Core G: MESA Core

核心G：MESA核心

• 批准号: 9753088
• 负责人: Timothy M. Hughes
• 金额: $ 48.76万
• 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
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9753088
• 关键词: Address; Adult; African American; Age; Age-Years; Alzheimer' s Disease; Alzheimer' s Disease Core Center; Amyloid; Award; Biological Markers; Blood Vessels; Brain; Caucasians; Cerebrospinal Fluid; Charge; Clinical; Clinical assessments; Cognitive; Collection; Complement; Data; Data Set; Dementia; Development; Diagnosis; 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; Religion and Spirituality; 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; 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 Core（核心G） - 项目摘要 没有证明对阿尔茨海默氏病（AD）痴呆症有效的疗法。结果，该领域具有 转移的重点是制定预防，早期干预和识别早期先前的策略 生物标志物和风险因素可以预测以后的生活脆弱性或对痴呆症的韧性。解决这些 重要的科学目标，现有的老年人队列 - 在后期生活方面有很好的特征 代谢和血管危险因素 - 将集成到Wake Forest ADCC中。多民族研究 动脉粥样硬化（MESA）是对亚临床和入射血管和代谢疾病的多站点研究， 韦克森林是六个临床部位之一。 MESA与ADCC之间的这种伙伴关系提供了独特的 利用台面参与者的纵向表征完成并扩展我们的机会 中心的主题侧重于代谢和血管对广告和其他相关的致病贡献 疾病。 2000年，有734名58至97岁的成年人（46％的非裔美国人，54％的非西班牙裔高加索人）， 我们被招收到Wake Forest Mesa队列。参与者经历了广泛的代谢 表型（例如，禁食葡萄糖，胰岛素，血红蛋白A1C，脂质粒径，血浆脂质组和 代谢组分析）；血管表型（例如，动脉刚度，冠状动脉钙化，颈动脉 超声波）;整个基因组和外显子组测序和表观遗传表征；再次重复残留成像， 并在2010-2012进行了简短的认知评估。 ADCC MESA核心将增加临床和认知 评估（统一的数据集和补充认知测试）；神经影像学（MRI，淀粉样宠物）；和 CSF和大脑的收集。在NIA资助的ADCC的支持下，我们将能够注册540 Mesa 参与者在我们颁奖期的前两年内并在3年后重复评估， 建议在P30 RFA中完成以下具体目的：1）评估临床，认知和 MESA参与者中的神经终点，以MCI，AD，VCI和其他相关疾病为特征，并 促进研究重点是认知状况与先行代谢和血管之间的关系 风险因素； 2）进行MESA核心参与者的纵向随访，以允许检查先决条件 预测认知和生物标志物轨迹的代谢和血管生物标志物（衰落和弹性）， 事件MCI和AD/VCI； 3）提供多维数据和其他资源来培养系统，以及 遗传，表观遗传和表型数据的途径分析，以识别代谢和血管途径 这可以预测痴呆症风险，并阐明AD和VCI之间的临床和病理生理关系 告知新型生物标志物和治疗靶标的发展； 4）提供促进的资源 调查研究种族对代谢与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。