Validation of Imaging and Blood-based Small Vessel VCID Biomarkers in Multiethnic Population

PROJECT SUMMARY/ABSTRACT The MarkVCID consortium was established in 2016 to pursue the initial stages of multi-site validation of 7 imaging-based and 4 fluid-based candidate biomarkers for small vessel vascular contributions to cognitive impairment and dementia (VCID). As one of the 7 participating sites, our team at the University of Southern California (USC) has analyzed and optimized candidate VCID biomarkers during the UH2 phase (years 1-2), and participated in the consortium-wide program of biomarker scaling-up, multi-site protocol implementation, and initial multi-site validation during the UH3 phase (years 3-5). USC has led the consortium wide development and implementation of the optical coherence tomography angiography (OCTA) biomarker kit which is based on an FDA approved device that allows in vivo and completely noninvasive imaging of retinal capillaries with a spatial resolution of ~10 microns. We have also participated in the validation of the other 6 MRI based candidate biomarkers, while contributing blood samples for the validation of the 3 plasma-based candidate biomarkers. The primary objective of the next 5 years is to carry out comprehensive multi-site clinical validation of candidate VCID biomarkers in longitudinal studies of diverse populations that are typical in clinical settings in the US. Capitalizing on the high racial diversity in Los Angeles, we plan to enroll a multiethnic longitudinal cohort of at least 200 subjects that are enriched for small vessel VCID, including 100 Latinx subjects from the Los Angeles Latino Eye Study (LALES), 50 African Americans (AAs) enrolled in the African American Eye Disease Study (AFEDS), and 50 Caucasian participants from the Clinical Core of the USC ADRC. We have performed pilot studies in both Latinx and AA subjects (two largest minority groups in the US) using MarkVCID protocols to show the feasibility for conducting such studies in a multiethnic cohort. We have also built a multiethnic team of investigators, technical staff, research coordinators, and community outreach staff to streamline enrollment, achieve the recruitment milestones and perform longitudinal follow-up studies. Our team includes established expertise, equipment and infrastructure for OCTA, MRI, fluid biomarker and clinical/cognitive evaluation of VCID, as well as a proven track record in the sharing of de-identified clinical data through the Laboratory of Neuro Imaging (LONI) for the second phase of MarkVCID project.