This is a revision of a previous application that was not funded. It proposes to continue the Chicago Health and Aging Project (CHAP), a study of incident clinically diagnosed Alzheimer's Disease among 6,162 residents of a geographically defined, urban, biracial community of the south side of Chicago. Recent data from the studies suggest that prevalence of Alzheimer's Disease is 2.65-fold higher among blacks than whites after adjustment for age, education and APOE genotype. The proposed work examines potentially modifiable risk factors, especially ones that might explain racial differences in risk. The primary questions are: (1) whether vascular factors, especially elevated blood pressure, increase risk of clinically manifest Alzheimer's Disease itself, in addition to their accepted role in predicting risk of vascular dementia, (2) whether this is mediated through small brain infarcts and non-infarct related white matter changes, and (3) to what extent do vascular factors account for racial differences in risk of disease? Secondary issues include potential protective effects of anti-inflammatory drugs and estrogens, effects of early life exposure on risk of Alzheimer's Disease, and the extent to which vascular factors predict risk of vascular dementia. To achieve these goals, a proposed second follow up (incidence) data collection cycle will detect Alzheimer's Disease occurring in the three year interval since the previous cycle, and all clinical evaluations will include magnetic resonance imaging and magnetic resonance and geography. In addition, enrollment of successive age cohorts of community residents as they reach age 65 is proposed to enable the study, in the future, to examine three important issues that cannot be examined by existing studies: whether effects of risk factors for Alzheimer's Disease vary greatly with age, the need for exposure information at multiple points over an extended period of time, and differences in the occurrence and effects of risk factors in different age cohorts.
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