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ME/CFS Atlas — A public knowledge atlas for ME/CFS

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ME/CFS Atlas is an evidence reference platform, not a medical provider. Content is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

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ME/CFS Evidence Browser — Classified Studies on Myalgic Encephalomyelitis

Evidence browser

Search and filter 6,167 studies by evidence level, diagnostic criteria, PEM status, and research domain. Each entry links to the original source.

Studies sorted by evidence level, then year. Browse by topic instead →

Evidence level (E0–E3) reflects study type and replication, not methodological quality. A weak systematic review still sits at E0. How evidence levels work →

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397 studies

E0 — Consensus643E1 — Replicated320E2 — Moderate2,782E3 — Preliminary2,422

ME/CFS4,025Long COVID217Post-infectious189Overlapping1,050

Required for diagnosis414Not specified / unclear2,219Not required3,534

Post-Exertional Malaise1,064Cognitive Dysfunction1,735Pain1,620Unrefreshing Sleep799Orthostatic Intolerance478

Cytokines818Gene Expression567Metabolomics473Neuroimaging468Autoantibodies458

Infection-Triggered1,174Long COVID Overlap588Pediatric493Severe231

Strong Phenotyping438Sex-Stratified326Severe ME Included118

Systematic Review265Meta-Analysis60RCT300

Peer-reviewed6,110Preprint3Unclear54

261–280 of 397 studies

E2 ModerateBehavioralPEM not requiredCross-Sectional

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 ModerateBehavioralPEM not requiredCross-Sectional

[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 ModerateCohortPEM not requiredCross-Sectional

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 ModerateCohortPEM not requiredCross-Sectional

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 ModerateCohortPEM not requiredCross-Sectional

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 ModerateCohortPEM not requiredCross-Sectional

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 ModerateCohortPEM not requiredCross-Sectional

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 ModerateCohortPEM not requiredCross-Sectional

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 ModerateBehavioralPEM not requiredCross-Sectional

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 ModerateCohortPEM not requiredCross-Sectional

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 ModerateCohortPEM not requiredCross-Sectional

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 ModerateCohortPEM not requiredCross-Sectional

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 ModerateCohortPEM not requiredCross-Sectional

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 ModerateCohortPEM not requiredCross-Sectional

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 ModerateCohortPEM not requiredCross-Sectional

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 ModerateBehavioralPEM not requiredCross-Sectional

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 ModerateCohortPEM not requiredCross-Sectional

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 ModerateBehavioralPEM unclearCross-Sectional

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 ModerateCohortPEM unclearCross-Sectional

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 ModerateCohortPEM not requiredCase-Control

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

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PEM Immune Neuro Metabolic Biomarkers Severe ME Long COVID Cognitive

Curated Collections

Thematic groupings by clinical question or research area.

Neuroinflammation Evidence

PET imaging and other studies providing evidence for brain inflammation in ME/CFS.

Metabolism & Mitochondria

Metabolomics and mitochondrial function studies revealing energy metabolism disruption.

Biomarkers

Studies identifying potential biological markers for ME/CFS diagnosis and stratification.

PEM-Specific Research

Studies specifically examining post-exertional malaise, the hallmark symptom of ME/CFS.