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: 10424409
• 负责人: Kathleen M Hayden
• 金额: $ 377.65万
• 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 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10424409
• 关键词: Address; African American population; Age; Age of Onset; Alzheimer associated neurodegeneration; Alzheimer disease prevention; Alzheimer' s Disease; Alzheimer' s disease pathology; 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; Cardiovascular Diseases; Cerebral small vessel disease; Cerebrovascular Circulation; Cerebrovascular Disorders; Cerebrum; Chinese; Clinical; Cognition; Data; Data Collection; Dementia; Development; Diagnosis; Elderly; Epigenetic Process; Ethnic Origin; Ethnic group; Future; Gender; Genomics; Health; Heterogeneity; High Prevalence; Hippocampus (Brain); Hispanic; Hispanic Populations; Impaired cognition; Incidence; Intervention; Knowledge; Link; Magnetic Resonance Imaging; Measurement; Measures; Mechanics; Metabolic; 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; brain magnetic resonance imaging; cardiac magnetic resonance imaging; cardiovascular disorder risk; cerebral artery; cerebral atrophy; cerebral microvasculature; cognitive change; cognitive testing; cohort; cost effective; data sharing; ethnic diversity; ethnic minority population; falls; forest; hemodynamics; high risk; improved; metabolomics; mouse model; multi-ethnic; multimodal neuroimaging; multiple omics; new therapeutic target; pre-clinical; prevent; racial and ethnic; solute; tonometry; uptake; vascular contributions; vascular factor; vascular risk factor; β-amyloid burden

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 改善血管健康是延缓阿尔茨海默病发病的关键潜在策略 (Ad)。然而，作为连接血管的特定机制的血管靶点很少。 阿尔茨海默病的功能障碍仍不清楚。在美国，种族/少数民族群体的比例更高 血管负担增加，罹患阿尔茨海默病(AD)的风险增加一倍以上。此外， 最近的数据证实，非洲裔美国人也有更大的风险患有更高的大脑 β-淀粉样蛋白(Aβ)负担比白人更重。然而，几乎没有做过多少工作来描述这种增加的风险 对于不同种族/民族的阿尔茨海默病，人们对他们为什么会有更大的风险知之甚少 广告。动脉僵硬正在成为老年痴呆症的关键血管风险因素，通过 与AD相关病理的多个方面的关系，包括：脑小血管疾病，β- 易患阿尔茨海默病的区域淀粉样蛋白沉积和脑萎缩。然而，我们在认识上的差距 这一机制依然存在。到目前为止，还没有现有的研究有足够的数据来直接连接动脉 通过对脑血流的影响来评价AD病理方面的僵硬程度 在一个多民族的队列中建立联系。我们建议通过以下方式解决我们知识中的这些差距 利用&gt；15年来自多种族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(MESA)。《MESA多站点AD研究》将增加：a)重复、详细 认知评估，以判定认知并评估认知随时间的变化；b)重复 磁共振成像用于评估神经退行性变、脑血管疾病和脑血流灌注；和d)β-PET 成像以量化β负担。MESA多站点AD研究将贡献重要的发现和独特的 与AD病理和认知功能减退相关的先期亚临床血管疾病的资源。 具体地说，它将解决动脉僵硬和血流动力学途径变化对AD- 相关病理学。对于研究人员来说，这种方法将是一种高效且具有成本效益的开放资源 确定AD和Will的可改变的血管和代谢危险因素(超过15年) 帮助指导为各种形式的癌症制定新的治疗目标或预防策略 广告相关的痴呆症。

项目成果

Subclinical Vascular Composites Predict Clinical Cardiovascular Disease, Stroke, and Dementia: The Multi-Ethnic Study of Atherosclerosis (MESA).

亚临床血管复合材料可预测临床心血管疾病、中风和痴呆：动脉粥样硬化的多种族研究 (MESA)。

• DOI: 10.1101/2023.05.01.23289364
• 发表时间: 2023
• 期刊: medRxiv : the preprint server for health sciences
• 作者: Hughes,TimothyM;Tanley,Jordan;Chen,Haiying;Schaich,ChristopherL;Yeboah,Joseph;Espeland,MarkA;Lima,JoaoAC;Ambale-Venkatesh,Bharath;Michos,ErinD;Ding,Jingzhong;Hayden,Kathleen;Casanova,Ramon;Craft,Suzanne;Rapp,StephenR;Luc
• 通讯作者: Luc