Epidemiology of Glycemia Inflammation & Cognition

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This application is for a KOI Mentored Research Scientist Development Award through which the candidate will learn how type 2 diabetes, glucose disorders, arid inflammation contribute to cognitive decline and dementia. The overall goal of this proposal will be to determine whether levels of glycemia and insulinemia are predictive of cognitive decline across the entire range of glucose tolerance and across different ethnic groups. Furthermore, whether differences in inflammation explain predictive associations between glycemia and cognitive performance will be examined. Within the research plan, this goal will be achieved though conducting three prospective studies. The following are the specific aims: 1). To determine the association of measures of glycemia and insulinemia with cognitive functioning. 2). To determine if the association of type 2 diabetes, markers of glycemia and insulinemia, with cognition is mediated by levels of inflammation including c reactive protein, tumor necrosis factor alpha-1, interleukin-6, and plasminogen activator-1. 3). To determine how longitudinal changes in glycemia and insulinemia are associated with cognitive impairment. 4). To determine how glycated hemoglobin is associated with risk of incident dementia, Alzheimer's disease and vascular dementia in patients with Type 2 diabetes. A multidisciplinary team of established senior investigators, each with a different area of expertise and training including diabetes, neurology and epidemiology, has been formed to mentor the candidate on the research and career development plan proposed. The training component of the career plan includes the skills gleaned from the research plan as well as an impressive array of structured activities including formal coursework in diabetes, inflammation and endocrinology, participation in several seminar series on diabetes and dementia, additional collaborations with a biostatistician and geriatrician, regular mentoring interactions; and attendance/presentation at several scientific meetings. The candidate has proposed three studies which seek to gain new knowledge about glycemic and inflammatory risk factors for cognitive impairment in multiethnic cohorts. The expected results should provide new and clinically useful information regarding the influences of glycemic control and glucose disorders on neurocognitive functioning. The proposed KOI application includes an excellent research environment including resources specific to the goals of the training plan, an established team of mentors and, an important research question. The support from the Mentored Scientist Career Award will enable the candidate to make the transition to an independent investigator in the area of glycemia and cognition including establishing an extramurally funded research program.