MarkVCID Validation in the General Community

项目摘要/摘要

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.