An fMRI Study of Verbal Working Memory in Metabolic Syndrome

描述（由申请人提供）：在美国，随着超重和肥胖的患病率增加，相当一部分老年人患代谢功能障碍的风险越来越大。代谢异常可包括胰岛素抵抗或葡萄糖耐量受损、血脂异常、高血压和腹部肥胖。这些代谢异常往往聚集在一起，形成所谓的代谢综合征（MetSy）。MetSy被广泛认为是与II型糖尿病以及心血管和脑血管疾病的发展相关的“疾病前”状态。几项研究提出了MetSy和神经认知和脑功能障碍的组成部分之间的联系;然而，很少有研究检查了包括综合征的一系列风险因素的累加效应！这项研究的长期目标是发现证据表明，MetSy患者（根据定义，他们没有表现出任何明显的疾病过程）在认知任务上表现出细微的差异和异常的FMRI大脑反应。本研究的具体目的是证明MetSy个体的言语工作记忆（VWM）表现和任务相关BOLD功能磁共振成像脑反应异常的微妙缺陷。假设与匹配良好的对照组相比，具有MetSy的个体：（a）在2-back VWM测试中的反应时间将较不准确和较慢;（B）将表现出2-back表现的差异，其将随着任务难度的增加而增加;（c）在参与VWM的脑系统中具有降低的BOLD反应，包括背外侧前额叶皮层、补充运动区和后顶叶皮层;（d）将在主要VWM系统以外的区域表现出补偿性反应。此外，假设与任务需求相关的大脑反应的增加在MetSy个体中会更高。在美国，24%的成年人和近44%的50岁以上的成年人符合代谢综合征的临床标准。因此，该项目将为数百万患有代谢综合征的美国人提供证据，证明脑血管和认知功能在重大疾病的临床体征存在之前受到细微的血管和非血管异常的影响，从而产生重要的临床应用。

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.