depression or personality changes, and nearly all showed memory and attention problems. Interestingly, two patients developed chronic fatigue syndrome after their initial illness recovered.

Cognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryReview-NarrativeEditor reviewed

Exploring the arcuate fasciculus from a clinical perspective.

Shao, Zhi Ding, Gong, Yu Juan, Ren, Jing et al.·Frontiers in neuroscience·2023

This review examines a bundle of nerve fibers in the brain called the arcuate fasciculus, which helps connect language centers. Researchers found that several conditions—including ME/CFS, stroke, brain tumors, and others—can damage these nerve fibers in measurable ways. New brain imaging techniques can now visualize and measure this damage, which may help doctors understand what goes wrong and develop better treatments.

Cognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryMechanisticEditor reviewed

Study on the active components and mechanism of Suanzaoren decoction in improving cognitive impairment caused by sleep deprivation.

Cheng, Li, Wang, Fei, Li, Zi-Heng et al.·Journal of ethnopharmacology·2022

This study examined how an ancient Chinese herbal remedy called Suanzaoren Decoction (SZRD) might help improve thinking and memory problems caused by poor sleep. Researchers used computer analysis and laboratory experiments to identify the active ingredients in the herbs and understand how they work in the body, finding that the remedy may work through pathways related to estrogen in the brain.

SleepCognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryEditor reviewed

Building-related illness (BRI) in all family members caused by mold infestation after dampness damage of the building.

Kramer, Axel, Wichelhaus, Thomas A, Kempf, Volkhard et al.·GMS hygiene and infection control·2021

A family of five living in a house with severe mold damage all developed health problems. The mother developed symptoms very similar to ME/CFS, including extreme fatigue, cognitive problems, sleep issues, and respiratory complaints. After the family moved out, symptoms improved gradually—the father recovered in 2 weeks, the children in 6 months, and the mother took 18 months to fully recover.

SleepCognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryMechanisticEditor reviewed

Mental fatigue is linked with attentional bias for sad stimuli.

Watanabe, Kyosuke, Sasaki, Akihiro T, Tajima, Kanako et al.·Scientific reports·2019

When healthy people become mentally tired from doing difficult thinking tasks, their brains start paying more attention to sad and negative images. This study used computer tasks to measure how people's attention shifts before and after mental exhaustion. The findings suggest that fatigue changes how our brains process sad information, which may help explain why ME/CFS patients often struggle with mood-related challenges.

Cognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryRCTEditor reviewed

Treatment for Gulf War Illness (GWI) with KPAX002 (methylphenidate hydrochloride + GWI nutrient formula) in subjects meeting the Kansas case definition: A prospective, open-label trial.

Holodniy, Mark, Kaiser, Jon D·Journal of psychiatric research·2019

Researchers tested a combination treatment called KPAX002—containing a stimulant medication (methylphenidate) plus vitamins and nutrients meant to support energy production in cells—in 17 people with Gulf War Illness. After 12 weeks, patients reported about 25% improvement in their overall symptoms, including better fatigue, brain fog, sleep, and pain. The treatment was generally safe and well-tolerated, though a larger, more rigorous study is needed to confirm these results.

Pain and SensitizationSleepCognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryCase-ControlEditor reviewed

Fixed belief in cognitive dysfunction despite normal neuropsychological scores: neurocognitive hypochondriasis?

Boone, Kyle Brauer·The Clinical neuropsychologist·2009

Some people with ME/CFS report serious cognitive problems in their daily life, but when given standard memory and thinking tests, their scores are completely normal. This study presents one case and suggests that some patients may worry excessively about cognitive problems that aren't actually measurable on formal tests—a condition the author calls 'neurocognitive hypochondriasis.' The study notes this pattern may occur in ME/CFS and several other conditions.

Cognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryReview-NarrativeEditor reviewed

Possible links between behavioral and physiological indices of tiredness, fatigue, and exhaustion in advanced cancer.

Olson, Karin, Turner, A Robert, Courneya, Kerry S et al.·Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer·2008

This paper proposes a new framework for understanding tiredness and fatigue in advanced cancer patients. The researchers suggest that cancer and its treatments stress the body, which then affects four key systems: thinking ability, sleep quality, nutrition, and muscle strength. They propose that problems in all four of these areas together—not just one alone—are what cause severe fatigue, and that studying how these systems interact could lead to better treatments.

SleepCognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryLongitudinalEditor reviewed

Post concussion syndrome ebb and flow: longitudinal effects and management.

Rees, Roger J, Bellon, Michelle L·NeuroRehabilitation·2007

This study followed 20 adults who had lasting symptoms after a head injury (concussion) for an average of 3.35 years. Participants experienced fatigue, difficulty concentrating, mood changes, and sensitivity to noise. When they received counseling and therapy over two years, some symptoms like irritability improved, but many people still felt fundamentally changed and struggled with feelings of helplessness.

Cognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryEditorialEditor reviewed

Psychomotor speed: possibly a new marker for overtraining syndrome.

Nederhof, Esther, Lemmink, Koen A P M, Visscher, Chris et al.·Sports medicine (Auckland, N.Z.)·2006

This study proposes that measuring how quickly someone can respond to mental tasks (psychomotor speed) might help identify athletes who are overtraining before serious problems develop. The researchers noticed that overtraining syndrome shares some features with chronic fatigue syndrome and depression, both of which involve slowed mental processing, and suggest this slowness could be an early warning sign.

Cognitive Impairment
E3 PreliminaryPEM unclearPreliminaryReview-NarrativeEditor reviewed

Cognitive and mood disturbance as causes and symptoms of fatigue in cancer patients.

Valentine, A D, Meyers, C A·Cancer·2001

This review discusses how fatigue, brain fog, and depression are connected in cancer patients and how they may cause or worsen each other. The authors suggest that understanding these connections might help doctors develop better, more personalized treatments that address the specific needs of each patient.

Cognitive Impairment
E0 ConsensusPEM not requiredModerate confidenceMeta-AnalysisMachine-drafted

[Efficacy and safety of fonturacetam in asthenia: a systematic review and meta-analysis].

Devlikamova, F I, Safina, D R·Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova·2025

This review combined results from 11 studies testing a medication called fonturacetam (also known as Actitropil) in people with asthenia—a medical term for persistent exhaustion and lack of energy. After one month of treatment at 200 mg daily, patients reported significantly less fatigue, with improvements also seen in sleep, mood, thinking ability, and overall quality of life. About 5.5% of patients experienced mild, temporary side effects that went away within a week.

SleepCognitive Impairment
E2 ModeratePEM unclearModerate confidenceCross-SectionalMachine-drafted

Cognitive dysfunction in adolescents with chronic fatigue: a cross-sectional study.

Sulheim, Dag, Fagermoen, Even, Sivertsen, Øyvind Stople et al.·Archives of disease in childhood·2015

This study compared thinking and memory skills in teenagers with chronic fatigue to healthy teenagers. Teenagers with chronic fatigue performed worse on tests of processing speed (how fast they could think), working memory (holding information in mind), and learning new information. These differences were not explained by depression, anxiety, or sleep problems alone.

Cognitive Impairment
E2 ModeratePEM unclearModerate confidenceCross-SectionalMachine-drafted

Deficits of interference control in adolescents with chronic fatigue syndrome.

van de Putte, Elise M, Böcker, Koen B, Buitelaar, Jan et al.·Archives of pediatrics & adolescent medicine·2008

This study looked at how well teenagers with ME/CFS could focus and filter out distractions compared to healthy teenagers. Researchers used brain activity tests to see if adolescents with ME/CFS had difficulty with tasks requiring concentration and filtering out irrelevant information. The findings suggest that ME/CFS in teenagers may affect how the brain controls attention and handles competing information.

Cognitive Impairment
E2 ModeratePEM unclearModerate confidenceObservationalMachine-drafted

From good health to illness with post-infectious fatigue syndrome: a qualitative study of adults' experiences of the illness trajectory.

Stormorken, Eva, Jason, Leonard A, Kirkevold, Marit·BMC family practice·2017

This study followed 26 adults in Norway who developed severe fatigue and other symptoms after a water contamination outbreak caused by a parasite. Researchers interviewed these patients about how their illness developed and affected their daily lives. Everyone described similar patterns: getting worse over time, reaching a lowest point, then gradually improving—but none returned to their pre-illness health, and most had to stop working or studying.

Cognitive Impairment
E3 PreliminaryPEM unclearPreliminaryMachine-drafted

Is Cognitive Change Necessary to Alleviate Symptoms in Patients With Functional Somatic Syndrome?

Maroti, Daniel, Johansson, Robert·Frontiers in psychiatry·2021

This study examined whether changing how patients think about their symptoms (cognitive change) is necessary to improve symptoms in people with functional somatic syndromes like ME/CFS. The researchers explored the relationship between psychological thinking patterns and symptom improvement to understand better which approaches might help patients feel better.

Cognitive Impairment
E3 PreliminaryPEM unclearPreliminaryReview-NarrativeMachine-drafted

[Modern approaches to diagnosis and treatment of postinfectious asthenic syndrome in children].

Nemkova, S A·Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova·2025

This review article discusses postinfectious asthenic syndrome—a condition causing severe tiredness and weakness that develops after infections like colds, flu, and COVID-19 in children and teenagers. The authors examine how this condition develops, its symptoms, and how a medication called Mexidol may help reduce fatigue and improve thinking, mood, and nervous system problems that often accompany it.

Autonomic Nervous SystemCognitive Impairment
E3 PreliminaryPEM unclearPreliminaryCross-SectionalMachine-drafted

The neuropsychological dimensions of postinfectious neuromyasthenia (chronic fatigue syndrome): a preliminary report.

Altay, H T, Toner, B B, Brooker, H et al.·International journal of psychiatry in medicine·1990

This study looked at whether ME/CFS patients who reported memory and concentration problems actually showed these difficulties when tested. Surprisingly, the patients performed better than average on standard cognitive tests, even though they felt they had cognitive problems. The researchers suggested that psychological factors might explain why patients' subjective experience didn't match their test results.

Cognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryReview-NarrativeMachine-drafted

Macrophagic myofasciitis-associated dysfunctioning: An update of neuropsychological and neuroimaging features.

Aoun Sebaiti, Mehdi, Abrivard, Marie, Blanc-Durand, Paul et al.·Best practice & research. Clinical rheumatology·2018

Macrophagic myofasciitis (MMF) is a condition where aluminum particles from vaccines remain in muscle tissue and trigger long-term inflammation and immune system problems. People with MMF often experience fatigue, joint and muscle pain, and cognitive difficulties like trouble concentrating and memory problems. Brain imaging shows abnormalities in specific regions, suggesting these cognitive problems are caused by actual changes in the brain.

Cognitive Impairment

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