Project Summary African Americans (AAs) have disproportionately higher rates and earlier onset of Alzheimer’s disease and related dementias (ADRD) relative to White Americans. Although prior research has made significant contributions to our understanding of racial disparities in ADRD, we still lack a comprehensive understanding of how the individual lived experience of being AA, including cumulative exposure to structural racism, contributes to elevated ADRD risk and the potential mechanisms underlying those risks. Building on the existing, community-based research infrastructure developed by our team’s previously funded studies, we will follow a cohort of residents (n=1133) living in two historically disinvested, predominantly AA communities to understand how dynamic neighborhood socioeconomic conditions across the lifecourse contribute to cognitive outcomes in mid- and late-life adults. This proposal rests on the premise that neighborhood segregation and subsequent disinvestment contributes to poor cognitive outcomes for AAs via factors including a) lower access to educational opportunities and b) higher exposure to race- and socioeconomically-relevant stressors, including discrimination, trauma, and adverse childhood events. In turn, these cumulative exposures foster psychological vigilance in residents, leading to cardiometabolic dysregulation and sleep disruption, which may mediate associations between neighborhood disadvantage and ADRD risk. We also will examine potential protective factors that may promote cognitive health, including neighborhood social cohesion, safety, and satisfaction. The proposed study will leverage our existing longitudinal data on risk and protective factors, biobehavioral mediators, and baseline cognitive assessments, and will include: 1) three waves of cognitive assessments in the full cohort of participants who are 50 years+ (participants who are aged 35-49 years will have two assessments) and clinical adjudication of ADRD in participants who are 50+ (n=906), 2) additional assessments of blood pressure and objective sleep, 3) a comprehensive assessment of life and residential history using the questionnaire from the Health and Retirement Study (HRS); and 4) in-depth qualitative interviews to reveal lifecourse opportunities and barriers experienced by AAs in achieving optimal cognitive health in late life. Understanding how structural racism has influenced the lived experience of AAs including dynamic changes in neighborhood conditions over time is critical to inform multi-level intervention and policy efforts to reduce pervasive racial and socioeconomic disparities in ADRD.