PROJECT SUMMARY/ABSTRACT Our long-term goal is to employ innovative community based participatory research to establish a community advisory board, to collaborate with our community partners to recruit, enroll, and retain a cohort of Black participants and, then, to examine causal mechanisms that increase the risk of Alzheimer disease (AD) within the community cohort. The long preclinical stage of AD, as reflected in biomarkers among adults, is a key risk factor of symptomatic AD. However, despite Blacks having a higher risk of developing AD, recent studies suggest that they have less abnormal levels of biomarkers than Whites in cognitively normal samples. This study aims to examine other risk factors of cognitive decline and AD such as depression, stress, and social determinants of health (SDOH) in a representative sample of Black participants. This research is significant because there are nearly 46 million Black Americans, comprising 13% of the population in the United States. The Black older adult population is expected to increase, from 4.4 million older adults in 2016 to 12.1 million by 2060. Despite these demographic projections, Blacks are significantly underrepresented in AD research. An almost exclusive focus on Whites has created a knowledge gap in understanding how SDOH mechanisms affect diverse populations. Closing this knowledge gap soon is critical since epidemiological studies suggest that Blacks are at twice the risk of AD compared to Whites. Our Specific Aims will (1) Establish a cohort of middle-to-older age Black adults (N=300) using community- based participatory research to understand the unique social, environmental, and economic barriers related to AD risk, (2) Determine the impact of depression, stress, and a novel, theory-based SDOH composite index (CI) on cognitive functioning in participants who are cognitively normal with and without preclinical AD, and (3) Test the association between white matter hyperintensities (WMH) and hippocampal volume (HV) with the SDOH-CI in a subset of participants (N=150) with magnetic resonance imaging (MRI) data. To test our Aims, we have assembled a multidisciplinary team with expertise in AD, SDOH, community- based participatory research and system dynamics, community mobilization, stress and depression, plasma biomarkers, genetics, neuroimaging, neuropsychology, and biostatistical methods. Participants will undergo a one-time blood draw for AD biomarker profiling, cognitive assessment using a neuropsychological battery, and participate in one MRI scan session. Participants will also participate in workshops, complete a comprehensive battery of SDOH measures mapped onto the National Institute of Aging’s Health Research Disparities Framework, and clinical, neurological, and neuropsychological tests annually for up to five years. Once obtained, this knowledge of how within-group heterogeneity in cognitive functioning and AD risk is impacted by SDOH may better support effective AD in...