The primary objective of this Career Development Award application is to enable the applicant to develop the skills and expertise necessary to become an expert in the epidemiologic study of cognitive decline in the elderly, with an emphasis on the potential protective effects of physical activity. There is compelling evidence from both animal and human studies that physical activity may lower the risk of cognitive decline and dementia, although several key issues remain unresolved. The proposed Training Plan will provide the applicant with the tools necessary to address these issues and will include coursework and focused mentoring in the areas of metaanalysis, longitudinal data analysis, randomized controlled trial design, measurement of physical activity in the elderly, diagnosis and pathophysiology of dementia, and ethical conduct of research. The proposed Research Plan will utilize the techniques learned to address several key questions about the association between physical activity and cognitive decline. Specifically, we will: 1) determine the strength and consistency of the association based on a meta-analysis of longitudinal, observational studies (Aim 1); 2) conduct a series of studies in participants in the Cardiovascular Health Study, which is a 12-year, longitudinal study of 5,888 white and African American adults age 65 years or older, to determine a) the amounts and types of physical activity associated with the lowest risks of cognitive decline, b) whether the association differs by gender or ethnicity, c) the timing of the association (i.e., chicken vs. egg), and d) whether the association is mediated by vascular disease, inflammation or structural brain changes on magnetic resonance imaging (Aims 2 and 3); and 3) conduct a pilot study to evaluate the feasibility of a randomized controlled trial in elders at risk of cognitive decline (Aim 4). This combination of training and research will enable the applicant to develop the skills necessary to transition successfully to independence and also will substantially advance the field on physical ? activity and cognitive decline. ? ?
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