Core F: University of Kentucky Alzheimer's Disease Core Center

核心F：肯塔基大学阿尔茨海默病核心中心

• 批准号: 10662361
• 负责人: Donna M Wilcock
• 金额: $ 56.65万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10662361
• 关键词: Adopted; Alzheimer' s Disease; Alzheimer' s Disease Core Center; Alzheimer’s disease biomarker; Biological Markers; Blood; Brain Pathology; Cerebral small vessel disease; Clinical; Cognitive; Collection; Complex; Consensus; Data; Dementia; Digital biomarker; Disease; Elderly; Etiology; Gait; Goals; Image; Impaired cognition; Individual; Inflammation; International; Ischemia; Kentucky; Lewy Body Dementia; Lewy body pathology; Liquid substance; Longitudinal cohort; MRI Scans; Magnetic Resonance Imaging; Measures; Modality; Participant; Pathologic; Pathology; Physical activity; Plasma; Positron-Emission Tomography; Research; Research Project Grants; Role; Sleep; Sleep disturbances; Standardization; System; Universities; aging population; biomarker development; biomarker identification; biomarker performance; blood-based biomarker; clinic ready; cohort; digital; insight; interest; meetings; multimodality; neuroinflammation; normal aging; novel; novel marker; precision medicine; wearable device

Project Summary/Abstract: Biomarker Core The theme of our UK-ADRC is Transitions from normal to late-life multi-etiology dementia, and the role of the Biomarker Core is to provide data and support efforts to develop biomarker profiles for the spectrum of underlying pathologies that can contribute to an individual’s cognitive decline. The Biomarker core will provide critical characterization of our cohort during their cognitively normal state, and through their cognitive transitions. The utility of biomarkers is expanding rapidly, as the dementia field identifies potentially disease- modifying therapies. Rather than focusing on a single biomarker modality (i.e. MRI, PET, plasma etc.), we have adopted a multimodal approach to biomarker characterization. Because our center is particularly interested in multi-etiology dementia, the most common dementia in the normal aging population, we believe a multimodal approach to biomarkers will yield novel insights into the progression of such complex dementias. We propose to measure blood- and CSF-based biomarkers for AD, cerebral small vessel disease (cSVD), large-vessel ischemic disease, and inflammation. In addition, we will perform state-of-the-art MRI imaging incorporating biomarkers of AD, cSVD and neuroinflammation. We will also explore the utility of wearable devices to collect digital biomarkers tracking sleep and physical activity, especially given that Lewy body pathology can lead to early sleep disturbances. Finally, digital gait assessment will provide physical biomarkers of gait, which has been shown to decline early in individuals with cSVD and Lewy body dementia. Importantly, the Biomarker Core has been established for several years and is fully integrated within the UK-ADRC, working closely with the other cores to maximize the utility of the biomarker data collected to date. We will continue to support internal and external research projects on biomarkers, and will also contribute significantly to national and international consortium efforts to develop clinic-ready biomarkers for AD, VCID, and other underlying causes of dementia. Our specific aims are: Aim 1: Collect bi-annual blood-based biomarkers of AD, cSVD, large vessel disease, and inflammation. Aim 2: Collect baseline MRI scans and accompanying CSF ATN biomarkers on all cognitively normal participants in the longitudinal cohort. Aim 3: Fully characterize biomarkers on all participants at their clinical transition from cognitively normal / preMCI to MCI, and from MCI to dementia. Aim 4: Determine the utility of digital biomarkers including activity, sleep, and gait, in predicting cognitive decline and / or brain pathology. Aim 5: Contribute to national efforts to establish, harmonize, and standardize biomarkers including NACC, ADNI, and NCRAD. Aim 6: Integrate with the other cores of the UK-ADRC.

项目摘要/摘要：生物标志物核心 英国 ADRC 的主题是从正常到晚年多病因痴呆的转变，以及 生物标志物核心旨在提供数据并支持开发生物标志物谱的努力 可能导致个人认知能力下降的潜在病理。生物标记核心将提供 我们的队列在认知正常状态下的关键特征，并通过他们的认知 过渡。随着痴呆领域识别出潜在的疾病，生物标志物的用途正在迅速扩大。 修改疗法。我们不是专注于单一生物标志物模式（即 MRI、PET、血浆等），而是 采用了多模式方法来表征生物标志物。因为我们中心特别 对多病因痴呆症（正常老龄化人群中最常见的痴呆症）感兴趣，我们相信 生物标志物的多模式方法将为此类复杂痴呆症的进展提供新的见解。 我们建议测量基于血液和脑脊液的 AD、脑小血管疾病 (cSVD)、 大血管缺血性疾病和炎症。此外，我们将进行最先进的 MRI 成像 结合 AD、CVD 和神经炎症的生物标志物。我们还将探索可穿戴设备的实用性 收集跟踪睡眠和身体活动的数字生物标记的设备，特别是考虑到路易体 病理学可能导致早期睡眠障碍。最后，数字步态评估将提供物理生物标记 步态已被证明在患有 SVD 和路易体痴呆症的个体中早期会下降。重要的是， 生物标记核心已经建立多年，并完全整合到 UK-ADRC 内， 与其他核心密切合作，最大限度地利用迄今为止收集的生物标志物数据。我们将 继续支持内部和外部生物标志物研究项目，也将做出重大贡献 致力于为 AD、VCID 和其他药物开发临床就绪生物标志物的国家和国际联盟的努力 痴呆症的根本原因。我们的具体目标是： 目标 1：每年收集 AD、cSVD、大血管疾病和炎症的血液生物标志物。 目标 2：收集所有认知正常的基线 MRI 扫描和随附的 CSF ATN 生物标志物 纵向队列的参与者。 目标 3：全面表征所有参与者从认知正常/认知转变的临床转变过程中的生物标志物 preMCI 到 MCI，以及从 MCI 到痴呆。 目标 4：确定数字生物标记（包括活动、睡眠和步态）在预测认知方面的效用 衰退和/或脑部病理。 目标 5：为国家努力建立、协调和标准化生物标志物做出贡献，包括 NACC、 ADNI 和 NCRAD。 目标 6：与 UK-ADRC 的其他核心整合。