Cerebrovascular Disease and its Consequences in the Strong Study Cohort

描述(申请人提供)：脑血管疾病(CBVD)是导致发病率和死亡率的主要原因，与认知和运动障碍以及抑郁症有关。磁共振成像(MRI)重新定义了大型队列研究中的CBVD，如心血管健康研究(CHS)和社区动脉粥样硬化风险(ARIC)。在CHS和ARIC中，MRI显示在没有已知的中风或短暂性脑缺血发作的人群中，脑部异常的发生率很高，特别是脑白质高信号、梗塞和出血。此外，显性的CBVD，如中风，明显低于隐蔽的MRI定义的脑部疾病。然而，这些隐蔽的发现并不是衰老的良性伴随，因为它们与运动功能和认知受损、抑郁以及随后中风和死亡风险的显著增加有关。这些研究令人信服地证明，临床定义的CBVD大大低估了CBVD的真实人口负担。我们对美国印第安人心血管疾病(AIS)的大部分了解来自强心研究(SHS)，这是一项对来自13个部落的4549名老年人进行的前瞻性研究，跟踪调查了18年。它进行了体检、实验室和心脏研究，并进行了图表审查，以描述心血管疾病发病率和死亡率的风险因素、患病率和发病率。最近的分析估计，根据美国成年人口的年龄和性别分布调整后，SHS的年龄和性别调整后的中风发病率为679/10万人。这一发病率是在普通人群中观察到的两倍多，表明人工智能正在经历CBVD的流行。然而，人工智能没有包括在CHS或ARIC或其他基于社区的CBVD研究中，SHS也没有进行核磁共振检查。我们将完成临床和MRI评估，以重新评估风险和保护因素，并描述SHS中MRI定义的CBVD。利用幸存的队列成员提供的这些数据，我们将实现我们的具体目标，即：1)估计脑MRI结果定义的CBVD的患病率和量化程度，特别是脑白质高信号、脑梗塞、出血和脑萎缩；2)评估风险因素与常见的MRI定义的CBVD的关系，如人口、生活方式、临床、实验室、超声和超声指标，以及文化适应和印度传统程度的独特影响；以及3)记录MRI定义的CBVD与运动缺陷、认知障碍和抑郁症状的关联强度，并确定它们是否独立于人口统计、生活方式和实验室测量。中风发生率的升高表明，AIS可能正在遭受隐匿性CBVD的巨大负担。作为对CVD进行严格评估的人工智能样本，SHS队列是研究CBVD及其表现的理想选择。在最初的4549名成员中，只有1,950名成员在世并能够参与；自上次提交以来，已有283名成员死亡。目前尚无其他机会让认可机构掌握有关CBVD的资料。现在迫切需要启动这项研究，因为随着时间的推移，最初队列中幸存的成员越来越少。

DESCRIPTION (provided by applicant): Cerebrovascular disease (CBVD), a leading cause of morbidity and mortality, is linked to cognitive and motor impairment, and depression. Magnetic resonance imaging (MRI) has redefined CBVD in large cohort studies, such as the Cardiovascular Health Study (CHS) and Atherosclerosis Risk in Communities (ARIC). In CHS and ARIC, MRI revealed high prevalences of brain abnormalities, specifically white matter hyperintensities, infarcts, and hemorrhages, in populations without known stroke or transient ischemic attack. Further, overt CBVD, such as stroke, was strikingly less common than covert MRI-defined brain disease. The covert findings were not, however, benign accompaniments of aging as they were associated with impaired motor function and cognition, depression, and a striking increase in the risk of subsequent stroke and death. These studies have convincingly demonstrated that clinically-defined CBVD dramatically underestimates the true population burden of CBVD. Much of what we know about cardiovascular disease in American Indians (AIs) comes from the Strong Heart Study (SHS), a prospective study of 4,549 older adults from 13 tribes followed over 18 years. It conducted physical exams, laboratory and cardiac studies, and chart reviews to describe risk factors, prevalence, and incidence of cardiovascular disease morbidity and mortality. Recent analyses estimated the age- and gender- adjusted stroke incidence in the SHS as 679/100,000 persons, adjusted to the age and sex distribution of the U.S. adult population. This incidence is over twice that observed in the general population indicating AIs are experiencing an epidemic of CBVD. AIs, however, were not included in CHS or ARIC or the other community- based studies of CBVD, and the SHS did not perform MRIs. We will complete a clinical and MRI evaluation to re- assess risk and protective factors and describe MRI-defined CBVD in the SHS. With these data from surviving cohort members, we will address our Specific Aims which are to: 1) estimate the prevalence and quantify the extent of CBVD defined by brain MRI findings, specifically white matter hyperintensities, infarcts, hemorrhages, and cerebral atrophy; 2) assess the relationship of risk factors with prevalent MRI-defined CBVD such as demographic, lifestyle, clinical, laboratory, echocardiographic, and ultrasound measures, and the unique influence of acculturation and degree of Indian heritage; and 3) document the strength of associations of MRI- defined CBVD with motor deficits, cognitive impairment, and depressive symptoms, and establish if they are independent of demographic, lifestyle, and laboratory measures. The elevated stroke rates suggest that AIs may be suffering from a large burden of covert CBVD. As an AI sample in which CVD has been rigorously assessed, the SHS cohort is ideal for investigating CBVD and its manifestations. Of the original cohort of 4,549 members, only ~1,950 members will be alive and able to participate; 283 have died since the last submission. Other opportunities to gain knowledge on CBVD among AIs are not forthcoming. There is an urgent need to initiate this study now since as every year passes, fewer members of the original cohort survive.