Longitudinal Epidemiology

P1 Abstract The novel coronavirus, SARS-CoV-2, spread worldwide, resulting in devastating consequences. Our preliminary data and several published studies strongly suggest that, in adults over 60 years of age, post- infectious cognitive impairment is present in nearly half of affected people, potentially regardless of the severity of acute COVID-19 illness. Given the already alarming and increasing numbers of persons with Alzheimer's dementia and related dementias (ADRD) globally, it is essential that we investigate and understand the degree and manner and in which SARS-CoV-2 may place older persons at higher risk of progressive cognitive decline and even ADRD. We have put together an international consortium of investigators uniquely poised to collect and analyze a broad range of high quality clinical, biomarker, genome, and neuroimaging data. The study, entitled Interaction between SARS-CoV-2 Infection and Ancestral genomic Variations in the Risk of Alzheimer's Disease (ISAVRAD), proposes a five-site, international, two-arm (patients and controls), longitudinal (baseline, 18 and 36-months) design enrolling 4,300 individuals with and without history of SARS- CoV-2. Project 1 of ISAVRAD will describe the longitudinal course, epidemiological risk/resiliency factors, and environmental interactions predictive of cognitive decline and progress to ADRD following SARS-CoV-2 infection in adults over 60 years of age from ancestral and admixed populations. Specifically, Project 1 will longitudinally compare the rate of cognitive decline in older adults with and without exposure to SARS-CoV-2 infection (Aim 1). We hypothesize that cognitive changes will be progressive in nature and increase rates of ADRD based on Clinical Dementia Rating scores and neurocognitive performance. For the infected group, we will compare outcomes by severity of COVID-19 symptoms and the presence and severity of anosmia, under the hypothesis that that hyposmia/anosmia, but not acute COVID-19 severity, will predict the presence and likelihood of progression of cognitive impairment and ADRD (Aim 2). Finally, working with the Neuroimaging,and Projects 2 and3, we will identify predictors of SARS-CoV-2-induced cognitive decline. We hypothesize that specific symptoms (anosmia-hyposmia) will segregate with related neuroimaging changes (in the olfactory cortical network) and risk will be influenced by genetic ancestry to predict the highest risk of cognitive decline and new onset ADRD (Aim 3).