The connection between cerebrovascular health and cognition has been of empirical interest to scientists for over a century. In 1894, Swiss neurologist, Otto Binswanger, described an association between postmortem cerebrovascular changes, including atherosclerosis, and cognitive impairment preceding death in middle-aged and older adults.1 One-hundred and twenty years later, the field has evolved beyond Binswanger’s seminal work to include midlife systemic vascular health factors as potential mechanistic drivers in abnormal cognitive aging, including the most common form of dementia, Alzheimer's disease.2,3 Article see p 1560 In this issue of Circulation , Yaffe and colleagues push the envelope further by reporting that longitudinal exposure to one or more vascular risk factors in early and midadulthood is associated with worse midlife cognitive performance.4 Participants from the Coronary Artery Risk Development in Young Adults (CARDIA) Study who were 18 to 30 years of age at baseline underwent vascular risk factor assessments every 2 to 5 years over a 25-year period. Cognitive assessment, conducted at the end of the follow-up period, included delayed episodic memory (Rey Auditory Verbal Learning Test), information processing speed (Digit Symbol Coding), and 1 key aspect of executive functioning (inhibition assessed by the Stroop Test). In unadjusted models, cumulative exposure of each vascular risk factor (with the exception of total cholesterol) was individually associated with poorer performance on all 3 cognitive measures at midlife. However, in models adjusting for or excluding participants with incident cardiovascular events (eg, myocardial infarction, coronary revascularization, congestive heart failure), findings were less consistent, and the significant effects that remained were diminished. Normal levels of each risk factor (defined by American Heart Association guidelines)5 were unrelated to midlife cognitive performance …