Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is characterized by persistent physical and mental fatigue. The post-COVID-19 condition patients refer physical fatigue and cognitive impairment sequelae. Given the similarity between both conditions, could it be the same pathology with a different precipitating factor? Objective: To describe the cognitive impairment, neuropsychiatric symptoms, and general symptomatology in both groups, to find out if it is the same pathology. As well as verify if the affectation of smell is related to cognitive deterioration in patients with post-COVID-19 condition. Methods: The sample included 42 ME/CFS and 73 post-COVID-19 condition patients. Fatigue, sleep quality, anxiety and depressive symptoms, the frequency and severity of different symptoms, olfactory function and a wide range of cognitive domains were evaluated. Results: Both syndromes are characterized by excessive physical fatigue, sleep problems and myalgia. Sustained attention and processing speed were impaired in 83.3% and 52.4% of ME/CFS patients while in post-COVID-19 condition were impaired in 56.2% and 41.4% of patients, respectively. Statistically significant differences were found in sustained attention and visuospatial ability, being the ME/CFS group who presented the worst performance. Physical problems and mood issues were the main variables correlating with cognitive performance in post-COVID-19 patients, while in ME/CFS it was anxiety symptoms and physical fatigue. Conclusions: The symptomatology and cognitive patterns were similar in both groups, with greater impairment in ME/CFS. This disease is characterized by greater physical and neuropsychiatric problems compared to post-COVID-19 condition. Likewise, we also propose the relevance of prolonged hyposmia as a possible marker of cognitive deterioration in patients with post-COVID-19.

The loss of olfactory stimulation correlates well with at least 68 widely differing neurological disorders, including depression, and we raise the possibility that this relationship may be causal. That is, it seems possible that olfactory loss makes the brain vulnerable to expressing the symptoms of these neurological disorders, while daily olfactory enrichment may decrease the risk of expressing these symptoms. This situation resembles the cognitive reserve that is thought to protect people with Alzheimer’s neuropathology from expressing the functional deficit in memory through the cumulative effect of intellectual stimulation. These relationships also resemble the functional response of animal models of human neurological disorders to environmental enrichment, wherein the animals continue to have the induced neuropathology, but do not express the symptoms as they do in a standard environment with restricted sensorimotor stimulation.

The societal burden of Alzheimer’s Disease (AD) and other major forms of dementia continues to grow, and multiple pharmacological agents directed towards modifying the pathological “hallmarks” of AD have yielded disappointing results. Though efforts continue towards broadening and deepening our knowledge and understanding of the mechanistic and neuropathological underpinnings of AD, our previous failures motivate a re-examination of how we conceptualize AD pathology and progression. In addition to not yielding effective treatments, the phenotypically heterogeneous biological processes that have been the primary area of focus to date have not been adequately shown to be necessary or sufficient to explain the risk and progression of AD. On the other hand, a growing body of evidence indicates that lifestyle and environment represent the ultimate level of causation for AD and age-related cognitive decline. Specifically, the decline in cognitive demands over the lifespan plays a central role in driving the structural and functional deteriorations of the brain. In the absence of adequate cognitive stimulus, physiological demand–function coupling leads to downregulation of growth, repair, and homeostatic processes, resulting in deteriorating brain tissue health, function, and capacity. In this setting, the heterogeneity of associated neuropathological tissue hallmarks then occurs as a consequence of an individual’s genetic and environmental background and are best considered downstream markers of the disease process rather than specific targets for direct intervention. In this manuscript we outline the evidence for a demand-driven model of age-related cognitive decline and dementia and why it mandates a holistic approach to dementia treatment and prevention that incorporates the primary upstream role of cognitive demand.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is believed to affect central nervous system functions through various indirect, and possibly direct, mechanisms. We are only now beginning to understand the possible effects of the virus on human cognition. This review summarizes extant yet limited literature on clinical neuropsychological findings in adult coronavirus disease 2019 (COVID-19) patients and survivors. Neuropsychological outcomes were often in the form of cognitive screen results, although various studies administered comprehensive batteries. With respect to screens, the Montreal Cognitive Assessment appeared relatively sensitive to cognitive dysfunction associated with COVID-19. Patients and survivors presented with weaknesses on screens and comprehensive batteries, although the pattern of these weaknesses was not specific to etiology. Broadly, weaknesses were suggestive of executive dysfunction, although more than one study did not detect significant impairment. Weaknesses should be interpreted cautiously due to potential confounds/contributing factors (weaknesses may partly reflect psychiatric sequelae; weaknesses may be over-interpreted due to inadequate assessment of premorbid functioning). Studies reported different approaches in defining impairment, likely contributing to variable findings. The current review discusses ongoing efforts to harmonize approaches to evaluating neuropsychological functioning globally, as well as emphasizes taking a comprehensive approach towards understanding how the disease affects cognition.