Background and ObjectivesFish intake may prevent cerebrovascular disease (CVD), yet the mechanisms are unclear, especially regarding its impact on subclinical damage. Assuming that fish may have pleiotropic effect on cerebrovascular health, we investigated the association of fish intake with global CVD burden based on brain MRI markers.MethodsThis cross-sectional analysis included participants from the Three-City Dijon population-based cohort (age ≥65 years) without dementia, stroke, or history of hospitalized cardiovascular disease who underwent brain MRI with automated assessment of white matter hyperintensities, visual detection of covert infarcts, and grading of dilated perivascular spaces. Fish intake was assessed through a frequency questionnaire, and the primary outcome measure was defined as the first component of a factor analysis of mixed data applied to MRI markers. The association of fish intake with the CVD burden indicator was studied with linear regressions.ResultsIn total, 1,623 participants (mean age 72.3 years, 63% women) were included. The first component of factor analysis (32.4% of explained variance) was associated with higher levels of all 3 MRI markers. Higher fish intake was associated with lower CVD burden. In a model adjusted for total intracranial volume, compared to participants consuming fish <1 time per week, those consuming fish 2 to 3 and ≥4 times per week had a β = −0.19 (95% confidence interval −0.37 to −0.01) and β = −0.30 (−0.57 to −0.03) lower indicator of CVD burden, respectively (p trend < 0.001). We found evidence of effect modification by age such that the association of fish to CVD was stronger in younger participants (65–69 years) and not significant in participants ≥75 years of age. For comparison, in the younger age group, consuming fish 2 to 3 times a week was roughly equivalent (in the opposite direction) to the effect of hypertension.DiscussionIn this large population-based study, higher frequency of fish intake was associated with lower CVD burden, especially among participants <75 years of age, suggesting a beneficial effect on brain vascular health before manifestation of overt brain disease.Classification of EvidenceThis study provides Class II evidence that in individuals without stroke or dementia, higher fish intake is associated with lower subclinical CVD on MRI.