Core B: Clinical Core

核心 B：临床核心

• 批准号: 9981584
• 负责人: Jeff Douglas Williamson
• 金额: $ 54.51万
• 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/9981584
• 关键词: Acetoacetates; Address; Adult; African American; Alzheimer' s Disease; Alzheimer' s Disease Core Center; Alzheimer' s disease pathology; Amyloid deposition; Archives; Bioenergetics; Biological Markers; Biological Specimen Banks; Blood; Blood Vessels; Brain; Caucasians; Cell Respiration; Cerebrum; Clinical; Clinical Research; Cognition; Cognitive; Collection; DNA; Data; Data Set; Dementia; Disease; Doctor of Philosophy; Early Diagnosis; Enrollment; Epigenetic Process; Evaluation; Genetic; Image; Institution; Insulin Resistance; Intervention; Ketones; Knowledge; Magnetic Resonance Imaging; Measures; Memory impairment; Metabolic; Metabolic Diseases; Methods; Microvascular Dysfunction; Mitochondria; Neurologist; Not Hispanic or Latino; Outcome; Oxidative Phosphorylation; Participant; Pathogenesis; Pathologic; Pathologic Processes; Pathology; Pattern; Phenotype; Physiologic pulse; Pittsburgh Compound-B; Positron-Emission Tomography; Prediabetes syndrome; Prevention; Preventive Intervention; Protocols documentation; Reporting; Research Personnel; Resources; Risk; Role; Specimen; Symptoms; Therapeutic Intervention; Time; Tracer; Training; Translational Research; Vascular Cognitive Impairment; Vascular Diseases; aging brain; amyloid imaging; biomarker discovery; cohort; data warehouse; experience; forest; glucose metabolism; high risk; indexing; innovation; metabolic imaging; metabolic phenotype; metabolic rate; nervous system disorder; neuroimaging; neuropathology; normal aging; novel; racial and ethnic; racial diversity; recruit; serial imaging; success; vascular risk factor

Clinical Core (Core B) – Project Summary The Wake ADCC will focus on the hypothesis that metabolic and vascular risk factors promote the transition from normal aging to MCI, and then to AD or other forms of pathological brain aging such as vascular cognitive impairment (VCI). The Wake ADCC Clinical Core will provide resources that are pivotal to this focus, by enrolling, intensively characterizing, and following adults who are at high risk of AD due to the presence of prediabetes, a prevalent condition associated with metabolic and vascular pathology, that increases the risk of AD and other dementias. We will enroll and follow 4 groups of participants: 1) cognitively normal normoglycemic adults; 2) cognitively normal adults with prediabetes; 3) normoglycemic adults with MCI; and 4) adults with MCI and prediabetes. We will also enroll and characterize adults with AD to participate in ongoing trials, but given our focus on early transition, will not carry out intensive longitudinal phenotyping in this group. Participants will have careful longitudinal characterization, augmenting the Uniform Dataset with supplemental cognitive measures; collection and archiving of CSF, DNA, and blood; and MRI using specialized sequences to image vascular endpoints. All participants will also be approached for brain donation. A subset will receive amyloid imaging with Pittsburgh Compound B (PiB) and a novel FDG-Acetoacetate dual tracer PET scan to assess alternate fuel utilization in the brain. The Core will generate a powerful data and specimen repository that will be available to Wake investigators as well as NACC, NCRAD, and AD investigators world-wide to conduct innovative translational research on AD pathogenesis and prevention. Aim 1: To enroll and intensively characterize a cohort of cognitively normal normoglycemic or prediabetic adults, and normoglycemic or prediabetic adults with MCI, as well as participants with AD dementia who will be available for novel interventions, biomarker discovery, and genetic/epigenetic analyses, thereby exponentially expanding the scope of clinical-translational research at Wake Forest. 2: To provide resources that will determine whether Clinical Core participants with prediabetes show greater change over time on measures of cognition and AD pathology, and to explore relationships among novel AD and metabolic biomarkers and symptoms of AD, VCI, and other disorders. 3: To maximize the participation of African American adults and adults from diverse racial and ethnic backgrounds in all Center cohorts. 4: To coordinate systematic collection and archiving of brain, biospecimen, genetic, cognitive, metabolic, and imaging data that will facilitate data and specimen sharing with NACC, NCRAD, AD Centers and other collaborators. 5: To develop and collect innovative indices of metabolic and vascular risk that will be used to assess Core participants and whose protocols will be made available to investigators at Wake Forest and other institutions. These innovative methods, our unique risk-enriched cohort, and our extensive data, imaging, and biospecimen repository will enable studies to accelerate our understanding of the earliest stages of AD and other forms of pathological brain aging.

临床核心（核心B）-项目总结 Wake ADCC将重点关注代谢和血管危险因素促进 从正常老化过渡到MCI，然后过渡到AD或其他形式的病理性脑老化，如血管性脑老化， 认知障碍（VCI）。唤醒ADCC临床核心将提供对这一重点至关重要的资源， 通过招募、集中表征和随访由于存在以下因素而处于AD高风险的成年人， 糖尿病前期，一种与代谢和血管病理学相关的普遍病症，其增加了 AD和其他痴呆症。我们将招募并随访4组受试者：1）认知正常 正常血糖成年人; 2）认知正常的糖尿病前期成年人; 3）正常血糖的MCI成年人;和4） MCI和前驱糖尿病患者。我们还将招募和描述AD成人，以参与正在进行的 试验，但考虑到我们的重点是早期过渡，将不会进行密集的纵向表型在这一组。 参与者将进行仔细的纵向特征描述，通过补充数据来增强统一数据集， 认知测量; CSF、DNA和血液的收集和存档;以及使用专门序列的MRI， 成像血管终点。所有参与者也将接受大脑捐赠。一个子集将接收 匹兹堡化合物B（PiB）淀粉样蛋白成像和一种新的FDG-乙酰乙酸双示踪PET扫描， 评估大脑中替代燃料的利用率。核心将产生一个强大的数据和标本库 将提供给Wake调查人员以及NACC、NCRAD和全球AD调查人员， 开展AD发病机制和预防的创新转化研究。目标1：注册和强化 表征认知正常血糖正常或糖尿病前期成人的队列，以及血糖正常或 患有MCI的糖尿病前期成年人，以及将接受新的 干预，生物标志物发现和遗传/表观遗传分析，从而指数级地扩大了 维克森林的临床转化研究范围。2：提供资源，以确定是否 患有前驱糖尿病的临床核心参与者在认知和AD指标上随时间推移表现出更大的变化 病理学，并探索新的AD和代谢生物标志物与AD症状，VCI， 和其他疾病。3：最大限度地扩大非裔美国人和不同种族的成年人的参与， 和种族背景。4：协调大脑的系统收集和存档， 生物标本、遗传、认知、代谢和成像数据，这些数据将促进与 NACC，NCRAD，AD中心和其他合作者。5：开发和收集代谢的创新指标 和血管风险，将用于评估核心参与者，其方案将提供给 维克森林和其他机构的调查人员。这些创新的方法，我们独特的风险丰富的队列， 我们广泛的数据、成像和生物标本库将使研究能够加速我们的研究。 了解AD的早期阶段和其他形式的病理性脑老化。