An fMRI Study of Verbal Working Memory in Metabolic Syndrome

描述（由申请人提供）：随着美国超重和肥胖患病率的增加，相当一部分老年人发生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被广泛认为是一种与II型糖尿病和心脑血管疾病发展相关的“疾病前”状态。一些研究已经提出了MetSy成分与神经认知和脑功能障碍之间的联系；然而，很少有研究检查了构成该综合征的一系列风险因素的叠加效应！这项研究的长期目标是揭示MetSy患者的证据，根据定义，他们没有表现出任何明显的疾病过程，在认知任务的表现和异常的FMRI脑反应方面会表现出微妙的差异。本研究的具体目的是证明MetSy患者言语工作记忆（VWM）表现的细微缺陷和任务相关的BOLD FMRI脑反应的异常。假设与匹配良好的对照组相比，MetSy个体：(a)在2-back VWM测试中的反应时间准确性较低，反应速度较慢；(b)会表现出与任务难度增加相关的双背表现差异；(c)与VWM有关的脑系统，包括背外侧前额叶皮层、辅助运动区和后顶叶皮层的BOLD反应会减少；(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MetSy患者的大脑反应与任务需求相关的增加会更高。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出现重大疾病的临床症状之前就受到了细微的血管和非血管异常的影响，从而具有重要的临床应用价值。

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.