AbstractBackgroundCerebrovascular reactivity (CVR) to increased carbon dioxide (CO2) reflects cerebral microvascular function and is impaired in hypertension and stroke. Limited studies have looked at its relationship with cognitive performance in African Americans and Whites.MethodsWe used data from the Brain‐Stress Hypertension and Aging Program cohort (B‐SHARP) consisting of racially diverse individuals with normal cognition or mild cognitive impairment (MCI). CVR was measured using advanced signal modeling approach developed by BH/IH during blood oxygenation level dependent (BOLD) resting state ‐fMRI. Participants underwent cognitive assessment using global and domain‐specific tests such as Montreal Cognitive Assessment (MoCA), Boston Naming Test (BNT), Hopkins Verbal Learning Test‐Revised (HVLT‐R), and Trail Making Test. We used multivariate regression models to assess the relationship of CVR and cognitive domains and tested interaction of CVR with race.ResultsSuccessful CVR data were completed on 219 participants with mean age= 65.3 years (SD 7.8), 46% African American and 65% women. An increased resting whole brain CVR was associated with a higher MoCA score (β = 6.46, SE 2.43, p‐value 0.008), higher BNT score (β =2.15, SE 0.93 p‐value 0.02), and shorter time on Trail B‐A, (β= ‐113.4, SE 42.0, p‐value 0.007) after adjusting for mean arterial pressure. After adjusting for age, sex, and race, increased resting whole brain CVR was associated with higher MoCA (β =4.4, SE 2.26, p‐value 0.05), BNT score (β =1.46, SE 0.89, p‐value 0.1) and Trail B‐A score (β =‐86.7, SE 40.3, p‐value 0.03). There was no association with delayed memory based on HVLT‐R. The results were similar for individuals with normal cognition or MCI. There was a significant interaction by race (p<0.01) such that whole brain CVR was associated with better performance on all cognitive tests for African Americans but not for Whites.ConclusionsHigher CVR, reflected by resting state BOLD‐fMRI, was associated with higher overall cognitive status and specific domains including language and executive functioning in individuals with normal cognition or MCI. The differential effect in African Americans vs Whites could suggest a greater contribution of microvascular dysfunction for the higher prevalence of cognitive impairment in African Americans.