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一个方面，是中风和血管性痴呆的预测因素。在明显的脑血管疾病之前，具有这些心血管（CV）危险因素的人可注意到细微的认知缺陷。然而，将心血管危险因素与较差的认知功能联系起来的生物学机制尚不清楚。在有心血管危险因素的老年人中，认知功能的细微缺陷和伴随的大脑异常可能是脑血管风险升高的早期标志。这个竞争继续项目的第一个具体目的是检查250名无中风、非痴呆和非糖尿病老年人（60-80岁以上），其中90名来自我们最初的R29项目，160名来自这个拟议的项目，心血管危险因素——收缩压和舒张压、血糖、胰岛素、血脂异常和腹部肥胖——是否与较差的结果相关：(1)神经心理测试表现；(2)白质高信号、无症状性梗死和脑萎缩的磁共振成像（MRI）分级；(3)脑大动脉和脑颈动脉狭窄的磁共振血管造影（MRA）评分；(4)单光子发射计算机断层扫描（SPECT）评估脑：小脑灌注的相对比率。第二个具体目的是检查MRI、MRA和SPECT的细微脑异常指数是否介导心血管危险因素与较差的认知功能之间的关系。心血管危险因素和大脑异常的累积负担将与认知功能领域的关系，以及个体危险因素和大脑异常的关系进行检查。据我们所知，这将是第一个研究几个相关的心血管危险因素是否通过几个生物学上合理的大脑机制与健康老年人认知功能下降有关的研究。结构方程模型将用于检查这些变量之间的相互关系模式，并直接测试大脑异常作为心血管危险因素-认知关系的潜在中介。了解与心血管危险因素相关的老年人认知功能障碍的发病机制可能有助于加强预防和干预工作，以降低脑血管风险，保持认知功能，提高生活质量。

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.