Previous studies have shown that socioeconomically deprived groups exhibit higher lesion load of the white matter (WM) in aging. The aim of this study was to (i) investigate to what extent education and income may contribute to differences in white matter hyperintensities (WMHs) and (ii) identify risk profiles related to a higher prevalence of age-associated WMH.

Population-based adult study of the Leipzig Research Centre for Civilization Diseases (LIFE) in Leipzig, Germany.

Dementia-free sample aged 40–80 years (n = 1,185) derived from the population registry.

Information was obtained in standardized interviews. WMH (including the derived Fazekas scores) were assessed using automated segmentation of high-resolution T1-weighted anatomical and fluid-attenuated inversion recovery (FLAIR) MRI acquired at 3T.

Despite a significant association between income and WMH in univariate analyses, results from adjusted models (age, gender, arterial hypertension, heart disease, and APOE e4 allele) indicated no association between income and WMH. Education was associated with Fazekas scores, but not with WMH and not after Bonferroni correction. Prevalence of some health-related risk factors was significantly higher among low-income/education groups. After combining risk factors in a factor analysis, results from adjusted models indicated significant associations between higher distress and more WMH as well as between obesity and more deep WMH.

Previously observed differences in WMH between socioeconomically deprived groups might stem from differences in health-related risk factors. These risk factors should be targeted in prevention programs tailored to socioeconomically deprived individuals.

Cumulative burden from vascular risk factors (VRFs) has been associated with an increased risk of depressive symptoms in mid- and later life. It has been hypothesised that this association arises because VRFs disconnect fronto-subcortical white matter tracts involved in mood regulation, which puts older adults at higher risk of developing depressive symptoms. However, evidence for the hypothesis that disconnection of white matter tracts underlies the association between VRF burden and depressive symptoms from longitudinal studies is scarce.

This preregistered study analysed longitudinal data from 6,964 middle-aged and older adults from the UK Biobank who participated in consecutive assessments of VRFs, brain imaging, and depressive symptoms. Using mediation modelling, we directly tested to what extend white matter microstructure mediates the longitudinal association between VRF burden and depressive symptoms.

VRF burden showed a small association with depressive symptoms at follow-up. However, there was no evidence that fractional anisotropy (FA) of white matter tracts mediated this association. Additional analyses also yielded no mediating effects using alternative operationalisations of VRF burden, mean diffusivity (MD) of single tracts, or overall average of tract-based white matter microstructure (global FA, global MD, white matter hyperintensity volume).

Our results lend no support to the hypothesis that disconnection of white matter tracts underlies the association between VRF burden and depressive symptoms, while highlighting the relevance of using longitudinal data to directly test pathways linking vascular and mental health.