An fMRI Study of Verbal Working Memory in Metabolic Syndrome

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DESCRIPTION (provided by applicant): Concurrent with the increased prevalence of overweight and obesity in the United States, a significant portion of older adults are increasingly at risk for developing metabolic dysfunction. Metabolic abnormalities can include insulin resistance or impaired glucose tolerance, dyslipidemia, hypertension, and abdominal obesity. These metabolic abnormalities tend to cluster together, forming what is known as metabolic syndrome (MetSy). MetSy is widely considered a "pre-disease" state associated with development of Type II Diabetes as well as cardiovascular and cerebrovascular disease. Several studies have proposed links between components of MetSy and neurocognitive and brain dysfunction; however, few studies have examined the additive effect of the cluster of risk factors that comprise the syndrome! The long-term objective of this study is to uncover evidence that individuals with MetSy, who by definition do not exhibit any overt disease process, will demonstrate subtle differences in performance and abnormal FMRI brain response on cognitive tasks. The specific aims of the study are to demonstrate subtle deficits in verbal working memory (VWM) performance and abnormalities in task-related BOLD FMRI brain response in individuals with MetSy. It is hypothesized that in comparison to a well-matched control group, individuals with MetSy: (a) will be less accurate and slower in their reaction times on the 2-back VWM test; (b) will exhibit differences in 2-back performance that will increase in relation to increased task difficulty; (c) will have reduced BOLD response in brain systems involved in VWM including the dorsolateral prefrontal cortex, supplemental motor area, and the posterior parietal cortex; (d) will exhibit compensatory responses in areas outside the primary VWM system. Additionally, it is hypothesized that increases in brain response in relation to task demand will be higher in individuals with MetSy. Relevance to Public Health In the United States, 24% of adults and nearly 44% of adults over the age of 50 years meet the clinical criteria for metabolic syndrome. Thus, this project will yield significant clinical application for millions of Americans with metabolic syndrome by providing evidence that cerebrovascular and cognitive function are affected by subtle vascular and non-vascular abnormalities before clinical signs of major disease exist.