The Role of Neighborhood Social Exposome Dynamics in Risk and Resilience to Alzheimer's Disease and Related Dementias - Alzheimer’s disease and related dementias (ADRD) are a leading cause of death with considerable economic and human costs. Although there have been substantial advancements in anti-amyloid therapies to help slow the progression of Alzheimer’s disease, the most effective approach to reduce the risk of ADRD is through primary prevention, including the promotion of physical activity, healthy diet, cardiovascular risk monitoring and control, and social and cognitive engagement. Several promising multi-domain behavioral intervention trials are underway to change behaviors related to these risks, yet decades of behavior change research has demonstrated the challenges of sustaining behavior change after the intervention has ended. Rather, health promoting behaviors are commonly supported or undermined by the social exposome – the holistic social, psychosocial, and sociodemographic exposures at individual and contextual levels that are ever-present across the lifecourse and affect human development and health. Several recent studies have shown that social exposome exposures – especially neighborhood-level disadvantage – are associated with ADRD risk. However, the social exposome is not static; the social contexts of neighborhoods have changed dramatically over the past several decades. No studies to date have explored the importance of dynamic changes in the social exposome for ADRD risk and related disparities. To interrogate the role of neighborhood social exposome change for primary prevention of ADRD, the proposed study will investigate the pathways between 30 years of neighborhood-level social exposome change, individual modifiable ADRD risk factors that are common prevention targets via behavioral change, and late-life cognitive/brain health outcomes in three NIH-funded cohorts: The Kaiser Health Aging and Life Experiences Study (R01AG052132, MPI: Whitmer, Gilsanz, Glymour, Mayeda); the Study of Healthy Aging in African Americans (R01AG050782 MPI: Whitmer, Gilsanz); and Life After 90 (R01AG056519, MPI: Whitmer, Corrada, Gilsanz). This research supports NIA’s strategic goals by “illuminat(ing) the pathways by which social, psychological, economic, and behavioral factors affect health,” and “understand(ing) environmental, social, cultural, behavioral, and biological factors that create and sustain health disparities.” Translating evidence regarding health behavior change to population-based initiatives without accounting for the social exposome will have a truncated impact on ADRD risk reduction. Accordingly, findings from the proposed research will provide critical insights for public health practitioners, policy experts, urban planners, and other community leaders to enhance key social exposome factors that facilitate health promoting behavior in the community, thereby advancing population-based strategies for primary prevention of ADRD that also help to reduce ADRD disparities.