Prevalence of Alzheimer’s disease (AD) will reach epidemic proportions in the United States and worldwide in the coming decades, and with substantially higher rates in African Americans (AAs) than in Whites. Older age, family history, low levels of education, and ɛ4 allele of the apolipoprotein E (APOE) gene are recognized risk factors for the neurodegeneration in AD and related disorders. In AAs, the contributions of APOE gene to AD risk continue to engender a considerable debate. In addition to the established role of cardiovascular disease (CVD) risk in vascular dementia, it is now believed that CVD risk and its endophenotype may directly comediate AD phenotype. Given the pleiotropic effects of APOE on CVD and AD risks, the higher rates of CVD risks in AAs than in Whites, it is likely that CVD risks contribute to the disproportionately higher rates of AD in AAs. Though the advantageous effects of aerobic exercise on cognition is increasingly recognized, this evidence is hardly definitive, and data on AAs is lacking. In this paper, we will discuss the roles of CVD risk factors in the development of AD and related dementias, the susceptibility of these risk factors to physiologic adaptation, and fitness-related improvements in cognitive function. Its relevance to AD prevention in AAs is emphasized.