Evidence browser

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.

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.

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.

Autonomic Nervous SystemCognitive Impairment

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.

E2 ModerateCohortPEM unclearObservational

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.

E2 ModerateCohortPEM not required

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.

E2 ModerateCohortPEM not requiredObservational

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 ModerateCohortPEM not requiredObservational

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 ModerateCohortPEM requiredCross-Sectional

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

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 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.

E2 ModerateCohortPEM unclearLongitudinal

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.

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.

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.

E2 ModerateCohortPEM requiredCross-Sectional

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

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.

E2 ModerateCohortPEM unclearCase-Control

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.

E2 ModeratePEM unclearRegistry-Resource

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

E2 ModerateBehavioralPEM not requiredCross-Sectional

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.