Cognitive Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-Aetiology and Potential Treatments.
Bansal, Amolak Singh, Seton, Katharine A, Brooks, Jonathan C W et al. · International journal of molecular sciences · 2025 · DOI
Quick Summary
Many ME/CFS patients experience brain fog and difficulty concentrating, which can be as disabling as physical symptoms. This review examined how ongoing low-level inflammation and viral activity in the body may damage thinking and memory by affecting blood flow and nerve function in the brain. The researchers suggest that treating inflammation, controlling viral reactivation, and improving how cells produce energy could potentially help restore cognitive function.
Why It Matters
Cognitive dysfunction affects quality of life significantly in ME/CFS yet remains poorly understood and undertreated. This comprehensive review integrates multiple mechanistic pathways, providing a framework for understanding brain fog and directing future therapeutic strategies. It validates the neurological basis of cognitive symptoms and identifies potential intervention targets—inflammation reduction, viral reactivation prevention, and mitochondrial support.
Observed Findings
Systemic infection and peripheral inflammation are associated with impaired attention and cognitive function in ME/CFS patients.
Pro-inflammatory cytokines are elevated in ME/CFS and may contribute to altered regional cerebral blood flow.
Immune dysregulation in ME/CFS manifests as both subtle immunodeficiency and potential autoimmune targeting of neuronal receptors.
Mitochondrial dysfunction may underlie both fatigue and cognitive impairment in ME/CFS.
Cognitive dysfunction co-occurs with markers of persistent viral reactivation in some ME/CFS populations.
Inferred Conclusions
Low-grade persistent inflammation is a plausible central mechanism linking systemic dysfunction to cognitive impairment in ME/CFS.
Multiple pathways—inflammatory, autoimmune, and bioenergetic—likely contribute to cognitive dysfunction, suggesting multi-targeted treatment approaches may be necessary.
Therapeutic strategies addressing inflammation, viral reactivation, and mitochondrial function warrant investigation as potential treatments for cognitive dysfunction.
Remaining Questions
Which specific pro-inflammatory cytokines most directly impair cognition, and are they viable biomarkers for cognitive dysfunction severity in ME/CFS?
What This Study Does Not Prove
This review does not establish causation; it identifies plausible mechanisms and correlations between inflammation and cognition. It does not provide definitive evidence that any single mechanism is primary or that proposed treatments will be effective. The review cannot confirm which inflammatory markers or immune abnormalities are most relevant to individual patients' cognitive symptoms.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
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Does immune dysregulation cause cognitive impairment, or do they share a common upstream cause?
Which therapeutic interventions—anti-inflammatory, antiviral, or mitochondrial support—are most effective for improving cognitive function, and in which patient subgroups?
How reversible is cognitive dysfunction once the underlying inflammatory or viral mechanisms are addressed?