The purpose of this notice of funding opportunity (NOFO) is to support research designed to, in parallel in human-based and model-based studies, advance fundamental understanding of basic disease-related molecular mechanisms of vascular contributions to cognitive impairment and dementia (VCID). Specifically, this NOFO solicits applications focused on molecular mechanisms of small cerebral vessel diseases, including one or more of arteriolosclerosis, cerebral amyloid angiopathy (CAA), and atherosclerosis (direct impact or downstream effects on small vessels) that contribute to dementia diagnoses. Proposed research will use team-based and multi-faceted approaches to understand these small vessel disorders both cross-sectionally and over time (prodromal and after phenotypic disease first develops), as well as their relationship to VCID phenotypic and clinical outcomes. In addition to standard NIH sharing requirements, the program will highlight Center Without Walls (CWOW) sharing of pre-publication ideas, data, methods, and results. The overall goal is to generate, via a collaborative CWOW framework, foundational knowledge in the emerging field of VCID that is needed for future development of interventions including for prevention and better clinical outcomes.