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: 10261967
• 负责人: Donna M Wilcock
• 金额: $ 62.46万
• 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/10261967
• 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; Clinic; Clinical; Cognitive; Collection; Complex; Consensus; Data; Dementia; Disease; Elderly; Etiology; Gait; Goals; Image; Impaired cognition; Individual; Inflammation; International; Kentucky; Lead; 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; base; biomarker development; biomarker performance; blood-based biomarker; 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 我们英国-ADRC的主题是从正常到晚年多病因痴呆的过渡，以及 Biomarker Core将提供数据并支持开发生物标记物图谱的努力 可能导致个人认知能力下降的潜在病理因素。Biomarker核心将提供 在他们认知正常的状态下，通过他们的认知，对我们的队列进行批判性表征 过渡。随着痴呆症领域识别潜在的疾病，生物标记物的用途正在迅速扩大。 修改治疗方法。我们不是专注于单一的生物标志物模式(即MRI、PET、血浆等)，而是 已经采用了多模式方法来表征生物标记物。因为我们的中心特别是 对多病因痴呆症感兴趣，这是正常老龄化人口中最常见的痴呆症，我们认为 对生物标记物的多模式方法将为此类复杂痴呆的进展提供新的见解。 我们建议测量基于血液和脑脊液的生物标记物，用于AD、脑小血管疾病(CSVD)、 大血管缺血性疾病和炎症。此外，我们还将进行最先进的核磁共振成像 合并AD、cSVD和神经炎症的生物标志物。我们还将探索可穿戴设备的用途 收集跟踪睡眠和体力活动的数字生物标记物的设备，特别是考虑到路易体 病理可能会导致过早的睡眠障碍。最后，数字步态评估将提供物理生物标记物 步态，这已被证明在cSVD和路易体痴呆症患者中早期下降。重要的是 Biomarker Core已经建立了几年，并完全整合到英国-ADRC， 与其他岩心密切合作，最大限度地利用迄今收集的生物标志物数据。我们会 继续支持有关生物标志物的内部和外部研究项目，并将作出重大贡献 为国内和国际财团努力为AD、VCID和其他疾病开发临床可用的生物标记物 痴呆症的根本原因。我们的具体目标是： 目的1：每两年收集一次AD、cSVD、大血管疾病和炎症的血液生物标志物。 目的2：收集所有认知正常的基线MRI扫描和伴随的脑脊液ATN生物标志物 纵向队列中的参与者。 目标3：充分描述所有参与者从认知正常/临床过渡的生物标记物 前MCI到MCI，从MCI到痴呆。 目的4：确定包括活动、睡眠和步态在内的数字生物标记物在预测认知方面的效用 衰退和/或脑部病理。 目标5：促进建立、协调和标准化包括NACC在内的生物标记物的国家努力， ADNI和NCRAD。 目标6：与英国-ADRC的其他核心整合。