MarkVCID Validation in the General Community

项目摘要/摘要 脑小血管病(SVD)是一种常见的认知损害的病理，它降低了阿尔茨海默病和阿尔茨海默病相关痴呆(AD/ADRD)人群中痴呆的表达门槛。MarkVCID联盟由美国国立卫生研究院建立，目标是识别和验证有助于捕捉认知障碍和痴呆(VCID)的血管贡献的SVD生物标记物。随着MarkVCID联盟迈向对迄今已确定的高质量生物标记物的全面多地点临床验证，我们组建的团队将成为成功验证地点所需的专业知识和资源汇聚在一起，作为此次融资机会公告的一部分(RFA-NS-21-005)。我们将专注于在梅奥诊所罗切斯特(MCR)、密西西比大学医学中心(UMMC)和佛罗里达梅奥诊所(MCF)招募200名参与者(120名高加索人，40名非洲裔美国人，40名西班牙裔美国人)。我们将使用创新的两步筛查方法招募有VCID风险的不同群体的参与者。我们的应用程序的一个关键优势是从Mayo Clinic Study of Aging(MCSA)招募MCR参与者，其中来自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)将被利用来丰富参与者队列，并使我们能够评估拟议的MarkVCID生物标记物在这些参与者的丰富数据和AD生物标记物设置中的相关性和重要性。在这笔赠款中，我们将重点收集数据，用于评估和比较两种血浆和四种基于MRI的MarkVCID生物标记物。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。这些分析将使我们更好地了解每个SVD标记物在临床上的用途。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，并评估它们与淀粉样蛋白和tau PET在预测纵向结构MRI和认知功能下降方面的临床应用价值。这种对MCSA中成像生物标记物的独立验证将对提供对MarkVCID生物标记物的机械性见解并在基于人群的样本中评估其临床应用具有重要意义。

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.