MarkVCID Validation in the General Community

普通社区中的 MarkVCID 验证

• 批准号: 10619433
• 负责人: RONALD C PETERSEN
• 金额: $ 364.68万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-23 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10619433
• 关键词: MarkVCID; Validation; General; Community

PROJECT SUMMARY / ABSTRACT Cerebral small vessel disease (SVD) is a common pathology contributing to cognitive impairment and lowers the threshold for the expression of dementia in the presence of Alzheimer’s disease, and Alzheimer’s related dementias (AD/ADRD) in the population. MarkVCID consortium was established by the NIH with the goal of identifying and validating SVD biomarkers that help capture vascular contributions to cognitive impairment and dementia (VCID). As the MarkVCID consortium moves towards comprehensive multi-site clinical validation of high-quality biomarkers identified so far, our assembled team brings together the expertise and resources needed to be a successful validation site as part of this funding opportunity announcement (RFA- NS-21-005). We will focus on recruiting a diverse group of 200 participants (120 Caucasians, 40 African Americans, 40 Hispanics) at Mayo Clinic Rochester (MCR), University of Mississippi Medical Center (UMMC), and Mayo Clinic Florida (MCF). We will recruit a diverse group of participants at risk of VCID using an innovative two-step screening approach. A key strength of our application is the recruitment of participants at MCR from Mayo Clinic Study of Aging (MCSA) where legacy resources (clinical, imaging, electronic health records) from the longitudinal study of over 3000 active participants will be leveraged to enrich the cohort of participants as well as allow us to evaluate the relevance and importance of the proposed MarkVCID biomarkers in the setting of rich data and AD biomarkers on these participants. In this grant, we will focus on collecting data for the evaluation and comparison of two plasma and four MRI-based MarkVCID biomarkers. After the collection of data in Aim 1, Aim 2 will focus on evaluating and comparing these MarkVCID biomarkers as a function of age, sex, systemic vascular health, race, and cognitive trajectories. These analyses will allow us to better understand the utility of each of the SVD markers for clinical purposes. In Aim 3, we will utilize existing MCSA imaging data (FLAIR and DTI MRI) with serial MRI and clinical follow-up to compute MarkVCID imaging biomarkers and evaluate their clinical usefulness with amyloid and tau PET in predicting longitudinal structural MRI and cognitive decline. This independent validation of imaging biomarkers in MCSA will be important for providing mechanistic insights into the MarkVCID biomarkers and evaluating their clinical utility in a population-based sample.

项目概要/摘要 脑小血管疾病 (SVD) 是一种导致认知障碍的常见病理，并降低了人群中存在阿尔茨海默病和阿尔茨海默病相关痴呆 (AD/ADRD) 时表达痴呆的阈值。 MarkVCID 联盟由 NIH 建立，旨在识别和验证 SVD 生物标志物，帮助捕获血管对认知障碍和痴呆 (VCID) 的影响。随着 MarkVCID 联盟转向对迄今为止确定的高质量生物标志物进行全面的多站点临床验证，我们的组建团队汇集了成功验证站点所需的专业知识和资源，作为本次融资机会公告 (RFA-NS-21-005) 的一部分。我们将重点在罗切斯特梅奥诊所 (MCR)、密西西比大学医学中心 (UMMC) 和佛罗里达州梅奥诊所 (MCF) 招募 200 名不同的参与者（120 名白人、40 名非裔美国人、40 名西班牙裔）。我们将使用创新的两步筛选方法招募具有 VCID 风险的多元化参与者。我们应用程序的一个关键优势是从 Mayo Clinic 衰老研究 (MCSA) 招募 MCR 参与者，其中将利用来自 3000 多名活跃参与者的纵向研究的遗留资源（临床、影像、电子健康记录）来丰富参与者群体，并允许我们评估拟议的 MarkVCID 生物标志物在丰富数据和 AD 生物标志物设置中的相关性和重要性。 参与者。在这笔资助中，我们将重点收集用于评估和比较两种血浆和四种基于 MRI 的 MarkVCID 生物标志物的数据。目标 1 收集数据后，目标 2 将重点评估和比较这些 MarkVCID 生物标志物作为年龄、性别、全身血管健康、种族和认知轨迹的函数。这些分析将使我们能够更好地了解每种 SVD 标记物在临床上的效用。在目标 3 中，我们将利用现有的 MCSA 成像数据（FLAIR 和 DTI MRI）以及连续 MRI 和临床随访来计算 MarkVCID 成像生物标志物，并评估其与淀粉样蛋白和 tau PET 在预测纵向结构 MRI 和认知能力下降方面的临床有效性。 MCSA 中成像生物标志物的独立验证对于提供 MarkVCID 生物标志物的机制见解并评估其在基于人群的样本中的临床效用非常重要。