Core G: MESA Core

梅萨核心（核心G）-项目摘要 没有任何疗法被证明对阿尔茨海默病（AD）痴呆有效。因此，该领域 将重点转移到制定预防、早期干预和识别早期先兆的战略 生物标志物和风险因素，预测晚年的脆弱性或对痴呆症的恢复力。解决这些 重要的科学目标，现有的老年人群体-在中年到晚年方面有很好的特点 代谢和血管风险因素-将被整合到维克森林ADCC中。多种族研究 动脉粥样硬化（梅萨）是亚临床和偶发血管和代谢疾病的多中心研究， 维克森林是六个临床基地之一。梅萨和ADCC之间的这种伙伴关系提供了一个独特的 有机会利用梅萨参与者的纵向特征，以补充和扩大我们的 中心的主题集中在代谢和血管致病的贡献，AD和其他相关的 紊乱2000年，734名年龄在58至97岁之间的成年人（46%为非洲裔美国人，54%为非西班牙裔高加索人）， 入选维克森林梅萨队列。参与者经历了广泛的代谢 表型分析（例如，空腹血糖、胰岛素、血红蛋白A1 C、脂质颗粒大小、血浆脂质组学和 代谢组学分析）;血管表型（例如，动脉僵硬度，冠状动脉钙化，颈动脉 超声）;全基因组和外显子组测序和表观遗传学表征;重复视网膜成像， 以及2010-2012年的简短认知评估。ADCC梅萨核心将增加临床和认知 评估（统一数据集和补充认知测试）;神经影像学（MRI，淀粉样蛋白PET）;以及 收集脑脊液和大脑在NIA资助的ADCC的支持下，我们将能够招募540名梅萨 参与者在我们的奖励期的前2年内，并在3年后重复评估， P30 RFA中推荐的，以实现以下特定目的：1）评估临床、认知和 梅萨参与者的神经学终点，以表征MCI、AD、VCI和其他相关疾病，并 促进研究，重点是认知状态和前因代谢和血管之间的关系 风险因素; 2）对梅萨核心参与者进行纵向随访，以检查 预测认知和生物标志物轨迹（衰退和恢复力）的代谢和血管生物标志物， 事件MCI和AD/VCI; 3）提供多维数据和其他资源，以促进系统和 对遗传、表观遗传和表型数据进行途径分析，以确定代谢和血管途径 预测痴呆风险，并阐明AD和VCI之间的临床和病理生理关系， 为新的生物标志物和治疗靶点的开发提供信息;以及4）提供资源， 研究种族对代谢和血管之间关系的潜在影响的研究 途径、认知功能和AD/VCI生物标志物。

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.