This is an application for a Mentored Patient-Oriented Research Development Award (K23). The goal of the proposed project is to provide the Applicant with advanced skills needed to establish an independent program of research in cognitive aging using neuroimaging and epidemiological methodologies. The Applicant proposes a comprehensive training plan, combining didactic instruction with established researchers; formal coursework; participation in ongoing seminars at Columbia University; and applied training experiences with individual advisors. Specific training goals include advanced knowledge and skill acquisition in the neurobiological mechanisms of cognitive aging; potential mediators and moderators of cognitive aging, including cerebrovascular risk factors and cross-cultural issues; design, implementation, and statistical analysis of epidemiological studies; principles of magnetic resonance imaging (MRI) and advanced neuromorphometric analysis; and the responsible conduct of research. The training plan will be executed in coordination with a proposed study that utilizes data from the Washington Heights Inwood Columbia Aging Project (WHICAP), an ongoing NIA funded study (P01AG007232) of risk factors for dementia in a multiethnic population of older adults residing in northern Manhattan. Although the main goal of WHICAP is to elucidate risk factors of Alzheimer's disease, it does not explicitly characterize neuromorphology or cognition in individuals who do not develop dementia. The proposed study will address the determinants of neuromorphology and related cognitive profiles among approximately 700 older individuals in the WHICAP cohort with """"""""normal"""""""" age-related cognitive function. The project will examine the association between chronological age and several measures of neuromorphology, including regional volumes, white matter hyperintensity burden, and a new multivariate approach for the characterization of age-associated patterns of gray and white matter. These measures will be related to baseline performance on neuropsychological tests and change in cognition following an 18-month period. A secondary goal will be to examine the mediating effect of cerebrovascular risk factors (i.e., hypertension, insulin resistance, obesity, and hypercholesterolemia) and ethnic group differences on neuromorphology. The proposed project aims will therefore elucidate neurobiological changes ? ? associated with aging and will serve as a bridge for the Applicant to establish an independent investigator career in conducting large- scale neuromorphometry studies on clinical populations. ? ? ?
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