This is an application to renew a K24 Mid-Career Investigator Award in aging-related patient-oriented research. The Awardee is a professor of psychiatry, neurology, and epidemiology with an established track record as a researcher, clinician, and educator. The Awardee's current research focus is on mild cognitive impairment (MCI), a variably defined condition generally regarded as a prodromal and/or risk state for Alzheimer's and other dementias. Her group's epidemiological work , like those of other population-based studies in North America and Europe, has demonstrated that current """"""""diagnostic"""""""" criteria for MCI do not reflect the real-world distribution and outcomes in the typical community or primary care clinical setting, where the majority of older adults are served. In the community at large, MCI is a unstable and heterogeneous entity, particularly in individuals with significant comorbidity. For the concept to be clinically useful, it must have better predictive value for different outcomes. Broadly, the Research Plan aims to refine the current MCI criteria based on predictive validity for dementia, using data from a new, ongoing, representative cohort study that was begun during the current K24 award period. A specific additional proposed activity is to expand the focus on vascular risk factors which are hypothesized to improve prediction of MCI outcomes. Health history and neurological exam, blood pressure, total and HDL cholesterol, and APOE genotype are already being measured on all participants. The proposed new research will obtain measurements on additional peripheral vascular markers (glycosylated hemoglobin, Apo A1, ApoB, homocysteine, C-Reactive Protein, and cystatin) from subgroups of participants with normal cognition and with subtypes of MCI. The renewed K24 will also permit the development of an application for a brain structural MRI project to determine the extent to which global and regional atrophy as well as evidence of cerebrovascular disease improve the predictive value of the clinical data, in a sample of the representative community cohort. The Mentoring Plan remains targeted towards early career investigators in clinical and epidemiological research into cognitive aging and mild cognitive impairment. As appropriate to their backgrounds and goals, trainees will enhance their experience of patient-oriented research;participate in multidisciplinary consensus diagnosis;obtain supervised experience of analyzing, interpreting, and reporting data from the Awardee's ongoing and completed community studies;participate in group interactions around individual research projects;and take advantage of additional educational opportunities available at the institution. Trainees'productivity will be monitored with regard to development of research proposals and publications and maturation as independent investigators. The Awardee will also continue to organize trainee workshops in neglected areas such as project management, principles of neuropsvcholoav for non-psvcholoaists. and scientific writing skills.
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