Project Summary The burden of Alzheimer’s Disease and Related Dementias (ADRD) is projected to increase by 150% by the year 2060 to affect 14 million Americans, with four- and seven-fold increases anticipated among Black and Hispanic/Latino older adults. To better understand the accumulation of risk throughout the life course and the disparities that exist in ADRD, studying social and structural determinants of health and employing a life course perspective have been emphasized. Research on the role of early life stressors and adversity on ADRD is emerging, but still limited. Older adults who experienced more childhood adversities had greater likelihood of incident dementia in three international aging cohorts; U.S.-based studies have been largely cross-sectional in design, mixed results have been observed, and only one examined racial/ethnic differences. However, greater understanding of the role these factors play is imperative if we aim to mitigate the risk of ADRD with a health equity lens. Identifying early life risk factors for ADRD and the primary pathways through which childhood adversity is operating will allow for more targeted interventions to reduce risk of ADRD in later life for the most vulnerable in our population. In addition, the role of neighborhood deprivation in these relationships remains understudied, despite known ramifications of environmental factors on health behaviors and outcomes. Understanding structural determinants of health and how they impact risk of ADRD will provide valuable insight for identifying the most vulnerable communities for targeting effective prevention strategies and motive for structural changes and policies that aim to improve these environments and the overall health of those individuals at greatest risk. To have the greatest impact on reducing the risk of ADRD, the role of the environment must be considered. In the F99-phase of this proposed research, Adrienne Lee will conduct three novel studies of these complex associations. Specifically, Adrienne will use the Health and Retirement Study to evaluate the associations of childhood adversity with neighborhood deprivation, cognitive trajectories, and dementia outcomes within racial/ethnic subgroups. She will link the study sample to the area deprivation index in midlife to further understand the role of environment and structural determinants of health on these associations, and to identify population-specific mechanisms by which we can tailor interventions throughout the life course. In the K00-phase of this proposed research, Adrienne will build off her dissertation research to identify early life resilience factors that promote healthy cognitive aging and that may counteract ACE exposure, and she will examine the associations of ACE exposure, in combination with neighborhood deprivation in relation to other hallmarks of aging. This research will inform equitable interventions.