Clinical Core

临床核心

基本信息

批准号：
10264228
负责人：
DAVID A WOLK
金额：
$ 73.86万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-15 至 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10264228
关键词：
Achievement African American Alzheimer&apos s Disease Alzheimer&apos s disease related dementia Alzheimer&apos s disease risk Attention Autopsy Awareness Biological Biological Markers Brain Caring Cerebrospinal Fluid Cerebrovascular Disorders Cerebrum Classification Classification Scheme Clinical Clinical Data Clinical Research Clinical Trials Cognition Cognitive Collaborations DNA Data Data Set Dementia Disease Doctor of Philosophy Economic Factors Elderly Epigenetic Process Frontotemporal Dementia Genetic Genetic Materials Genomic DNA Genomics Goals Heterogeneity Image Individual Institution International Intervention Studies Lewy Body Disease Light Link Magnetic Resonance Imaging Measures Mechanics Mission Nerve Degeneration Neurofibrillary Tangles Onset of illness Participant Pathologic Pathologist Pathology Phenotype Plasma Positron-Emission Tomography Presenile Alzheimer Dementia Process Research Research Personnel Risk Role Sampling Senile Plaques Site Source System Training Validation White Matter Hyperintensity base biomarker development brain tissue cardiovascular risk factor clinical Diagnosis clinical phenotype cognitive reserve cohort comorbidity data management disease heterogeneity disorder risk education research imaging program in vivo molecular marker neuroimaging neuroimaging marker neuropathology next generation normal aging outreach pre-clinical protein TDP-43 racial and ethnic recruit research study resilience social factors social health determinants sociodemographic factors synuclein tau Proteins

项目摘要

Clinical Core Project Summary The theme of the Penn ADRC is to better understand both the upstream factors and processes that contribute to Alzheimer’s Disease (AD) heterogeneity and the downstream markers critical to characterizing it. The Clinical Core serves as the central node for this thematic mission by deeply characterizing a clinically and demographically diverse cohort (Aim 1). Given the importance of understanding heterogeneity in the context of the entire AD continuum, we will recruit, assess, and longitudinally follow a cohort, the ADRC UDS Cohort, that spans cognitively normal older adults to those with mild dementia. To capture phenotypic diversity and overlap with other neurodegenerative conditions, the cohort includes frontotemporal dementia (FTD), Lewy Body disease, and atypical and early onset AD presentations. In collaboration with the Outreach, Recruitment, and Engagement Core (ORE), recruitment of African Americans, a group poorly represented in AD research, is also a priority and enhances efforts to examine the diversity of factors that contribute to heterogeneity in expression of disease (Aim 3). In the context of the transformation of AD from being defined as a clinical diagnosis to a disease defined by biomarkers, the Penn ADRC embraces the importance of biomarker acquisition and validation. The Clinical Core facilitates these efforts through acquisition of plasma, cerebrospinal fluid, and MRI and PET imaging (Aim 2). These materials and data are obtained in close collaboration with the Biomarker and Neuroimaging Cores and allow for classification of individuals on the basis of the presence or absence of cerebral b-amyloid plaques (A), tau-based neurofibrillary tangles (T), and neurodegeneration (N). Thus, in as many participants as possible, we will obtain biofluid (CSF and plasma) and/or neuroimaging A/T/(N) designation. To capture the role of cerebrovascular disease (CVD) in AD heterogeneity, we will obtain clinical, biofluid, and neuroimaging measures of risk or downstream manifestations of CVD (e.g. white matter hyperintensities). The Clinical Core will also be a source of genetic material and brain tissue obtained in conjunction with the Genomics and Neuropathology Cores, which will be linked to the above biomarker and clinical data. In light of the potential modulating effect on disease risk, phenotype, and resilience versus vulnerability, we will also obtain measures of social determinants of health (SDoH; Aim 4), which potentially will provide a deeper understanding of the role of ethnoracial differences in disease risk and presentation. In addition to the sharing of this rich and diverse dataset and materials with the National Alzheimer’s Coordinating Center (NACC) and with other ADRCs and institutions, the Clinical Core participates in numerous multi-site collaborative clinical research and intervention studies with the goal of advancing care of people with AD/ADRD (Aim 5). Finally, the Clinical Core serves as an important base for training efforts with the Research Education Component to develop the next generation of investigators and clinicians.

临床核心项目总结宾夕法尼亚州 ADRC 的主题是更好地了解上游因素和流程阿尔茨海默病 (AD) 异质性以及对其表征至关重要的下游标记。临床核心作为这一主题任务的中心节点，深入描述了临床和考虑到了解异质性背景下的重要性（目标 1）。在整个 AD 连续体中，我们将招募、评估和纵向跟踪一个队列，即 ADRC UDS 队列，该队列涵盖认知正常的老年人和患有轻度痴呆症的人，以捕获表型多样性和重叠。与其他神经退行性疾病一样，该队列包括额颞叶痴呆 (FTD)、路易体与外展、招募和宣传部门合作进行疾病、非典型和早发型 AD 演示。参与核心（ORE），招募非洲裔美国人，这是一个在 AD 研究中代表性较差的群体，也是一个优先事项，并加强努力审查导致异质性的因素的多样性疾病的表达（目标 3）。在 AD 从被定义为临床诊断转变为由临床诊断定义的疾病的背景下生物标志物，宾夕法尼亚州 ADRC 认识到生物标志物获取和验证的重要性。 Core 通过采集血浆、脑脊液以及 MRI 和 PET 成像来促进这些工作（目标 2）。这些材料和数据是与生物标志物和神经影像学密切合作获得的。核心并允许根据大脑 b 淀粉样蛋白的存在或不存在对个体进行分类斑块 (A)、基于 tau 的神经原纤维缠结 (T) 和神经变性 (N) 因此，在尽可能多的参与者中。如果可能，我们将获得生物流体（脑脊液和血浆）和/或神经影像学 A/T/(N) 名称来捕获。脑血管疾病 (CVD) 在 AD 异质性中的作用，我们将获得临床生物流体和神经影像 CVD 风险或下游表现的测量（例如白质高信号）。也将是与基因组学结合获得的遗传物质和脑组织的来源神经病理学核心，将与上述生物标志物和临床数据相关联。鉴于对疾病风险、表型以及恢复力与脆弱性的潜在调节作用，我们还将获得健康问题社会决定因素的衡量标准（SDoH；目标 4），这可能会提供更深入地了解种族差异在疾病风险和表现中的作用。除了与国家阿尔茨海默氏症中心共享丰富多样的数据集和材料之外，协调中心 (NACC) 以及其他 ADRC 和机构，临床核心参与了许多多地点协作临床研究和干预研究，旨在促进对患有此病的人的护理 AD/ADRD（目标 5）最后，临床核心是研究培训工作的重要基础。教育部分培养下一代研究者和信徒。