MarkVCID Validation in the General Community

普通社区中的 MarkVCID 验证

• 批准号: 10364014
• 负责人: RONALD C PETERSEN
• 金额: $ 245.42万
• 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 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10364014
• 关键词: Address; African American; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease related dementia; Amyloid; Biological Markers; Blood Vessels; Cardiovascular system; Caucasians; Cerebral small vessel disease; Clinic; Clinical; Clinical Trials; Cognition; Cognitive; Cohort Studies; Communities; DNA; Data; Data Collection; Dementia; Diffuse; Disease Marker; Electronic Health Record; Elements; Endothelium; Epidemiology; Evaluation; Florida; Funding Opportunities; Future; Goals; Grant; Growth; Health; Hispanics; Image; Impaired cognition; Incidence; Individual; Light; Liquid substance; Longitudinal Studies; Magnetic Resonance Imaging; Measurement; Measures; Medical History; Medical center; Metabolic; Microvascular Dysfunction; Mississippi; Participant; Pathology; Patient Recruitments; Performance; Phase; Phenotype; Pittsburgh Compound-B; Plasma; Population; Population Heterogeneity; Population Study; Positron-Emission Tomography; Race; Resources; Risk; Risk Factors; Sampling; Signal Transduction; Site; Skeleton; Standardization; Structure; Surrogate Endpoint; United States National Institutes of Health; Universities; Validation; Vascular Cognitive Impairment; Water; White Matter Hyperintensity; Work; base; biomarker development; biomarker validation; clinical biomarkers; clinical care; clinical examination; clinical practice; clinical research site; cognitive testing; cohort; follow-up; imaging biomarker; in vivo; innovation; insight; mild cognitive impairment; neurofilament; neuroimaging; phenotypic biomarker; population based; recruit; research clinical testing; screening; sex; tau Proteins; vascular cognitive impairment and dementia

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 脑小血管病 (SVD) 是一种导致认知障碍的常见病理，并降低了阿尔茨海默病存在时痴呆的表达阈值，而人群中阿尔茨海默病相关痴呆 (AD/ADRD) 联盟是由 MarkVCID 联盟建立的。 NIH 的目标是识别和验证 SVD 生物标志物，帮助捕获血管对认知障碍和痴呆 (VCID) 的影响，MarkVCID 联盟正朝着高质量生物标志物的全面多中心临床验证迈进。到目前为止，我们组建的团队汇集了成功验证网站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，我们将重点招募 200 名参与者 (120 名) 组成的多元化群体。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) 的白种人、40 名非裔美国人、40 名西班牙裔人 我们将招募具有以下风险的不同群体的参与者。 VCID 使用创新的两步筛选方法，我们应用程序的一个关键优势是从 Mayo Clinic 老龄化研究 (MCSA) 招募 MCR 参与者，其中来自超过 30 项纵向研究的遗留资源（临床、影像、电子健康记录）。将利用 3000 名活跃参与者来丰富参与者群体，并允许我们在这些参与者的丰富数据和 AD 生物标记物设置中评估拟议的 MarkVCID 生物标记物的相关性和重要性。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、种族的函数。这些分析将使我们能够更好地了解每个 SVD 标记在临床目的中的效用，我们将利用现有的 MCSA 成像数据（FLAIR 和 DTI MRI）。 MRI 和临床随访可计算 MarkVCID 成像生物标志物，并使用淀粉样蛋白和 tau PET 评估其在预测纵向结构 MRI 和认知能力下降方面的临床有效性。这种对 MCSA 中成像生物标志物的独立验证对于提供 MarkVCID 生物标志物和认知衰退的机制见解非常重要。评估它们在基于人群的样本中的临床效用。