Core B: Clinical Core

临床核心(核心B)-项目摘要 Wake ADCC将重点研究代谢和血管风险因素促进 从正常衰老过渡到MCI，然后过渡到AD或其他形式的病理性脑老化，如血管 认知障碍(VCI)。Wake ADCC临床核心将提供对这一重点至关重要的资源， 通过登记、集中描述和跟踪因存在以下情况而处于AD高危状态的成年人 糖尿病前期是一种与代谢和血管病理相关的流行疾病，它增加了患糖尿病的风险 AD和其他痴呆症。我们将注册并跟踪4组参与者：1)认知正常 血糖正常的成年人；2)认知正常的糖尿病前期成年人；3)血糖正常的MCI成年人；以及4) 患有MCI和糖尿病前期的成年人。我们还将注册患有AD的成年人并确定其特征，以参与正在进行的 试验，但考虑到我们的重点是早期过渡，不会在这一组进行密集的纵向表型分析。 参与者将具有仔细的纵向表征，使用补充数据来增强统一数据集 认知测量；脑脊液、DNA和血液的收集和存档；以及使用专门序列的核磁共振成像 对血管端点进行成像。所有参与者也将被要求捐赠大脑。子集将收到 匹兹堡化合物B(PIB)的淀粉样蛋白成像和新型FDG-乙酰乙酸酯双示踪剂PET扫描 评估大脑中替代燃料的利用情况。核心将生成一个强大的数据和标本存储库 这将向Wake调查人员以及世界各地的NACC、NCRAD和AD调查人员提供，以 开展AD发病机制和预防的创新性转化研究。目标1：集中招生和 描述一组认知正常、血糖正常或糖尿病前期的成年人，以及血糖正常或 患有MCI的糖尿病前期成年人以及患有AD痴呆的参与者将可用于 干预、生物标记物发现和遗传/表观遗传学分析，从而指数级地扩大 维克森林的临床翻译研究范围。2：提供资源，以确定是否 糖尿病前期的临床核心参与者在认知和AD的测量上随着时间的推移显示出更大的变化 病理，并探讨新的AD和代谢生物标志物与AD，VCI， 和其他障碍。3：最大限度地促进非洲裔美国成年人和不同种族成年人的参与 以及所有中心队列中的种族背景。4：协调大脑的系统收集和归档， 生物光谱、遗传、认知、代谢和成像数据，将促进数据和样本与 NACC、NCRAD、AD中心和其他协作者。5：开发和收集创新的代谢指标 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，我们独特的高风险队列， 我们丰富的数据、成像和生物质谱库将使我们的研究能够加快我们的 了解阿尔茨海默病的早期阶段和其他形式的病理性脑老化。

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.