This application for a Mentored Patient-Oriented Research Career Development Award (K23) is intended to provide specific skills and mentorship to the candidate in complementary and integrative areas of cognitive neuroscience in preparation for an independent research career. This proposal describes a comprehensive five- year training plan focused on expanding the candidate's skills and developing expertise in the following three areas: (1) theoretical and applied aspects of the neuropsychology of aging and dementia risk, (2) structural imaging methodologies with an emphasis on diffusion tensor imaging (DTI), and (3) the integration of these two areas with an experimental learning paradigm, eyeblink classical conditioning (EBCC), to better understand the nature of brain structure-function relationships. The focus of this proposal and training plan lies in the strength of each approach and the synergy gained through their integration. This will be accomplished with advanced training, mentorship, didactics, and formal instruction in these content areas in an enriched training environment with a team of skilled and dedicated mentors, consultants, and advisors. The training environments will provide excellent institutional support and tremendous resources to the candidate. The mentors, advisors, and consultants include experts in each facet of proposed training and research areas and will ensure exemplary guidance. The proposed research project will use the eyeblink classical conditioning paradigm and neuropsychological assessment to link behavioral changes to underlying neuropathological changes in a population of aging individuals at risk for Alzheimer's disease (AD) and cerebrovascular disease (CVD). AD and CVD adversely impact the brain in different regions and are characterized by distinct neuroanatomical and neuropsychological underpinnings. These brain regions have been implicated in the circuit underlying the acquisition and expression of EBCC associative responses. This proposal has three specific aims: (1) to determine if performance in a complex EBCC learning task can dissociate individuals at risk AD from CVD, (2) to determine if these learning impairments will be associated with dissociable morphometric changes, and (3) to examine the rates of decline longitudinally.
Evidence suggests that cognitive disorders that are increasingly prevalent with age have their beginnings in physiological, anatomical, and cognitive alterations that are in place years before a clinical entity is detected. This project will determine if EBCC can detect behavioral changes in individuals at risk for dementia before those diseases develop, and provide unique information on brain structure-function relationships.
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