Neuroimaging Cognitive Vulnerability in Hypertension

描述(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。认知能力下降可能会导致严重的心理、社会和经济困难，并对一个人从其他医疗问题的治疗中受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、高血糖和血脂异常在一个人身上聚集，这种情况被称为代谢综合征(METS)。目前，高达34%-45%的美国成年人符合大都会大学入学考试的标准。虽然我们对每一种被破坏的外周生理机制都有一些信息，但对将综合症与大脑健康和认知联系起来的中央机制知之甚少。这项拟议工作的目标是在临床上有意义的永久性认知功能障碍形成之前，探索中年期间甲硫氨酸相关脑脆弱性的潜在神经机制。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，这项任务比努力在以后的生活中恢复失去的功能更有希望取得成功。该项目的具体目标将通过在小组间横断面设计中检查认知正常的中年成年人在接受和不接受MET的情况下的行为表现、大脑新陈代谢和大脑反应来实现。我们建议首先使用功能磁共振成像(FMRI)定义与METS相关的认知的脑血管反应的独特模式；然后使用神经波谱(1HMRS)表征与中年METS相关的神经元活性的变化；最后，使用通径分析来测试神经化学变化是否中介了所观察到的大脑功能激活的变化，以响应认知挑战。 公共卫生相关性：认知是功能能力和生活质量的最重要决定因素。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、高血糖和血脂异常在一个人身上聚集，这种情况被称为代谢综合征(METS)，但人们对这种综合征与大脑健康之间的联系机制知之甚少。这项拟议工作的目标是探索中年蛋氨酸相关脑脆弱性的潜在神经机制，以指导预防和治疗晚年认知障碍的努力，并确保我们日益增长的老年人口成功老龄化。

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. 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.