Topic

Cognitive Impairment

Domain: Neurology

PEM-relevant research

7 studies in the atlas

Brain fog, working memory deficits, and processing speed reductions in ME/CFS.

What We Know

Neuropsychological testing consistently reveals reduced information processing speed, working memory deficits, and attention difficulties in ME/CFS. These correlate with reduced cerebral blood flow in upright posture.

What We Think

Real-world cognitive testing via smartphones and fMRI studies during cognitive challenges are providing new insights.

What We Don't Know

Cognitive impairment mechanisms in ME/CFS are multifactorial — neuroinflammation, reduced cerebral perfusion, and sleep disruption all contribute. Disentangling causes is difficult.

Studies in this Topic

E0 ConsensusPEM ✓Moderate confidenceReviewed

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.

BiomarkersCognitive ImpairmentPost-Exertional MalaiseImmune Dysregulation

E0 ConsensusPEM ✓Higher confidenceReviewed

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 ✓Moderate confidenceReviewed

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.

Cognitive ImpairmentPost-Exertional MalaiseImmune Dysregulation

E0 ConsensusPEM ✓Moderate confidenceMachine draft

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.

Cognitive ImpairmentPost-Exertional MalaiseImmune Dysregulation

E1 ReplicatedPEM ✓Moderate confidenceReviewed

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

E3 PreliminaryPEM ✓PreliminaryReviewed

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 ✓PreliminaryReviewed

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.

BiomarkersCognitive ImpairmentPost-Exertional MalaiseImmune Dysregulation