Healthy Heart, Healthy Brain? A Pooled Life-course Cohort for Dementia Risk Assessment

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ABSTRACT Neurodegenerative processes leading to dementia, especially Alzheimer disease, begin long before clinical features become apparent, and several lines of evidence suggest that cardiovascular risk factor reduction may be one of the most viable strategies to modify the course of the preclinical phase. Exposure to cardiovascular risk factors begins early in life and continues throughout adulthood with pronounced gender and racial/ethnic differences in the age at which cardiovascular exposures develop. For example, Blacks may show earlier, longer and more severe exposure to cardiovascular risk than whites. However, current evidence about the timing and influence of these exposures on cognitive aging and Alzheimer disease is controversial, supporting the need for a life-course approach. For example, the effects of hypertension may be more adverse in mid-life than late-life. Furthermore, there is growing consensus that racial/ethnic and gender disparities in risk of Alzheimer disease and cognitive function may exist. These disparities may partly stem from differences in prevalence and cumulative cardiovascular risks, as well as differences in their association with Alzheimer disease and cognition. Yet, there is a paucity of longitudinal research addressing these associations within a life-course framework. This study will use published statistical methods in a novel way to pool multiple data and to create a pooled cohort in order to provide improved estimates of age-specific exposures to cardiovascular risk factors over the life-course on Alzheimer disease and cognitive outcomes associated with aging. We will work with four biracial prospective cohorts which together span the adult life-course, and with compatible data on major cardiovascular risk factors, mid and late life cognition and dementia outcomes: the Coronary Artery Risk Development in Young Adults (CARDIA), Multi Ethnic Study of Atherosclerosis (MESA), Cardiovascular Health Study (CHS), and Health, Aging and Body Composition Study (Health ABC). This poled cohort will enable us to 1) estimate life-course exposures to cardiovascular risk factors, in particular for participants with follow-up starting later in life, then 2) determine the type and timing of exposures that influence cognitive decline and risk of Alzheimer disease and other dementia, and 3) how modifications of these exposures may reduce the burden of cognitive decline and Alzheimer disease, as well as racial and gender disparities. Understanding how modifications of these exposures may reduce the burden of cognitive decline and Alzheimer disease is critical for public health.