ABSTRACT U.S. veterans are an increasingly racially, ethnically, and geographically diverse group that has a high risk of Alzheimer's Disease and Related Dementias (ADRD) due to their high prevalence of cardiovascular risk factors including hypertension and heightened exposure to ADRD risk factors such as traumatic brain injury (TBI), posttraumatic stress disorder (PTSD), and depression (hereafter, military-related exposures). Although veterans are understudied in ADRD research, these characteristics make this high-risk population well-suited to improve understanding of psychosocial and vascular drivers of ADRD risk and disparities. In particular, several lines of evidence suggest that hypertension is a major dementia risk factor and that antihypertensive treatment may be a promising strategy for ADRD risk reduction and prevention. Yet, hypertension, its treatment and target goals, and association with dementia risk all vary by race/ethnicity, geography, and other risk factors, necessitating the use of large and diverse cohorts to robustly examine these associations within important potentially high-risk subgroups. The Veterans Health Administration (VHA) provides health care to veterans that in turn is captured in electronic health records (EHR) stored in a national repository. This rich dataset will enable investigation of hypertension and ADRD risk, including within subgroups defined by military-related exposures, race/ethnic groups, and US region. Further, because the VHA is a single-payer healthcare system, we expect treatment guidelines to be relatively standard across providers, enabling the use of contemporary econometric methods, such as regression discontinuity designs (RDD), to estimate causal effects of hypertension treatment with different treatment cutoffs for optimized ADRD risk reduction. Using a sample of 1,415,230 older veterans (mean age: 66 years; 149,436 from under-represented minority groups; 32,551 women and 1,122,016 with hypertension), we propose to estimate the association between hypertension and ADRD risk among US veterans and within race/ethnicity and geographical region subgroups (Aim 1) and then assess if military-related exposures (e.g., TBI, PTSD, depression) modify this association, overall and within subgroups (Aim 2). We will then estimate hypertension treatment effects on ADRD risk using a regression discontinuity design and different treatment targets and assess if this varies by subgroup and military-related exposures (Aim 3a). Finally, we will quantify the reduction in ADRD cases that could be achieved at different treatment targets (Aim 3b). This innovative study will provide multiple public health relevant estimates for the relationship of hypertension, treatment targets, and ADRD risk. By also examining these associations within subgroups of race/ethnicity, region, and presence of military-related exposures, this study will enable identification and prioritization of groups at highest risk of ADRD. As we...