Subclinical Vascular Contributions to Alzheimer's Disease: The Multi Ethnic Study of Atherosclerosis (MESA) Multisite Studyof AD

项目摘要 改善血管健康是延迟阿尔茨海默病发作的关键潜在策略 （AD）。然而，作为连接血管的特异性机制的血管靶点很少， 功能障碍与AD的关系尚不清楚。美国的少数民族/种族群体有更高的 血管负担和超过两倍的风险发展阿尔茨海默病（AD）。此外，本发明还 最近的数据证实，非洲裔美国人也有更高的脑血管疾病风险， β-淀粉样蛋白（Aβ）负荷高于白人。然而，几乎没有工作已经做了表征增加的风险 对于不同种族/民族群体中的AD，很少有人知道“为什么”他们具有更大的风险， AD.动脉僵硬正在成为老年痴呆症的一个关键血管危险因素， 与AD相关病理学的各个方面相关，包括：脑小血管疾病、β- 淀粉样蛋白沉积和AD易感区域的脑萎缩。然而，我们对这些问题的理解 这一机制仍然存在。到目前为止，没有现有的研究有足够的数据直接连接动脉 通过其对脑血流量的影响或评估AD病理学方面的硬度 在多民族的群体中。我们建议通过以下方式填补我们知识中的这些空白： 利用来自多民族的超过15年的高度详细和无与伦比的纵向血管数据， 动脉粥样硬化研究（梅萨）。“梅萨多地点AD研究”将添加：a）重复、详细 认知评估，以判定认知并评估随时间的认知变化; B）重复 评估神经变性、脑血管疾病和脑灌注的MRI;和d）Aβ-PET 成像以量化Aβ负荷。“梅萨多站点广告研究”将提供关键发现和独特的 与AD病理学和认知能力下降有关的亚临床血管疾病的资源。 具体来说，它将解决动脉僵硬度和血液动力学途径的变化对AD的作用， 相关病理学这种方法将是一个有效的和具有成本效益的开放资源的研究人员 确定AD的先前可改变的血管和代谢风险因素（>15年），并将 帮助指导开发新的治疗靶点或预防各种形式的 AD相关痴呆

Project Summary Improving vascular health is a critical potential strategy to delay the onset of Alzheimer's disease (AD). However, there are few vascular targets as the specific mechanisms linking vascular dysfunction to AD remain unclear. Racial/ethnic minority groups in the United States have a higher vascular burden and more than a two-fold risk of developing Alzheimer's disease (AD). Further, recent data has confirmed that African-Americans also have a greater risk of having higher cerebral β-amyloid (Aβ) burden than Whites. Yet, little work has been done to characterize the increased risk for AD among different racial/ethnic groups and little is known about `why' they carry a greater risk for AD. Arterial stiffness is emerging as a key vascular risk factor for late life dementia, through associations with various aspects of AD-related pathology including: cerebral small vessel disease, β- amyloid deposition and brain atrophy in AD-prone regions. However, gaps in our understanding of this mechanism remain. To date, no existing studies have adequate data to directly connect arterial stiffness to aspects of AD pathology through its effects on cerebral blood flow or to evaluate the association in a multi-ethnic cohort. We propose to address these gaps in our knowledge by leveraging >15 years of highly detailed and unparalleled longitudinal vascular data from Multi-Ethnic Study of Atherosclerosis (MESA). The `MESA Multisite AD study' will add: a) repeated, detailed cognitive assessments to adjudicate cognition and assess cognitive changes over time; b) repeated MRIs to assess neurodegeneration, cerebrovascular disease and cerebral perfusion; and d) Aβ-PET imaging to quantify Aβ burden. The `MESA Multisite AD study' will contribute key findings and unique resources relating antecedent subclinical vascular disorders to AD pathology and cognitive decline. Specifically, it will address the role of changes arterial stiffness and hemodynamic pathways to AD- related pathology. This approach will be an efficient and cost-effective open-resource for researchers to identify antecedent modifiable vascular and metabolic risk factors (over >15 years) for AD and will help guide the development of novel therapeutic targets or prevention strategies for various forms of AD-related dementias.