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.

Public Health Relevance

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.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Predoctoral Individual National Research Service Award (F31)
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Special Emphasis Panel (ZRG1-F02A-J (20))
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Wagster, Molly V
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University of Texas Austin
Schools of Arts and Sciences
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Kaur, Sonya; Gonzales, Mitzi M; Tarumi, Takashi et al. (2016) Serum Brain-Derived Neurotrophic Factor Mediates the Relationship between Abdominal Adiposity and Executive Function in Middle Age. J Int Neuropsychol Soc 22:493-500
Kaur, Sonya; Gonzales, Mitzi M; Strasser, Barbara et al. (2015) Central Adiposity and Cortical Thickness in Midlife. Psychosom Med 77:671-8
Pasha, Evan P; Kaur, Sonya S; Gonzales, Mitzi M et al. (2015) Vascular function, cerebral cortical thickness, and cognitive performance in middle-aged Hispanic and non-Hispanic Caucasian adults. J Clin Hypertens (Greenwich) 17:306-12
Tarumi, Takashi; Gonzales, Mitzi M; Fallow, Bennett et al. (2015) Cerebral/Peripheral Vascular Reactivity and Neurocognition in Middle-Age Athletes. Med Sci Sports Exerc 47:2595-603
Strasser, B; Arvandi, M; Pasha, E P et al. (2015) Abdominal obesity is associated with arterial stiffness in middle-aged adults. Nutr Metab Cardiovasc Dis 25:495-502
Kaur, Sonya S; Gonzales, Mitzi M; Eagan, Danielle E et al. (2015) Inflammation as a mediator of the relationship between cortical thickness and metabolic syndrome. Brain Imaging Behav 9:737-43
Gonzales, Mitzi M; Tarumi, Takashi; Mumford, Jeanette A et al. (2014) Greater BOLD response to working memory in endurance-trained adults revealed by breath-hold calibration. Hum Brain Mapp 35:2898-910
Gonzales, M M; Kaur, S; Eagan, D E et al. (2014) Central adiposity and the functional magnetic resonance imaging response to cognitive challenge. Int J Obes (Lond) 38:1193-9
Tarumi, Takashi; Gonzales, Mitzi M; Fallow, Bennett et al. (2013) Central artery stiffness, neuropsychological function, and cerebral perfusion in sedentary and endurance-trained middle-aged adults. J Hypertens 31:2400-9
Tarumi, Takashi; Gonzales, Mitzi M; Fallow, Bennett et al. (2013) Aerobic fitness and cognitive function in midlife: an association mediated by plasma insulin. Metab Brain Dis 28:727-30

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