Post COVID-19 Neuro-Cognitive Manifestations and Underlying Mechanisms in Older African Americans

There are significant racial disparities in COVID-19 infection, morbidity, and mortality rates, with African Americans and older adults especially vulnerable to having poor outcomes. It is now apparent that the impact of COVID-19 persists beyond the acute infection period, and that 'long haulers' (i.e., persons > 4 weeks post- acute infection) continue to experience symptoms that negatively affect their activities of daily living and quality of life. Of these sequelae, the prevalence, phenotypes, and longitudinal course of post-acute COVID-19 cognitive impairments (PCCI) have not been systematically investigated. There is a need to characterize and to identify risk factors and mechanisms responsible for these long term impairments, especially in older adult African Americans who by virtue of their high prevalence of disease-specific comorbidities and socioeconomic risk factors, are a particularly vulnerable group for neurocognitive sequelae and neurodegenerative brain diseases including Alzheimer's disease and related disorders. We propose a prospective longitudinal study of PCCI in 407 African Americans 50 years and older with a history of COVID-19 infection (symptomatic or asymptomatic). Participants will receive comprehensive assessments including cognitive testing, neuroimaging, cardiovascular evaluation (endothelial function, 6-minute walk test, ECG monitoring) and biospecimen collection and analyses including blood and cerebrospinal fluid (Apolipoprotein-e, coagulopathy, viral immunity and proteomic measures of inflammation, neurodegeneration, and other pathways). Aim 1 will characterize the neuropsychological profiles and the longitudinal course of PCCI in older African Americans, and test the hypothesis that attention, memory, and executive functioning are most affected. In Aim 2, we will determine factors associated with prevalent PCCI at study baseline and their persistence in older African Americans, with the prediction that risk factors such as older age, multiple comorbidities, and poor social determinant of health indicators are associated with prevalent and persistent/progressive PCCI. Aim 3 will determine molecular, cardiovascular and neuroimaging characteristics related to prevalent and persistent or progressive PCCI in older African Americans, with the hypothesis that higher levels of systemic and neuro- inflammation, pro-atherothrombotic state, APOe4 allele and AD biomarker pathology, impaired peripheral and cerebral endothelial function and measures of brain connectivity are related to prevalent and persistent or progressive PCCI. We expect that the findings of this study will have a positive impact in guiding clinical decision making and informing public health policy.