Cardiovascular Risk Factors Have Different Effects on Total Brain Volume and Cerebral White Matter Lesions Over Time: The Helius Study

Objective: Cardiovascular risk factors have been associated with brain volume reduction and the development of cerebral white matter lesions (WML), both early markers of cognitive decline and cerebrovascular disease. Most studies, however, are cross-sectional in design and involve older populations. We examined the prognostic value of cardiovascular risk factors on brain and WML volumes in a middle-aged, multi-ethnic population. Design and method: We use baseline data and 3T brain magnetic resonance imaging (MRI) scans in 562 participants of Moroccan, South-Asian Surinamese, and Dutch descent from the HELIUS study. Brain volume and WML volumes were determined using automated segmentation pipelines based on MP-RAGE and 3D-FLAIR scans. Linear regression analyses, adjusted for age, sex, and ethnicity, were performed to assess the association between (change in) cardiovascular risk factors and brain and WML volumes. Results: Mean age was 58.5 (standard deviation 7.7) years, 45% was female. Median follow-up time was 8.4 [interquartile range 7.4; 9.5] years. Both elevated BMI and presence of diabetes at baseline as well as increases in BMI and HbA1C levels over time were significantly associated with reduced brain volume at follow-up. Hypertension, systolic and diastolic blood pressure levels, the use of antihypertensive medication, new-onset hypertension and history of cerebrovascular disease were all independently and positively associated with WML volume. Conclusions: Elevated body weight and diabetes mellitus significantly contribute to decreased brain volumes, whereas hypertension and cerebrovascular disease are key risk factors for the development of WML. The present findings underscore the importance of obesity and hypertension in mid-life as predictors of future risk of cerebrovascular disease.