This application seeks to continue the Chicago Health and Aging Project (CHAP), which collects data from a biracial (non-Hispanic black and non-Hispanic white) cohort of residents, age 65 and older, of a geographically defined community of the south side of Chicago. The application proposes testing hypotheses in two major areas. In the first, we will focus on the full continuum of cognitive decline in older age from very mild to very severe. We propose to evaluate two complementary approaches to studying this continuum, as distinct clinical syndromes, i. e., No Cognitive Impairment (NCI), Mild Cognitive Impairment (MCI), and dementia /Alzheimer's disease (AD) vs. direct longitudinal measurement of continuously distributed change in cognitive function. We hypothesize that direct measurement of change in cognitive function will offer greater power with reduced bias. We will emphasize evaluation of vascular risk factors and examination of racial/ethnic variation in risk. Second, we will examine the relations of three markers of inflammation, Interleukin-6 (IL-6), C-Reactive Protein (CRP), and Tumor Necrosis Factor-a (TNF-a) to these outcomes. We hypothesize that each marker will be associated , both cross-sectionally and longitudinally, with change in cognitive function, MCI, and AD, that these associations will be stronger for white than for black subjects, and that associations with blood pressure and other vascular risk factors will be stronger among subjects with higher levels of IL-6, CRP, and TNF-a. We further propose to complete collection of specimens of DNA and serum for the population sample and plasma for a random sample of 1000 subjects so as to facilitate further studies of genetics and biomarkers in relation to cognitive decline, MCI, and Alzheimer's disease.
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