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

中年心血管疾病对年轻老年人阿尔茨海默病病理学和脑血管反应性的作用。

• 批准号: 9077314
• 负责人: Ann D. Cohen
• 金额: $ 65.73万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-15 至 2021-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9077314
• 关键词: Age; Aging; Alzheimer' s Disease; Alzheimer' s disease risk; Amyloid; Amyloid beta-Protein; Amyloid deposition; Area; Arteriosclerosis; Atherosclerosis; Atrial Fibrillation; Blood Vessels; Brain; Cardiovascular Diseases; Cerebrovascular Circulation; Clinical; Clinical Markers; Cognition; Communities; Coronary Arteriosclerosis; Data; Dementia; Development; Disease; Disease Progression; Elderly; Evaluation; Evaluation Studies; Exhibits; Failure; Functional disorder; Goals; Heart; Hypercapnia; Hypertension; Image; Impaired cognition; Incidence; Individual; Inflammation; Link; Lipids; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Mediating; Myocardial Ischemia; Nerve Degeneration; Participant; Pathology; Pathway interactions; Peripheral; Physiology; Positron-Emission Tomography; Prevalence; Prevention; Reporting; Risk; Risk Factors; Role; Spin Labels; Structure; Syndrome; Therapeutic; abeta deposition; age related; arterial stiffness; base; cardiovascular disorder risk; cerebral atrophy; cerebrovascular; cognitive change; cohort; middle age; non-demented; post gamma-globulins; pre-clinical; public health relevance; racial disparity; research clinical testing; response; retention rate; tau Proteins

 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.

 描述（由申请人提供）：阿尔茨海默病（AD）的患病率与心血管疾病（CaVD）的存在密切相关，了解β淀粉样蛋白（Aβ）病理学与CaVD之间的关系至关重要。本研究的总体目标是进一步了解AD病理学（包括Aβ和tau病理学）与神经变性、脑血管反应性和中年CaVD之间的关系。为了实现这些目标，我们将利用来自正在进行的基于社区的心脏策略集中于风险评估（心脏评分）研究的现有队列的一组非痴呆参与者，这是一项纵向研究，始于2003年，有2000名参与者（43%黑人），年龄在45-75岁之间，研究进入时，收集了大量的纵向血管测量数据。我们假设中年时发现的亚临床CaVD与阿尔茨海默病病理学风险增加相关，表现为淀粉样蛋白沉积和神经变性。大脑结构的这些变化将与横向和纵向的认知变化有关。我们进一步假设，认知的变化将导致血管代偿反应的失败，其标志是局部脑血流量和脑血管反应性的增加。