PROJECT SUMMARY Vascular contributions to cognitive impairment and dementia (VCID) are the second leading cause of dementia, and a major contributor to Alzheimer’s disease (AD), the most common cause of dementia. Non- invasive biomarkers are critical for the development of prevention and treatment strategies for VCID. The first grant cycle of the MarkVCID consortium identified 11 candidate imaging and fluid biomarkers. In this second grant cycle (RFA-NS-21-005), the VCID consortium will “…carry out comprehensive multi-site clinical validation of up to six of these 11 biomarkers….” In response to this RFA, a strong partnership between Washington University School of Medicine and the University of Texas, Southwestern Medical Center (WU-UTSW) has been developed to serve as a new site for the Small Vessel VCID Consortium. Both institutions are high-volume tertiary care referral centers that serve large metropolitan areas with racial, ethnic, socioeconomic, and urban/rural diversity. St. Louis and Dallas are located within or adjacent to the stroke belt—with significant portions of the population at the highest risk of stroke, cerebrovascular disease, and VCID. Because VCID sits at the interface between cerebrovascular risk and age-related dementia, this partnership leverages strengths in both the cerebrovascular and Alzheimer’s disease (AD) research infrastructures that already exist at WU and UTSW. Both Institutions have active AD research centers, and WU is a StrokeNet regional coordinating center, demonstrating a strong track record of collaborative network-based clinical studies. In addition, investigators from both centers are actively leading several independent longitudinal clinical studies that involve participants with VCID or ADRD. We have assembled a group of stroke and AD clinicians, clinical investigators, and scientists who have diverse expertise in VCID and AD pathobiology, clinical trials implementation and management, fluid biomarker collection and measurement, MR image acquisition and processing, informatics and data sharing, and statistics. The collective expertise of the WU-UTSW group will not only permit the implementation of the current VCID biomarker study but will also provide unique proficiencies in refining the design of the current and future biomarker studies for VCID. We will achieve the goals of the VCID consortium through the following aims: Aim 1: Recruit and longitudinally follow a diverse cohort of participants at risk for VCID. Aim 2: Longitudinally acquire and reproducibly measure fluid-based biomarkers for this VCID cohort. Aim 3: Longitudinally acquire and reproducibly process MRI-based biomarkers for the VCID cohort.