Core G: MESA Core

MESA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)痴呆症有效。因此，该领域拥有 将重点转移到制定预防、早期干预和早期先兆识别的战略 预测晚年易患痴呆症的生物标志物和风险因素。要解决这些问题 重要的科学目标，现有的老年人队列--在中老年方面有很好的特点 代谢和血管风险因素-将被纳入维克森林ADCC。《红楼梦》的多民族研究 动脉粥样硬化(MESA)是对亚临床和偶发的血管和代谢性疾病的多部位研究，以及 维克森林是六个临床地点之一。MESA和ADCC之间的这种伙伴关系提供了一个独特的 利用MESA参与者的纵向特征来补充和扩展我们的 中心的主题集中在代谢和血管对阿尔茨海默病和其他相关疾病的致病作用 精神错乱。2000年，734名年龄在58岁至97岁之间的成年人(46%是非洲裔美国人，54%是非西班牙裔高加索人)， 加入了维克森林台地队列。参与者经历了广泛的新陈代谢 表型(例如，空腹血糖、胰岛素、血红蛋白A1C、脂粒大小、血浆脂组和 代谢分析)；血管表型(例如，动脉僵硬、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特征；重复视网膜成像， 并在2010-2012年进行了一次简短的认知评估。ADCC MESA核心将增加临床和认知能力 评估(统一数据集和补充认知测试)；神经成像(核磁共振、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，我们将能够招收540名MESA 参与者在获奖期的头两年内，并在三年后重复评估，如 在P30 RFA中推荐用于实现以下特定目标：1)评估临床、认知和 MESA参与者的神经学终点，以确定MCI、AD、VCI和其他相关疾病的特征，并 促进专注于认知状态与先期代谢和血管之间关系的研究 危险因素；2)对MESA核心参与者进行纵向跟踪，以允许检查前驱因素 代谢和血管生物标记物，预测认知和生物标记物的轨迹(下降和恢复能力)， 事件MCI和AD/VCI；3)提供多维数据和其他资源，以促进系统和 遗传、表观遗传和表型数据的路径分析，以确定代谢和血管路径 预测痴呆风险，并阐明AD和VCI之间的临床和病理生理关系，以 为开发新的生物标志物和治疗靶点提供信息；以及4)提供资源以促进 研究种族对代谢和血管关系的潜在影响 通路、认知功能和AD/VCI生物标记物。

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.