Cognition is the most important determinant of functional ability and quality of life. Diminished cognitive capacity can cause significant psychological, social, and economic hardship and adversely impact a person's ability to benefit from treatment for other medical problems. The most rapidly rising threat to cognitive health in US adults is the clustering of obesity, hypertension, hyperglycemia and dyslipidemia in a single person, a condition known as metabolic syndrome (MetS). A staggering 34-45% of US adults currently fulfill criteria for MetS. While we have some information about each of the disrupted peripheral physiological mechanisms in turn, very little is known about the central mechanisms that connect the syndrome to brain health and cognition. The goal of the proposed work is to explore the underlying neural mechanisms of MetS-related brain vulnerability in midlife, before clinically significant and permanent cognitive dysfunction has developed. Understanding the pre-clinical stages of disease has the enormous advantage of presenting opportunities for early intervention, a task with much higher prospect of success than striving to restore lost function later in life.
The specific aims of this project will be accomplished by examining behavioral performance, cerebral metabolism, and brain response to a cognitive challenge in cognitively intact middle-aged adults with and without MetS in a cross sectional between groups design. We propose to first define the unique patterns of cerebrovascular response to cognition associated with MetS using functional magnetic resonance imaging (fMRI);then, to characterize the changes in neuronal viability associated with midlife MetS using neurospectroscopy (1H MRS);and finally, to test if neurochemical alterations mediate the observed alterations in functional brain activation in response to a cognitive challenge using path analysis.

Public Health Relevance

Cognition is the most important determinant of functional ability and quality of life. The most rapidly rising threat to cognitive health in US adults is the clustering of obesity, hypertension, hyperglycemia and dyslipidemia in a single person, a condition known as metabolic syndrome (MetS), yet little is known about the mechanisms that connect the syndrome to brain health. The goal of the proposed work is to explore the underlying neural mechanisms of MetS-related brain vulnerability in midlife, in order to guide efforts to prevent and treat late-life cognitive impairment, and ensure successful aging for our growing population of elderly.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS075565-03
Application #
8533041
Study Section
Aging Systems and Geriatrics Study Section (ASG)
Program Officer
Babcock, Debra J
Project Start
2011-09-01
Project End
2014-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
3
Fiscal Year
2013
Total Cost
$320,745
Indirect Cost
$109,651
Name
University of Texas Austin
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
170230239
City
Austin
State
TX
Country
United States
Zip Code
78712
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
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
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
Haley, Andreana P; Alosco, Michael L; Gunstad, John (2015) Surgical and Nonsurgical Interventions for Obesity in Service of Preserving Cognitive Function. Psychosom Med 77:679-87
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
Kaur, Sonya; Gonzales, Mitzi M; Strasser, Barbara et al. (2015) Central Adiposity and Cortical Thickness in Midlife. Psychosom Med 77:671-8
Laosiripisan, Jitanan; Tarumi, Takashi; Gonzales, Mitzi M et al. (2015) Association between cardiovagal baroreflex sensitivity and baseline cerebral perfusion of the hippocampus. Clin Auton Res 25:213-8
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
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
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

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