ADRC Consortium for Clarity in ADRD Research Through Imaging

ADRC 联盟通过成像来明确 ADRD 研究

• 批准号: 10803806
• 负责人: BRADFORD C DICKERSON
• 金额: $ 3080万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-15 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10803806
• 关键词: Accounting; Address; Age of Onset; Alzheimer' s Disease; Alzheimer' s disease related dementia; Amyloid; Amyloid beta-42; Amyloid beta-Protein; Autopsy; Biological Assay; Biological Markers; Blood Vessels; Brain; Classification; Clinical; Clinical Data; Cognitive; Cohort Studies; Collection; Consensus; Data Collection; Data Set; Dementia; Diagnosis; Diagnostic; Disclosure; Disease; Ecosystem; Enrollment; Ensure; Etiology; Foundations; Functional disorder; Future; Genetic; Glial Fibrillary Acidic Protein; Heterogeneity; Image; Impaired cognition; Impairment; Individual; Infrastructure; Investigational Therapies; Ischemia; Joints; Label; Lewy Bodies; Link; Literature; Longitudinal Studies; MRI Scans; Magnetic Resonance Imaging; Measures; Metabolic; Methods; Microvascular Dysfunction; Modeling; Morphology; Motion; Nerve Degeneration; Outcome; Participant; Pathology; Patients; Pattern; Perfusion; Phenotype; Plasma; Positioning Attribute; Positron-Emission Tomography; Predisposition; Process; Protocols documentation; Research; Resource Sharing; Resources; Severities; Site; Source; Standardization; Symptoms; Syndrome; System; Techniques; Time; Underrepresented Populations; Validation; Vascular Diseases; Visual; Work; adjudication; aging brain; alpha synuclein; astrogliosis; burden of illness; clinical heterogeneity; cognitive change; cohort; data sharing; design; diagnostic accuracy; fluorodeoxyglucose positron emission tomography; imaging biomarker; imaging study; improved; in vivo; in vivo imaging; ischemic lesion; mild cognitive impairment; mixed dementia; neurobehavioral; neuropathology; patient engagement; programs; prospective; protein TDP-43; recruit; response; serial imaging; shared repository; success; tau Proteins; therapeutic development; tool; treatment trial

PROJECT SUMMARY Alzheimer’s disease (AD) pathophysiology seldom occurs in isolation, and it is widely established from the neuropathology literature that the majority of individuals with dementia have multiple etiology dementia (MED). MED is common but undetected in extant major cohort studies and treatment trials for AD; many studies intentionally restrict clinical heterogeneity to an assumed single etiology by using narrowly defined clinical enrollment criteria. A major gap in our field is the lack of validated tools to detect MED in-vivo. The next era of large-scale imaging biomarker studies for AD and related disorders (ADRD) will require strategies commensurate with the known but largely unaddressed problem of etiologic heterogeneity. The Alzheimer’s Disease Research Centers (ADRCs) are uniquely positioned to meet this need. Collectively the 37 ADRCs follow ~14,000 active enrollees with high brain donor and autopsy rates (>60%). The ADRCs recruit across the clinical severity continuum and amply represent the several diseases comprising ADRD. Now, as a consortium, the centers will conduct a uniform imaging protocol capable of elucidating individualized etiological profiles including foundational PET imaging for AD proteinopathy (Amyloid and Tau), vascular burden with MRI and additional structural MRI and FDG PET for assessing the several patterns of morphologic and metabolic Neurodegeneration signatures of both AD and non-AD proteinopathies on deeply phenotyped patients. Design: This is a longitudinal imaging study at 2-year intervals that is superimposed on and fully integrated with the ongoing uniform cognitive and clinical data collection the 37 ADRCs already do. We will study 2,000 ethnoculturally diverse ADRC participants that are either clinically unimpaired (CU; N=800) or impaired (N=1,200) where AD is a considered, though need not be the primary suspected etiology. Aim 1 creates the ATN cohort through prospective imaging and plasma collection and establishes the foundational shared resource in conjunction with the National Alzheimer’s Coordinating Center (NACC) with linkage to the vast clinical, cognitive, and genetic datasets on these same participants. In Aim 2 we examine the temporal progression of the two most common etiologies—AD and vascular disease. We examine onset ages and duration of each and their joint effect on cognitive decline. Aim 3 focuses on other common proteinopathies. Classification and joint modelling methods will be applied to estimate etiologic composition and the effect of multi-proteinopathy on clinical and cognitive change. ATN imaging–a critical foundation for characterizing likely dementia etiologies—is needed on this expertly-diagnosed, uniformly evaluated MED ADRD cohort where neuropathology can inform clinicopathologic correlation, mechanistic underpinnings, and strategic diagnostic and therapeutic development. The consortium of ADRCs have the expertise and capacity to conduct this study and will work together to ensure its success and its impact on the field.

项目摘要 阿尔茨海默病（AD）的病理生理学很少单独发生，它是从医学上广泛建立的 神经病理学文献表明，大多数痴呆患者患有多病因痴呆（MED）。 MED很常见，但在现有的主要队列研究和AD治疗试验中未检测到;许多研究 通过使用狭义的临床异质性， 入组标准。我们领域的一个主要差距是缺乏有效的工具来检测MED体内。的下一个时代 AD和相关疾病（ADRD）的大规模成像生物标志物研究将需要相应的策略 与已知的，但在很大程度上未解决的问题，病因异质性。老年痴呆症的研究 中心（ADRC）具有独特的定位，以满足这一需求。总共37个ADRC遵循约14，000个活动 脑捐献率和尸检率高（>60%）的入选者。ADRC招募的临床严重程度 连续体和充分代表了包括ADRD的几种疾病。现在，作为一个财团，这些中心将 进行能够阐明个体化病因学特征的统一成像方案，包括 AD蛋白质病（淀粉样蛋白和Tau）的基础PET成像、MRI血管负荷和其他 结构MRI和FDG PET用于评估形态和代谢的几种模式 AD和非AD蛋白病在深度表型患者中的神经变性特征。设计图： 这是一项以2年为间隔的纵向成像研究， 正在进行的统一认知和临床数据收集，37个ADRC已经这样做了。我们将研究2000 临床未受损（CU; N=800）或受损的种族文化多样性ADRC参与者 （N= 1，200），其中AD被认为是主要疑似病因，但不一定是主要疑似病因。目标1创建ATN 队列通过前瞻性成像和血浆收集，并建立基础共享资源， 与国家阿尔茨海默氏症协调中心（NACC）合作，与庞大的临床，认知， 和基因数据集。在目标2中，我们研究了两个最重要的时间进程， 常见病因-AD和血管疾病。我们检查每个和他们的关节的发病年龄和持续时间 对认知能力下降的影响目的3关注其他常见的蛋白质病。分类和联合建模 方法将被应用于估计病因组成和多蛋白病对临床和 认知改变ATN成像-表征可能的痴呆病因的关键基础-是需要的， 这个经过专业诊断、统一评估的MED ADRD队列，神经病理学可以告知 临床病理学相关性、机制基础以及战略性诊断和治疗发展。 ADRC联合体拥有开展这项研究的专业知识和能力，并将共同努力，确保 它的成功及其对该领域的影响。