This application for a Mentored Patient-Oriented Research Career Development Award (K23) is designed to provide the candidate with advanced skills needed to establish an independent program of research in the cognitive neuroscience of aging and dementia risk. The candidate proposes a five-year comprehensive training plan that combines advanced skill training, didactics, and formal instruction with a team of mentors and advisors. Specific training goals include expanding established skill sets and in developing expertise in the following areas: 1) novel structural neuroimaging methodologies, 2) theoretical and applied aspects of cognitive neuroscience research, specifically as they relate to cognitive aging and dementia risk, and 3) the integration of these methodologies to better understand the relationship between brain structure and function in the context of specific risk factors for dementia. The Mentorship team, which includes individuals with expertise in cognitive neuropsychology, neuroimaging, experimental psychology, cognitive aging, dementia and epidemiology, coupled with the training environments of Brigham and Women's Hospital, the VA Boston Healthcare System, and the Athinoula A. Martinos Center for Biomedical Imaging will ensure superb instruction in these three areas. The proposed research project will integrate advanced methods of morphological measurement of gray matter, novel diffusion tensor imaging (DTI) measures of white matter (WM) microstructure, and neuropsychological testing to better understand the impact of dementia risk factors on structure and function. The project has three specific aims, including: 1) determining the association among the integrity of underlying gray matter, cognition, and risk factors for AD and CVD, 2) determining the association among the integrity of WM microstructure, cognition, and risk factors, and 3) examining these relationships longitudinally. These data will further elucidate the neuroanatomical and neuropsychological characteristics associated with risk factors and will provide unique information regarding structure-function relationships that may exist long before a clinical disease process begins. Collectively, the career training and research components described in this application will allow the candidate to emerge as an independent investigator conducting neuroanatomical and neuropsychological studies of aging and risk for cognitive decline.
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