15. Project Summary/Abstract: The prevalence of Alzheimer's disease (AD) is closely related to the presence of cardiovascular disease (CaVD), understanding the relationship between amyloid-beta (A?) pathology and CaVD is critically important. The overarching goal of this study is to further the understanding of the relationship between AD pathology, including A? and tau pathology and neurodegeneration, cerebrovascular reactivity and midlife CaVD. To achieve these goals, we will utilize a group non-demented participants from an existing cohort from the ongoing community-based Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) study, a longitudinal study that began in 2003 with a cohort of 2000 participants (43% black) between the ages of 45-75 years at study entry and has collected a wealth of longitudinal vascular measures. We hypothesize that subclinical CaVD identified in midlife is associated with increased risk for Alzheimer's disease pathology expressed as amyloid deposition and neurodegeneration. These changes in brain structure would be associated with alterations in cognition both cross-sectionally and longitudinally. We further hypothesize that the change in cognition will result from a failure of vascular compensatory responses, marked by increases in regional cerebral blood flow and cerebrovascular reactivity.