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: 10459471
• 负责人: Donna M Wilcock
• 金额: $ 59.48万
• 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/10459471
• 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.

项目概要/摘要：生物标志物核心 我们UK-ADRC的主题是从正常到晚年多病因痴呆的转变，以及 生物标志物核心是提供数据和支持努力，以开发生物标志物谱的光谱， 可能导致个体认知能力下降的潜在病理。生物标志物核心将提供 在他们的认知正常状态下，我们的队列的关键特征，并通过他们的认知 过渡。生物标志物的用途正在迅速扩大，因为痴呆症领域可以识别潜在的疾病- 改良疗法而不是专注于单一生物标志物模态（即MRI、PET、血浆等），我们 采用了多模式方法来表征生物标志物。因为我们的中心 对多病因痴呆症感兴趣，这是正常老年人群中最常见的痴呆症，我们相信， 生物标志物的多模式方法将对这种复杂痴呆的进展产生新的见解。 我们建议测量AD、脑小血管疾病（cSVD）、 大血管缺血性疾病和炎症。另外，我们会进行最先进的核磁共振成像 整合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实用性， 收集跟踪睡眠和身体活动的数字生物标志物的设备，特别是考虑到路易体 病理学会导致早期睡眠障碍。最后，数字步态评估将提供物理生物标志物 步态，这已被证明是下降的早期与cSVD和路易体痴呆的个人。重要的是， 生物标志物核心已经建立了几年，并完全整合在UK-ADRC中， 与其他核心密切合作，以最大限度地利用迄今为止收集的生物标志物数据。我们将 继续支持生物标志物的内部和外部研究项目， 国家和国际财团努力开发AD，VCID和其他临床可用的生物标志物， 痴呆症的根本原因我们的具体目标是： 目的1：收集AD、cSVD、大血管疾病和炎症的两年一度血液生物标志物。 目的2：收集所有认知正常的患者的基线MRI扫描和伴随的CSF ATN生物标志物 纵向队列的参与者。 目标3：充分表征所有参与者在从认知正常/认知障碍的临床过渡期的生物标志物。 从MCI到MCI，从MCI到痴呆。 目的4：确定数字生物标志物（包括活动、睡眠和步态）在预测认知功能方面的效用。 衰退和/或脑病理学。 目标5：促进国家努力建立、协调和标准化生物标志物，包括NACC， ADNI和NCRAD。 目标6：与UK-ADRC的其他核心集成。