Dr. Katharine Seton is a research fellow at the Quadram Institute in Norwich, England, a research center that focuses on how food and microbes affect health and disease. She specializes in studying how microbes in the guts of people with ME/CFS relate to this disease. Since winning her Ramsay Research Grant in 2022, Dr. Seton published five articles on ME/CFS, including studies on how gut viruses or autoantibodies to gut tissues contribute to symptoms.
In her most recent review article, in the International Journal of Molecular Sciences, Dr. Seton collaborated with her colleagues (Dr. Smolak Bansal, Spire Bushey Hospital, UK; Dr. Jonathan Brooks, University of Liverpool, UK; and Dr. Simon Carding, Norwich Medical School, UK) to review another important topic for people with ME/CFS—how ME/CFS can bring about cognitive dysfunction and how we may treat people to reduce cognitive dysfunction. About nine in ten people with ME/CFS have significant trouble concentrating, processing information, and remembering things. This cognitive dysfunction often substantially affects their work and personal lives, sometimes to incapacitating levels.
The team reviewed several factors that contribute to ME-CFS–associated cognitive dysfunction—neuroinflammation, muscle dysfunction, viral infection, autoimmunity, poor sleep, and others. The brains of people with ME/CFS may get warmer and have higher levels of key metabolites—these are signs of neuroinflammation (the brain responding to infection or injury). Inflammatory cytokines may dysregulate blood flow to the brain, and brain tissues can swell or shrink. In people with ME/CFS, this sometimes happens to brainstem tissues (important for attention and learning) or to the amygdala (important for memory, emotions, and making decisions). Inflammatory cytokines may also weaken signals among these tissues. Weakened signals in the brainstem correlate with worse cognition in adults with ME/CFS.
If people with ME/CFS become more sedentary, then their weakened muscles may produce less brain-derived neurotrophic factor, slowing brain-cell growth. Viruses can infect brain cells directly and stimulate them to make inflammatory cytokines, which change neurotransmitter levels and reduce cognition. For example, the Epstein-Barr Virus protein dUTPase can reduce dopamine and serotonin levels. In some people with ME/CFS, the higher the levels of antibodies against dUTPase, the worse the symptoms. Finally, many people with ME/CFS have trouble sleeping, and restorative sleep is critical for cognitive function.
The team noted that up to a third of people with Long Covid have poor cognition. Thus, some mechanisms that impair cognition in people with ME/CFS may apply to people with Long Covid too.
Dr. Seton’s team also reviewed treatments that improve cognition for people with ME/CFS. For those whose ME/CFS symptoms are driven by inflammation, anti-inflammatory drugs may help. For those whose symptoms are driven by poor sleep, melatonin may work (perhaps in combinations with palmitoylethanolamide, as used to treat people with fibromyalgia).
Other useful treatments include Ampligen (an immune stimulant); aripiprazole (an antidepressant that increases dopamine); L-carnitine, CoQ10, glycerol, guanidinoacetic acid, and NADH (which all promote ATP and serotonin levels); and immunoadsorption (which reduces autoimmunity by removing B cells, including B cells targeting autonomic receptors).
Dr. Seton pointed out future work needed to clarify how ME/CFS affects cognition and how to reduce this symptom. Earlier studies on cognitive dysfunction in ME/CFS used incomplete data sets or irregular treatments, or they included people with other mental health conditions (for example, depression or anxiety). Future clinical trials must consider missing data, ensure regular treatments, and account for comorbidities related to cognitive dysfunction. Especially important is studying how newer sleep medicines help people with ME/CFS, Dr. Seton said.
