Project Summary/Abstract There is a fundamental gap in understanding how racial/ethnic differences in blood pressure (BP) control influence ra- cial/ethnic disparities in cognitive impairment and dementia (CID). Poor understanding of the biological factors driving socio-demographic disparities in CID is a critical barrier to the design of interventions aimed to eliminate these dispari- ties. The long-term goal of this research is to develop, test, and disseminate interventions that prevent CID and can be ap- plied to diverse populations. The objectives of this study are to quantify the effects of racial/ethnic differences in BP con- trol on racial/ethnic differences in CID, to quantify the potential impact of optimal BP treatment intensity to reduce ra- cial/ethnic disparities in CID, and to design a feasible BP intervention trial to reduce the risk of CID or cognitive decline. CID is an excellent model of a serious, chronic illness with racial/ethnic disparities in prevalence and costs. High BP is an ideal biological risk factor because it is modifiable with a wide range of effective therapies for management. Our central hypothesis is that racial/ethnic differences in the control of high BP across the life course contribute to racial/ethnic dis- parities in late-life CID. The rationale for the proposed research is that understanding how racial/ethnic differences in BP control from young adulthood to late-life contribute to racial/ethnic disparities in CID has the potential to translate into targeted interventions aimed to improve the quality and outcomes of high BP, resulting in new and innovative approaches to the prevention of CID and other serious, chronic illnesses disproportionately affecting Blacks and Hispanics. Guided by strong preliminary data, this hypothesis will be tested by pursuing 3 specific aims: 1) Determine the influence of lower BP levels from young adulthood to late-life on CID risk in Blacks, Hispanics, and Whites; and 2) Estimate the potential impact of optimal BP treatment intensity to reduce racial/ethnic disparities in CID; and 3) Determine the sample size and duration of a trial that is adequately powered to find an effect size of BP lowering on CID that is clinically im- portant. Under Aim 1, a health services research approach with pooled cohort studies—shown to be feasible in the appli- cants' hands—will be used to measure the effects of BP levels and use of antihypertensive medication from young adult- hood to late-life on CID risk. Under Aims 2 and 3, a simulation modeling approach, which also has been proven as feasi- ble in the applicants' hands, will be used to quantify the individual and societal effects of eliminating racial/ethnic differ- ences in BP control from young adulthood to late-life on racial/ethnic disparities in late-life CID, and to determine the sample size and duration of a BP intervention trial to reduce the risk of CID or cognitive decline in diverse groups. This research proposal is innovative because it includes young adults and Hispanics. Not only do racial/ethnic disparities in BP control begin in young adulthood, but the effect of high BP on cognition also appears to begin in young adulthood. Hispanics are an understudied population that has greater risk of worse BP control and CID than Whites. The study will improve current BP-related risk prediction models by incorporating new population-based risk estimates from diverse co- horts and by adding CID as a BP-related outcome to an existing cardiovascular disease computer simulation model. This CID-enhanced computer simulation model will estimate the individual and societal benefits of optimal BP treatment in- tensity on CID to inform clinical care and policy and determine the sample size and duration of a BP intervention trial to reduce the risk of CID. The proposed study is significant because it will generate new knowledge and methods needed to understand the impact of racial/ethnic differences in optimal BP treatment intensity over the life course on racial/ethnic disparities in CID and to improve the design of BP lowering trials and their application to diverse populations. Ultimately, such knowledge has the potential to inform the development of targeted interventions that will help to improve the pre- vention of CID and to reduce CID-related disability in older Americans particularly minorities.

Narrative The proposed research is relevant to public health because the discovery of the biological mechanisms contributing to racial/ethnic differences in cognitive impairment and dementia is ultimately expected to lead to new vascular interventions that reduce disparities in the cognitive health of Americans. The proposed research is relevant to the part of NIH’s mission of developing fundamental knowledge that will help enhance the health of older adults and reduce the burdens of human disability.