Core G: MESA Core

核心G：MESA核心

• 批准号: 9981590
• 负责人: STEPHEN R RAPP
• 金额: $ 45.27万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9981590
• 关键词: Address; Adult; African American; Age; Age-Years; Alzheimer' s Disease; Alzheimer' s Disease Core Center; Alzheimer' s disease diagnosis; Amyloid; Award; Biological Markers; Blood Vessels; Brain; Caucasians; Cerebrospinal Fluid; Charge; Clinical; Clinical assessments; Cognitive; Collection; Complement; Data; Data Set; Dementia; Development; Disease; Early Intervention; Early identification; Elderly; Enrollment; Epigenetic Process; Fostering; Functional disorder; Funding; Glycosylated hemoglobin A; Goals; Impaired cognition; Individual; Insulin; Investigation; Lead; Leadership; Length; Letters; Lipids; Magnetic Resonance Imaging; Metabolic; Metabolic Diseases; Monitor; Multi-Ethnic Study of Atherosclerosis; Neurologic; Not Hispanic or Latino; Participant; Particle Size; Pathologic; Pathway Analysis; Pathway interactions; Pharmacology; Phenotype; Plasma; Positron-Emission Tomography; Predictive Factor; Prevention; Prevention strategy; Preventive Intervention; Public Health; Race; Research; Research Personnel; Resources; Risk Factors; Role; Site; Specimen; Systems Analysis; Testing; Time; Treatment Efficacy; Ultrasonography; United States National Institutes of Health; Universities; Vascular Cognitive Impairment; Vascular Diseases; Washington; Woman; aged; aging brain; arterial stiffness; clinical research site; cognitive function; cognitive testing; cohort; coronary artery calcification; dementia risk; exome sequencing; fasting glucose; follow-up; forest; genetic analysis; genome sequencing; lifestyle intervention; metabolic phenotype; metabolomics; mild cognitive impairment; multidimensional data; neuroimaging; new therapeutic target; non-demented; normal aging; novel; novel marker; phenotypic data; predictive marker; racial diversity; ranpirnase; religious order study; resilience; retinal imaging; vascular contributions; vascular risk factor; whole genome

MESA Core (Core G) – Project Summary No therapies have proven effective against Alzheimer's disease (AD) dementia. As a result, the field has shifted focus to develop strategies for prevention, early intervention, and the identification of early antecedent biomarkers and risk factors that predict later life vulnerability or resilience to dementia. To address these important scientific goals, an existing cohort of older adults – well characterized with regard to mid- to later-life metabolic and vascular risk factors – will be integrated into the Wake Forest ADCC. The Multi-Ethnic Study of Atherosclerosis (MESA) is a multi-site study of subclinical and incident vascular and metabolic disease, and Wake Forest is one of six clinical sites. This partnership between MESA and the ADCC provides a unique opportunity to leverage the longitudinal characterization of MESA participants to complement and expand our Center's theme focused on metabolic and vascular pathogenetic contributions to AD and other related disorders. In 2000, 734 adults, aged 58 to 97 years (46% African-American, 54% non-Hispanic Caucasian), were enrolled into the Wake Forest MESA cohort. Participants have undergone extensive metabolic phenotyping (e.g., fasting glucose, insulin, hemoglobin A1C, lipid particle size, plasma lipidomic and metabolomic analyses); vascular phenotyping (e.g., arterial stiffness, coronary artery calcification, carotid ultrasound); whole genome and exome sequencing and epigenetic characterization; repeated retinal imaging, and a brief cognitive assessment in 2010-2012. The ADCC MESA Core will add clinical and cognitive assessments (Uniform Data Set and supplemental cognitive tests); neuroimaging (MRI, amyloid PET); and collection of CSF and brains. With the support of an NIA-funded ADCC, we will be able to enroll 540 MESA participants within the first 2 years of our award period and repeat assessments 3 years later, as recommended in the P30 RFA to accomplish the following Specific Aims: 1) assess clinical, cognitive, and neurological endpoints in MESA participants to characterize MCI, AD, VCI, and other related disorders, and to facilitate research focused on relationships between cognitive status and antecedent metabolic and vascular risk factors; 2) conduct longitudinal follow-up of MESA Core participants to permit examination of antecedent metabolic and vascular biomarkers that predict cognitive and biomarker trajectories (decline and resilience), incident MCI, and AD/VCI; 3) provide multidimensional data and other resources to foster systems and pathway analyses of genetic, epigenetic, and phenotypic data to identify the metabolic and vascular pathways that predict dementia risk, and elucidate the clinical and pathophysiologic relationships between AD and VCI to inform the development of novel biomarkers and therapeutic targets; and 4) provide resources to facilitate investigations examining the potential impact of race on relationships between metabolic and vascular pathways, cognitive function, and AD/VCI biomarkers.

MESA 核心（核心 G）——项目摘要 目前还没有任何疗法被证明对阿尔茨海默病 (AD) 痴呆症有效。结果，该领域有 将重点转向制定预防、早期干预和识别早期前因的策略 预测晚年痴呆症脆弱性或恢复力的生物标志物和风险因素。为了解决这些 重要的科学目标，现有的老年人群体——中晚年的特征 代谢和血管危险因素——将被纳入维克森林 ADCC。多民族研究 动脉粥样硬化 (MESA) 是一项针对亚临床和偶发性血管和代谢疾病的多中心研究， 维克森林是六个临床中心之一。 MESA 和 ADCC 之间的这种伙伴关系提供了独特的 有机会利用 MESA 参与者的纵向特征来补充和扩展我们的 中心的主题侧重于代谢和血管发病对 AD 及其他相关疾病的贡献 失调。 2000 年，734 名年龄在 58 岁至 97 岁之间的成年人（46% 为非洲裔美国人，54% 为非西班牙裔白种人）， 被纳入维克森林 MESA 队列。参与者经历了广泛的新陈代谢 表型分析（例如空腹血糖、胰岛素、血红蛋白 A1C、脂质颗粒大小、血浆脂质组学和 代谢组分析）；血管表型（例如动脉僵硬度、冠状动脉钙化、颈动脉 超声波）;全基因组和外显子组测序以及表观遗传表征；重复视网膜成像， 以及 2010-2012 年的简短认知评估。 ADCC MESA 核心将增加临床和认知功能 评估（统一数据集和补充认知测试）；神经影像（MRI、淀粉样蛋白 PET）；和 收集脑脊液和大脑。在 NIA 资助的 ADCC 的支持下，我们将能够注册 540 MESA 奖励期前 2 年内的参与者并在 3 年后重复评估，如 P30 RFA 中建议实现以下具体目标：1) 评估临床、认知和 MESA 参与者的神经学终点，以表征 MCI、AD、VCI 和其他相关疾病，并 促进专注于认知状态与先前代谢和血管之间关系的研究 风险因素； 2) 对 MESA 核心参与者进行纵向随访，以检查前因 预测认知和生物标记轨迹（衰退和恢复）的代谢和血管生物标记， 事件 MCI 和 AD/VCI； 3）提供多维数据和其他资源来培育系统和 对遗传、表观遗传和表型数据进行通路分析，以确定代谢和血管通路 预测痴呆风险，并阐明 AD 和 VCI 之间的临床和病理生理关系 为新型生物标志物和治疗靶点的开发提供信息； 4）提供资源以促进 研究种族对代谢和血管之间关系的潜在影响 途径、认知功能和 AD/VCI 生物标志物。