Cognitive, Neural, and Immunological Consequences of COVID-19 in Older African Americans and How They Relate to Risk for Alzheimer’s Disease

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PROJECT SUMMARY/ABSTRACT Alzheimer's Disease (AD) and COVID-19 share multiple common features including (1) disruption to the immune system; (2) disruption to the hippocampus, a key brain structure within the medial temporal lobe; (3) age being a risk factor for both AD and severe morbidity and mortality from COVID-19. As such, a clearer understanding of how COVID-19 impacts cognition, neural function, and risk for AD may lead to new insights that inform future research on how age-related decline and dysfunction in the immune system may play a causal role in the etiology and pathology of Alzheimer's disease. Furthermore, Older African Americans have exceptionally high rates of death or severe health consequences if they are exposed to the SARS-CoV-2 virus—the causative infectious agent for COVID-19. Behavioral and lifestyle factors—including low levels of physical activity, poor cardiovascular fitness, high rates of obesity and elevated levels of stress—may be contributing to this increased COVID-19 mortality in some older African Americans, much as they are generally acknowledged to be potential contributors to high rates of AD in African Americans. This one year administrative supplement seeks to understand the links between COVID-19 and AD in African Americans by addressing three key questions: (1) Are changes in the immunological health of people who have been infected with SARS-CoV-2 associated with increases in behavioral and neural risk markers for AD, as well as longer-term higher risk for future conversion to amnestic mild cognitive impairment (aMCI) and AD. (2) Does COVID-19, including mild or asymptomatic infection, cause lasting functional disruption to neural networks within the medial temporal lobe and hippocampus, and, if so, are these associated with measurable cognitive deficits? (3) Why do some older African Americans suffer far worse outcomes from COVID-19 than their peers, and what are the long-term brain health consequences of COVID-19 for older African Americans. With this supplemental funding we will expand the parent grant methods to collect blood from (a) 100 of our past participants who are scheduled to return in 2020-2021 for their 2-year or 4-year follow up visits as part of the existing parent grant protocol, plus (b) 100 new individuals with a history of SARS-CoV-2 infection. All participants will be administered both the full current R01 protocol (health, fitness, cognitive, and optional brain imaging) as well as the new COVID-19 and immunology assessments. The initial cross-sectional analysis (Aims 1 and 2) will evaluate (1) whether a prior SARS-CoV-2 infection is associated with cognitive and neural network dysfunction, specifically related to the medial temporal lobe, similar to what we have seen in those at high risk of being in a preclinical phase of AD and, (2) the degree to which cognitive and neural impairments correlate with a dysfunctional immune system, specifically CD8+ T cell senescence. This will lead up to the longitudinal analysis (Aim 3) assessing whether or not SARS-CoV-2 infection in older African Americans is associated with a higher rate of cognitive decline and conversion to aMCI or AD.