PROJECT SUMMARY/ABSTRACT Small vessel cerebrovascular disease is common in the elderly and is a well-known contributor to cognitive decline. A major gap in the field, however, is the ongoing need for reliable and reproducible biologic markers of vascular disease suitable for early detection, disease monitoring, and measuring treatment efficacy. The overarching goal of this proposal is to clinically validate novel neuroimaging and fluid-based biomarkers of a cerebrovascular disease selected by the NINDs and developed during the first five years of the MarkVCID consortium. We propose to longitudinally follow a cohort of 200 diverse, older subjects who present with a range of cerebrovascular burdens and cognitive complaints, and functional decline. Our aims are to validate the MarkVCID biomarkers and address possible interactions between these biomarkers and Alzheimer?s disease pathophysiology. Accomplishing these goals will improve the early detection, diagnosis, and prognosis of small vessel cerebrovascular disease in older subjects and provide better targets and outcome metrics for clinical trials.