Background: Because cardiovascular (CV) risk factors have been associated with declines in cognitive functions and late life dementia, CV risk factors should also be associated with brain atrophy. Objective: To study the association of CV risk factors with ventricular size (VS) and sulcal size (SS) in the middle-aged and young-elderly Atherosclerosis Risk in Communities (ARIC) Study cohort. Methods: Cerebral MRI was performed on 1,812 individuals (aged 50 to 73 mean 62.3 -years, 60%women, 50%African American) with no history of stroke or TIA from the ARIC cohort at study sites in Forsyth County, NC, and Jackson, MS. Neuroradiologists rated VS and SS using a semiquantitative, 10-point scale by visual comparison with a standardized reference atlas. CV risk factors were assessed approximately 6 years prior to the MR scan. The authors performed multivariate analyses to assess the independent relationship between CV risk factors and the two measures of brain atrophy. Results: Logistic regression models controlling for age, sex, race, and alcohol use found that the association between diabetes and VS is as follows: OR = 1.63, 95%CI: 1.19 to 2.24; p = 0.003. Increasing levels of fasting blood glucose also showed an association with greater VS (OR = 1.07, 95%CI: 1.03 to 1.10; p = 0.001, for each 10 mg/dL of blood glucose). No other CV risk factors were associated with greater VS or SS. Conclusions: In this middle-aged and young-elderly cohort, diabetes mellitus was associated with greater ventricular size. Mechanisms for deterioration of brain structural integrity may include microvascular, amyloidogenic, or other not-yet-defined effects of diabetes mellitus. Background: Because cardiovascular (CV) risk factors have been associated with declines in cognitive functions and late life dementia, CV risk factors should also be associated with brain atrophy. Objective: To study the association of CV risk factors with ventricular size (VS) and sulcal size (SS) in the middle-aged and young-elderly Atherosclerosis Risk in Communities (ARIC) Study cohort. Methods: Cerebral MRI was performed on 1,812 individuals (aged 50 to 73 mean 62.3 -years, 60% women, 50% African American) with no history of stroke or TIA from the ARIC cohort at study sites in Forsyth County, NC, and Jackson, MS. Neuroradiologists rated VS and SS using a semiquantitative, 10-point scale by visual comparison with a standardized reference atlas. CV The risk factors were rate approximately 6 years prior to the MR scan. The authors performed multivariate analyzes to assess the independent relationship between CV risk factors and the two measures of brain atrophy. Results: Logistic regre ssion models controlling for age, sex, race, and alcohol use found that the association between diabetes and VS is as follows: OR = 1.63, 95% CI: 1.19 to 2.24; p = 0.003. Increasing levels of fasting blood glucose also showed an association with greater VS (OR = 1.07, 95% CI: 1.03 to 1.10; p = 0.001 for each 10 mg / dL of blood glucose). No other CV risk factors were associated with greater VS or SS. Conclusions: In this middle -aged and young-elderly cohort, diabetes mellitus was associated with greater ventricular size. Mechanisms for deterioration of brain structural integrity may include microvascular, amyloidogenic, or other not-yet-defined effects of diabetes mellitus.