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期多性痴呆症的过渡，以及 生物标志物核心是提供数据和支持工作，以开发用于频谱的生物标志物概况 可能导致个人认知能力下降的基本病理。生物标志物核心将提供 我们在认知正常状态和通过认知的批判性表征 过渡。由于痴呆症领域确定了潜在的疾病 - 修改疗法。我们没有专注于单个生物标志物方式（即MRI，PET，等离子体等），而是我们 已经采用了多模式的生物标志物表征。因为我们的中心尤其是 对多性痴呆症感兴趣，这是正常衰老人群中最常见的痴呆症，我们认为 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。 我们建议测量用于AD，脑小血管疾病（CSVD）的基于血液和CSF的生物标志物， 大周围缺血性疾病和炎症。此外，我们将执行最新的MRI成像 结合AD，CSVD和神经炎症的生物标志物。我们还将探索可穿戴的实用性 收集数字生物标志物追踪睡眠和体育锻炼的设备，特别是考虑到Lewy身体 病理可能导致早期睡眠障碍。最后，数字收集评估将提供物理生物标志物 步态，该步态已显示出在CSVD和Lewy身体痴呆症患者的早期下降。重要的是， 生物标志物核心已经建立了几年，并且已完全集成在英国-ADRC中， 与其他核心紧密合作，以最大化迄今为止收集的生物标志物数据的实用性。我们将 继续支持有关生物标志物的内部和外部研究项目，也将做出重大贡献 向国家和国际财团的努力开发用于AD，VCID和其他的诊所就绪的生物标志物 痴呆症的根本原因。我们的具体目的是： AIM 1：收集AD，CSVD，大血管疾病和炎症的双重血液生物标志物。 目标2：收集基线MRI扫描并参与所有认知正常的CSF ATN生物标志物 纵向队列的参与者。 AIM 3：完全表征所有参与者的生物标志物，从认知正常 / Premci到MCI，从MCI到痴呆症。 目标4：确定数字生物标志物的实用性，包括活动，睡眠和聚集，预测认知 衰落和 /或大脑病理学。 AIM 5：为建立，协调和标准化NACC在内的国家努力做出贡献，包括NACC， Adni和Ncrad。 AIM 6：与英国-ADRC的其他核心集成。