Background: When clustered together, risk factors for cardiovascular disease, stroke, and type 2 diabetes mellitus (e.g., hypertension and dyslipidemia) are called metabolic syndrome (MetS).1 In the Canadian Health Measures Survey, 21% of Canadians between the ages of 18 and 79 were classified as having MetS2 while the prevalence in the European population is about one-quarter.3 With the rising worldwide prevalence of MetS, it is important to determine the extent to which MetS affects cerebrovascular health. In addition, apolipoprotein E (APOE) plays a role in lipid metabolism as it serves as a transport molecule of triglyceride-rich particles and high density lipoprotein cholesterol.4 Since MetS is associated with an imbalance in lipid and lipoprotein metabolism, the role of the APOE genotype may be associated with MetS and cerebrovascular outcomes. The purpose of this study was to examine the effect of MetS on cerebrovascular health indices in healthy older adults and determine the influence of apolipoprotein E (APOE) ε4 expression. Methods: Participants included 258 healthy, sedentary older adults (122 men, 136 postmenopausal women) aged 54 to 93 yrs (65.9±6.3 yrs, mean±SD), who volunteered for a longitudinal exercise intervention study titled the Brain in Motion study.5 In a cross-sectional study of baseline, pre-intervention, data we investigated the association between cerebrovascular health indices, MetS, and APOE genotype. MetS was determined using standard diagnostic criteria.1 APOE genotyping was conducted on 242 samples and sequence data were generated using PCR-amplification followed by Sanger sequencing. Seventy-seven participants (29.8%) met criteria for MetS. To model the association between cerebrovascular outcomes and MetS after controlling for APOE genotype, age, sex, education, and behavioural outcomes, ordinary linear regression analysis based on M-estimator was used. Results: Compared to participants without MetS, participants with MetS had lower resting cerebral blood flow (CBF) peak velocity (P) p<0.01, cerebrovascular conductance (CVC) p<0.0001, P-reactivity (change in P divided by the change in PETCO2 from +1 mmHg to +8 mmHg) p=0.03, and CVC-reactivity (change in CVC divided by the change in PETCO2) p=0.01. APOE ε4 carriers had higher CVC (p=0.03) and P-reactivity (p=0.037) than non-carriers. Conclusion: These results provide evidence that after adjusting for sociodemographic & lifestyle factors and APOE genotype, cardiometabolic risk factors clustered together as MetS predict cerebrovascular health indices in older adults. Furthermore, APOE ε4 carrier had higher CVC and P-reactivity, suggesting that compensatory mechanisms to protect the vulnerable brain may underlie the associations between cerebrovascular health and APOE genotype.