MarkVCID Validation in the General Community

项目总结/摘要 脑小血管病（SVD）是一种常见的病理学，有助于认知障碍，并降低了阿尔茨海默病和阿尔茨海默病相关痴呆（AD/ADRD）人群中痴呆的表达阈值。MarkVCID联盟由NIH建立，目标是鉴定和验证SVD生物标志物，帮助捕获血管对认知障碍和痴呆（VCID）的贡献。随着MarkVCID联盟向迄今为止确定的高质量生物标志物的全面多中心临床验证迈进，我们的团队汇集了成功验证网站所需的专业知识和资源，作为此次资助机会公告的一部分（RFA- NS-21-005）。我们将专注于在马约诊所罗切斯特（MCR）、密西西比大学医学中心（UMMC）和马约诊所佛罗里达（MCF）招募200名参与者（120名白人、40名非洲裔美国人、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。我们申请的一个关键优势是从马约诊所老龄化研究（MCSA）招募MCR参与者，（临床，成像，电子健康记录）将利用来自3000多名活跃参与者的纵向研究的数据来丰富参与者队列，并使我们能够在丰富的数据和AD背景下评估拟议MarkVCID生物标志物的相关性和重要性。这些参与者身上的生物标志物。在这项资助中，我们将专注于收集数据，用于评估和比较两种血浆和四种基于MRI的MarkVCID生物标志物。在目标1中收集数据后，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标志物在临床上的效用。在目标3中，我们将利用现有的MCSA成像数据（FLAIR和DTI MRI）以及系列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和认知下降方面的临床有用性。MCSA中成像生物标志物的这种独立验证对于提供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将是重要的。

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.