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

亚临床血管对阿尔茨海默氏病的影响：动脉粥样硬化多种族研究 (MESA) AD 多地点研究

• 批准号: 9759739
• 负责人: Kathleen M Hayden
• 金额: $ 357.31万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-15 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9759739
• 关键词: Address; African American; Age; Age of Onset; Alzheimer disease prevention; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Alzheimer’s disease biomarker; Amyloid beta-Protein; Amyloid deposition; Ancillary Study; Arteries; Biological Markers; Blood Vessels; Brain; Cardiac; Cardiovascular Diseases; Cerebral small vessel disease; Cerebrovascular Circulation; Cerebrovascular Disorders; Cerebrum; Chinese People; Clinical; Cognition; Data; Data Collection; Dementia; Development; Diagnosis; Elderly; Epigenetic Process; Ethnic Origin; Ethnic group; Future; Gender; Genomics; Health; Heterogeneity; High Prevalence; Hippocampus (Brain); Hispanics; Impaired cognition; Incidence; Intervention; Knowledge; Link; Magnetic Resonance Imaging; Measurement; Measures; Mechanics; Metabolic; Minority Groups; Molecular; Multi-Ethnic Study of Atherosclerosis; Nerve Degeneration; Neurocognitive; Outcome; Parents; Participant; Pathology; Pathway interactions; Perfusion; Phenotype; Pittsburgh Compound-B; Policies; Positron-Emission Tomography; Prevalence; Prevention strategy; Proteomics; Race; Research Personnel; Resources; Risk; Risk Factors; Role; Severities; Site; Subgroup; Time; Trans-Omics for Precision Medicine; United States; Vascular Diseases; White Matter Disease; Work; abeta deposition; adjudicate; age related; aged; arterial stiffness; cardiovascular disorder risk; cerebral artery; cerebral atrophy; cerebral microvasculature; cognitive change; cognitive testing; cohort; cost effective; data sharing; ethnic diversity; falls; forest; hemodynamics; high risk; improved; metabolomics; mouse model; multimodality; multiple omics; neuroimaging; new therapeutic target; pre-clinical; prevent; racial and ethnic; solute; tonometry; uptake; vascular contributions; vascular factor; vascular risk factor

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.

项目摘要 改善血管健康是延迟阿尔茨海默氏病发作的关键潜在策略 （广告）。但是，作为连接血管的特定机制几乎没有血管靶标 AD功能障碍仍不清楚。美国的种族/族裔少数群体的群体更高 血管Burnen和患阿尔茨海默氏病（AD）的两倍的风险超过两倍。更远， 最近的数据证实，非裔美国人的大脑具有更大的风险 β-淀粉样蛋白（Aβ）燃烧比白人燃烧。然而，几乎没有做过增加风险的工作 对于不同的种族/族裔群体中的广告，对“为什么”的风险鲜为人知 广告。通过 与广告相关病理的各个方面的关联，包括：脑小血管疾病，β- 淀粉样蛋白沉积和脑萎缩在广告中。但是，我们对我们的理解差距 这种机制仍然存在。迄今为止，尚无现有研究有足够的数据直接连接动脉 通过对脑血流的影响或评估AD病理学方面的僵化 在多种族队列中的关联。我们建议根据我们的知识解决这些差距 利用> 15年的高度详细且无与伦比的纵向血管数据 动脉粥样硬化研究（MESA）。 “台面多站点广告研究”将补充：a）重复，详细的 认知评估，以调整认知和评估的认知变化； b）重复 MRI评估神经退行性，脑血管疾病和脑灌注；和d）aβ-pet 成像以量化AβBurnen。 “台面多站点广告研究”将贡献关键发现和独特的发现 将先前亚临床血管疾病与AD病理学和认知能力下降有关的资源。 具体而言，它将解决变化动脉刚度和血液动力学途径的作用 相关病理。对于研究人员来说，这种方法将是一种有效且具有成本效益的开放资源 确定AD的先决性可修改血管和代谢危险因素（超过15年） 帮助指导开发各种形式的新型治疗靶标或预防策略 广告相关的痴呆症。