Cerebral hemodynamic impairment in symptomatic and asymptomatic Alzheimer's Disease

摘要 阿尔茨海默病(AD)正迅速成为压倒性的经济和社会负担。据估计， 到2050年，1380万美国人将患有阿尔茨海默病，每年的医疗、长期和 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。尽管扮演着重要的角色 阿尔茨海默病的脑血管功能，关于AD无症状期的脑血管损害的研究进展如下 缺乏。拟议的项目通过使用先进的磁共振成像技术直接解决了这一重要的科学领域。 阿尔茨海默病患者治疗前后脑血管功能生物标志物的研究 临床症状表现。拟议项目的总体目标是研究AD是否 在AD的早期阶段，病理学直接与脑血管病理学相互作用，以及 脑血管和AD病理在早期AD认知损害中的相对贡献。(1)我们 将使用先进的磁共振技术测量脑血管反应性(CVR)作为血管生物标记物 健康青壮年四组264名受试者的CVR功能及研究 受试者(HY)，无AD病理的认知正常老年人(CN-)，无症状的AD受试者 认知正常，AD病理阳性(AAD)，以及有症状的前驱AD患者 轻度认知障碍，有阳性的AD病理(PAD)。两年来CVR的纵向变化 在CN-，AAD和PAD科目也将被研究。(2)我们还将研究脑白质的差异 CN-、AAD和PAD组之间的高强度体积和高级扩散度量，其 纵向变化及其与CVR的关系。(3)AD与血管病理的相对贡献 也将对认知表现进行评估。这项研究的成功进行将提供更好的 早期阿尔茨海默病病理与脑血管功能障碍相互作用的认识 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.