Cerebral hemodynamic impairment in symptomatic and asymptomatic Alzheimer's Disease

摘要 阿尔茨海默氏病（AD）正迅速成为一个压倒性的经济和社会负担。据估计 到2050年，将有1380万美国人患有AD， 到2050年，AD和其他痴呆症的临终关怀将增加到1.2万亿美元。尽管重要的作用 AD的脑血管功能，研究AD的无症状阶段脑血管损害， 缺乏拟议的项目通过使用先进的磁共振成像直接解决了这一重要的科学领域 技术研究AD受试者脑血管功能的生物标志物， 临床症状的表现。拟议项目的总体目标是研究AD是否 在AD连续体的早期阶段，病理学与脑血管病理学直接相互作用，以及 脑血管和AD病理对早期AD认知障碍的相对贡献。(1)我们 将使用先进的MR技术测量脑血管反应性（CVR）作为血管病变的生物标志物， 对264名健康青年和中年人进行了功能和学习CVR的测定 受试者（HY）、无AD病理学的认知正常老年人（CN-）、无症状AD受试者（HY） 具有阳性AD病理学（aAD）的认知正常，以及具有以下症状的前驱AD患者： 轻度认知功能障碍并具有阳性AD病理学（pAD）。两年期间CVR的纵向变化 还将研究CN-、aAD和pAD受试者。(2)我们还将研究白色物质的差异 CN-、aAD和pAD组之间的高信号容积和高级弥散指标， 纵向变化及其与CVR的关系。(3)AD和血管病变的相对贡献 对认知能力的影响也将被评估。这项研究的成功实施将提供更好的 了解早期AD病理学与脑血管功能障碍之间的相互作用 AD连续体，最终可能导致有效的多组分治疗的发展 针对AD和血管病理的AD干预。

Abstract Alzheimer's Disease (AD) is rapidly becoming an overwhelming economic and social burden. It is estimated that 13.8 million Americans will have AD in 2050 and the total annual payments for health, long-term, and hospice care for AD and other dementias will increase to $1.2 trillion in 2050. Despite the important role of cerebrovascular function in AD, studies on cerebrovascular impairment in the asymptomatic phase of AD are lacking. The proposed project directly addresses this important scientific area by using advanced MR imaging techniques to study biomarkers of cerebrovascular function in AD subjects both before and after the manifestation of clinical symptoms. The overarching goal of the proposed project is to study whether AD pathology directly interacts with cerebrovascular pathology in the early phases of the AD continuum, as well as the relative contributions of cerebrovascular and AD pathologies to cognitive impairments in early AD. (1) We will use an advanced MR technique for measuring cerebrovascular reactivity (CVR) as a biomarker of vascular function and study CVR in 264 subjects composed of four groups including healthy young and middle-aged subjects (HY), cognitive normal elderly without AD pathology (CN-), asymptomatic AD subjects who are cognitively normal with positive AD pathology (aAD), and prodromal AD patients who are symptomatic with mild cognitive impairment and have positive AD pathology (pAD). Longitudinal changes in CVR over two years in CN-, aAD, and pAD subjects will also be studied. (2) We will also study differences in the white matter hyperintensity volume and advanced diffusion metrics between the CN-, aAD, and pAD groups, their longitudinal changes and relationship with CVR. (3) The relative contributions of AD and vascular pathologies to cognitive performance will also be evaluated. The successful execution of the study will provide a better understanding of the interactions between AD pathology and cerebrovascular dysfunction in the early phases of AD continuum that could eventually lead to the development of effective multi-component therapeutic interventions of AD that target both AD and vascular pathologies.