Cognitive impairment and dementia (CID) are major public health problems with substantial personal, social, and financial burdens. African Americans are at a heightened risk for Vascular Cognitive Impairment (VCI) compared to European Americans. Recent lines of evidence also suggest a high burden of Post-stroke VCI among indigenous Africans. A better understanding of the cause(s) of the racial disparity in CID, specifically VCI, is needed in order to develop strategies to reduce it. We propose and discuss the conceptual framework for a unique tri-population, trans-continental study titled The Vascular brain Injury Progression after Stroke (VIPS) study. The overarching objective of the VIPS Study will be to explore the interplay of multiple factors (racial, geographical, vascular, lifestyle, nutritional, psychosocial and inflammatory) influencing the level and trajectory of post-stroke cognitive outcomes and examine whether differences between indigenous Africans, African Americans and European Americans exist. We hypothesize that differences which might be due to racial factors will be observed in African Americans versus European Americans as well as Indigenous Africans versus European Americans but not in African Americans versus Indigenous Americans; differences due to geographical factors will be observed in Indigenous Americans versus African Americans and Indigenous Africans versus European Americans but not in African Americans versus European Americans. This overarching objective could be accomplished by building upon existing National Institutes of Health investments in the REasons for Geographical And Racial Differences in Stroke (REGARDS) study (based in the United States of America) and the Stroke Investigative Research and educational Network (SIREN) study (based in Sub-Saharan Africa).