Hypertension, Cognition, and the Brain in Older Adults

描述（由申请人提供）：高血压、血脂异常、高胰岛素血症、葡萄糖耐受不良和腹部肥胖是代谢综合征的多个方面，是卒中和血管性痴呆的预测因子。在明显的脑血管疾病之前，在具有这些心血管（CV）风险因素的人中注意到微妙的认知缺陷。然而，将CV风险因素与认知功能较差联系起来的生物学机制知之甚少。认知功能的轻微缺陷和伴随的大脑异常可能构成具有CV风险因素的老年人中脑血管风险升高的早期标志物。这个竞争性的延续项目的第一个具体目标是研究在250名无中风、非痴呆和非糖尿病的老年人中，（年龄60-80岁以上），90例来自我们最初的R29项目，160例来自本拟议项目，CV风险因素-收缩压和舒张压、血糖、胰岛素、血脂异常，和腹部肥胖-与以下方面的不良结果相关：（1）神经心理学测试表现;（2）磁共振成像（MRI）对白色高信号、无症状性梗死和脑萎缩的评级;（3）大脑和颈脑大动脉狭窄的磁共振血管造影（MRA）评级;和（4）通过单光子发射计算机断层扫描（SPECT）评估的大脑：小脑灌注的相对比率。第二个具体目标是检查轻微脑异常的MRI、MRA和SPECT指数是否介导CV风险因素与认知功能较差之间的关系。将检查与认知功能领域相关的CV风险因素和脑异常的累积负担，以及个体风险因素和脑异常。据我们所知，这将是第一项研究，以检查几个相互关联的CV风险因素是否与认知功能下降通过几个生物学上合理的大脑机制，在其他健康的老年人。将使用结构方程模型来检查这些变量之间的相互关系模式，并直接检测脑异常作为CV风险因素-认知关系的潜在介质。了解老年人中与CV风险因素相关的认知功能障碍的发病机制，可能会加强预防和干预工作，以降低脑血管风险，保护认知功能并改善生活质量。

DESCRIPTION (provided by applicant): Hypertension, dyslipidemia, hyperinsulinemia, glucose intolerance, and abdominal adiposity are facets of the metabolic syndrome, and are predictors of stroke and vascular dementia. Prior to overt cerebrovascular disease, subtle cognitive deficits are noted in persons with these cardiovascular (CV) risk factors. However, the biological mechanisms linking CV risk factors to poorer cognitive function are poorly understood. Subtle deficits in cognitive function and accompanying brain abnormalities may constitute early markers of elevated cerebrovascular risk among older adults with CV risk factors. The first specific aim of this competing continuation project is to examine whether, in 250 stroke-free, non-demented and non-diabetic older adults (ages 60-80+), 90 from our initial R29 project combined with 160 from this proposed project, CV risk factors - systolic and diastolic blood pressure, blood glucose, insulin, dyslipidemia, and abdominal adiposity - are associated with the poorer outcomes on: (1) neuropsychological test performance; (2) magnetic resonance imaging (MRI) ratings of white matter hyperintensities, silent infarction, and brain atrophy; (3) magnetic resonance angiography (MRA) ratings of stenosis of the large cerebral and cervicocerebral arteries; and (4) relative ratios of cerebral:cerebellar perfusion as assessed by single photon emission computed tomography (SPECT). The second specific aim is to examine whether MRI, MRA, and SPECT indices of subtle brain abnormalities mediate the relation between CV risk factors and poorer cognitive function. The cumulative burden of the CV risk factors and brain abnormalities will be examined in relation to domains of cognitive function, as will individual risk factors and brain abnormalities. To our knowledge, this will be the first study to examine whether several interrelated CV risk factors are associated with diminished cognitive function via several biologically plausible brain mechanisms in otherwise healthy older adults. Structural equation modeling will be used to examine patterns of interrelations among these variables and directly test brain abnormalities as potential mediators of the CV risk factor-cognition relation. Understanding the pathogenesis of cognitive impairment associated with CV risk factors in older adults may lead to enhanced efforts in prevention and intervention to reduce cerebrovascular risk, preserve cognitive functioning, and improve quality of life.