The overarching goal of the current proposal is to develop a programmatic line of research that investigates obesity's impact on cognition and cerebral health. Obesity is an established risk factor for dementia and cerebral atrophy in older age. However, little is known about the early signs of these deleterious brain effects or the physiological mechanisms that underlie them. The proposed research will incorporate functional magnetic resonance imaging (fMRI) to define the unique patterns of functional brain response associated with increased central adiposity in cognitively normal middle-aged and older adults. Based on previous neuroimaging studies on cognitively-vulnerable populations, it is hypothesized that increased central adiposity will be associated with lower activation in task-related areas. In order to determine if the adiposity- related alterations are specific to cognitio as opposed to global changes in cerebrovascular reactivity, the response to working memory will be compared to those during hypercapnia, a non-cognitive challenge associated with a robust change in the BOLD response. As a secondary aim, magnetic resonance spectroscopy (1H MRS) will be employed to provide information about neuronal integrity and viability, shedding insight on pathogenic mechanisms. It is hypothesized that reduced neuronal viability, as assessed by N- acetyl-asparate (NAA), will mediate the association between central adiposity and functional brain response to cognition. Findings are expected to fill crucial gaps in the current understanding of the impact of obesity, a pervasive condition, on cognitive outcomes. Moreover, this project will provide a framework for the applicant to develop specific training in methods and analysis techniques required to meet future career goals. This training includes (a) experience conducting research with human subjects;(b) neuropsychological assessment;(c) design and analysis of an fMRI study;(d) advanced statistical techniques for fMRI and 1H MRS data;and (e) cross-disciplinary training in human and exercise physiology in service of the long-term goal to design and implement interventions for preserving cognitive function by preventing the deleterious effects of obesity on the brain.
Obesity has been identified as an important risk factor for dementia and brain volume loss in old age. Given that almost two-thirds of American adults are either overweight or obese, a better understanding of the extent to and the mechanisms by which obesity affects the brain is crucial for ensuring optimal health across the lifespan. The current proposal outlines a study that utilizes magnetic resonance imaging in order to examine obesity's impact on the brain in middle- aged and older adults with the ultimate aim of developing interventions to prevent cognitive decline.
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