Interactions of SARS-CoV-2 infection and genetic variation on the risk of cognitive decline and Alzheimer’s disease in Ancestral and Admixed Populations

The science proposed in this program takes advantage of the unique scientific opportunity created by the ongoing coronavirus pandemic, to study the interaction between a definable and time-limited risk-inducing environmental event (exposure to the virus) and genomic variation on the occurrence of cognitive decline and Alzheimer’s disease and related dementias (ADRD) in large cohorts of older adults from underrepresented minorities in the USA and ancestral groups in Africa and South America. The investigators leading the program have extensive experience in directing international consortia and longitudinal cohorts, including the creation and follow up of an Amerindian cohort in the Andes region for longer than a decade. We have pilot ascertainment of cognitive impairment end-points in newly recruited older adults of Amerindian ancestry. This U19 will investigate the interactions between whole genome sequence genetic variations and COVID-19 infection and disease on the risk of cognitive decline and risk of ADRD in 4,300 individuals as part of newly recruited cohorts in Texas, New York, Washington State, Ibadan (Nigeria), and Jujuy (Argentina). Participant assessments will include neurological, cognitive, imaging and blood-based biomarker evaluations using harmonized protocols and at 3 time points: within a few months of infection and 18 and 36 months afterwards. We propose to answer this complex research question with 3 highly integrated Projects supported by equally integrated Administrative, Clinical, Neuroimaging and Data Management/Statistics Cores. All projects involve integrated multidisciplinary teams of investigators within a consortium of institutions including University of Texas Health San Antonio, University of Texas Rio Grande Valley, Washington University School of Medicine, Albert Einstein College of Medicine, University of Washington, University of Ibadan, the Ministry of Health of the Province of Jujuy (Argentina) and the FULTRA Foundation (Argentina). Resources and study expertise will be tightly coordinated across multiple sites and Cores, and integrated to the National Institute of Aging Alzheimer’s Disease Sequencing Project and National Alzheimer’s Coordinating Center which will help ensure optimal sharing of the acquire data and knowledge.