Hypertension, Cognition, and the Brain in Older Adults

描述(申请人提供)：高血压、血脂异常、高胰岛素血症、糖耐量低减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子。在显性脑血管疾病之前，具有这些心血管(CV)危险因素的人会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却知之甚少。认知功能的细微缺陷和伴随的脑异常可能构成有心血管危险因素的老年人脑血管风险升高的早期标志。这个竞争性的延续项目的第一个具体目标是检查250名无中风、非痴呆和非糖尿病的老年人(60-80岁)，其中90人来自我们最初的R29项目，160人来自这个拟议项目，心血管危险因素-收缩和舒张压、血糖、胰岛素、血脂异常和腹部肥胖-是否与较差的预后相关：(1)神经心理测试表现；(2)脑白质高信号、静止性脑梗塞和脑萎缩的磁共振成像(MRI)评级；(3)大脑大动脉和颈动脉狭窄的磁共振血管成像(MRA)评级；(4)单光子发射计算机断层扫描(SPECT)评价脑/小脑血流灌注的相对比值。第二个具体目的是检查MRI、MRA和SPECT指数是否在脑血管疾病危险因素与认知功能较差之间的关系中起中介作用。与认知功能领域相关的CV风险因素和脑异常的累积负担将被检查，以及个人风险因素和脑异常。据我们所知，这将是第一次研究几个相互关联的CV风险因素是否通过几种生物学上看似合理的大脑机制与其他健康的老年人的认知功能减弱有关。结构方程模型将被用来检验这些变量之间的相互关系模式，并直接测试大脑异常作为CV风险因素-认知关系的潜在中介。了解老年人与心血管危险因素相关的认知损害的发病机制，可能有助于加强预防和干预工作，以降低脑血管风险，保护认知功能，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.