Associations between adiposity and white matter hyperintensities: Cross-sectional and longitudinal analyses of 34,653 participants

ObjectivesWhite matter hyperintensities (WMH) increase the risk of stroke and cognitive impairment. This study aims to determine the cross-sectional and longitudinal associations between adiposity and WMH.MethodsParticipants were enrolled from the UK Biobank cohort. Associations of concurrent, past, and changes in overall and central adiposity with WMH were investigated by linear and nonlinear regression models. The association of longitudinal adiposity and WMH volume changes was determined by a linear mixed model. Mediation analysis investigated the potential mediating effect of blood pressure.ResultsIn 34,653 participants with available adiposity measures and imaging data, the concurrent obese group had a 25.3% (beta [95% CI] = 0.253 [0.222-0.284]) higher WMH volume than the ideal weight group. Increment in all adiposity measures was associated with a higher WMH volume. Among them, waist circumference demonstrated the strongest effect (beta [95% CI] = 0.113 [0.101-0.125]). Past adiposity also demonstrated similar effects. Among the subset of 2664 participants with available WMH follow-up data, adiposity measures were predictive of WMH change. Regarding changes of adiposity, compared with ideal weight stable group, those who turned from ideal weight to overweight/obese had a 8.1% higher WMH volume (beta [95% CI] = 0.081 [0.039-0.123]), while participants who turned from overweight/obese to ideal weight demonstrated no significant WMH volume change. Blood pressure partly meditates the associations between adiposity and WMH.ConclusionsBoth concurrent and past adiposity were associated with a higher WMH volume. The detrimental effects of adiposity on WMH occurred throughout midlife and in the elderly and may still exist after changes in obesity status. After selection of included participants and clarification of the time points of these participants, we studied the linear and non-linear association between adiposity measures and WMH. Sensitivity analysis was conducted by stratification of sex, age, and follow-up duration. Then, we explored the possible mediator for association between adiposity and WMH.image