Neuroimaging Cognitive Vulnerability in Hypertension

描述（由申请人提供）：认知是功能能力和生活质量最重要的决定因素。认知能力下降会导致严重的心理、社会和经济困难，并对患者从其他医疗问题的治疗中获益的能力产生不利影响。美国成年人认知健康面临的最迅速上升的威胁是肥胖、高血压、高血糖和血脂异常聚集在一个人身上，这种情况被称为代谢综合征（MetS）。令人震惊的是，34-45%的美国成年人目前符合met的标准。虽然我们对每一种被破坏的外围生理机制都有一些了解，但我们对将这种综合征与大脑健康和认知联系起来的核心机制知之甚少。这项工作的目的是在临床显著和永久性认知功能障碍发展之前，探索中年与met相关的大脑易感性的潜在神经机制。了解疾病的临床前阶段具有巨大的优势，可以为早期干预提供机会，这比在生命后期努力恢复失去的功能有更高的成功前景。该项目的具体目标将通过在组间横断面设计中检查认知功能完整的中年人（有和没有MetS）的行为表现、脑代谢和大脑对认知挑战的反应来完成。我们建议首先使用功能磁共振成像（fMRI）定义与MetS相关的认知脑血管反应的独特模式；然后，利用神经光谱学（1H MRS）表征与中年MetS相关的神经元活力变化；最后，为了测试神经化学变化是否介导了观察到的大脑功能激活的变化，以应对认知挑战，使用路径分析。

DESCRIPTION (provided by applicant): 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.