Role of midlife cardiovascular disease on Alzheimer’s Pathology and cerebrovascular reactivity in the young-old.

 描述(申请人提供)：阿尔茨海默病(AD)的流行与心血管疾病(CAVD)的存在密切相关，了解淀粉样β蛋白(Aβ)病理与心血管疾病之间的关系至关重要。本研究的主要目的是进一步了解AD病理，包括Aβ和tau病理与神经退行性变、脑血管反应性和中年CAVD的关系。为了实现这些目标，我们将从正在进行的基于社区的心脏策略专注于风险评估(心脏评分)研究的现有队列中利用一组非痴呆症参与者，这是一项始于2003年的纵向研究，研究开始时有2000名参与者(43%是黑人)，年龄在45-75岁之间，并收集了大量纵向血管测量数据。我们假设，在中年发现的亚临床CAVD与阿尔茨海默病的风险增加有关，阿尔茨海默病病理表现为淀粉样沉积和神经变性。大脑结构的这些变化将与认知的横向和纵向变化相关联。我们进一步假设，认知的改变将是血管代偿反应失败的结果，其标志是局部脑血流量和脑血管反应性的增加。

 DESCRIPTION (provided by applicant): The prevalence of Alzheimer's disease (AD) is closely related to the presence of cardiovascular disease (CaVD), understanding the relationship between amyloid-beta (Aβ) pathology and CaVD is critically important. The overarching goal of this study is to further the understanding of the relationship between AD pathology, including Aβ and tau pathology and neurodegeneration, cerebrovascular reactivity and midlife CaVD. To achieve these goals, we will utilize a group non-demented participants from an existing cohort from the ongoing community-based Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) study, a longitudinal study that began in 2003 with a cohort of 2000 participants (43% black) between the ages of 45-75 years at study entry and has collected a wealth of longitudinal vascular measures. We hypothesize that subclinical CaVD identified in midlife is associated with increased risk for Alzheimer's disease pathology expressed as amyloid deposition and neurodegeneration. These changes in brain structure would be associated with alterations in cognition both cross-sectionally and longitudinally. We further hypothesize that the change in cognition will result from a failure of vascular compensatory responses, marked by increases in regional cerebral blood flow and cerebrovascular reactivity.