Background: Arterial stiffness may contribute to depression via cerebral microvascular damage, but evidence for this is scarce. We therefore investigated the association between arterial stiffness and depressive symptoms and the potential mediating role of cerebral small vessel disease therein.

Methods: This cross-sectional study included 2,058 participants (mean age 79.6 years; 59.0% women) of the AGES-Reykjavik study. Arterial stiffness (carotid-femoral pulse wave velocity, CFPWV), depressive symptoms (15-item geriatric depression scale, GDS-15) and cerebral small vessel disease (magnetic resonance imaging) were determined. Manifestations of cerebral small vessel disease included higher white matter hyperintensity volume, subcortical infarcts, cerebral microbleeds, Virchow-Robin spaces and lower total brain parenchyma volume.

Results: Higher CFPWV was associated with a higher GDS-15 score, after adjustment for age, sex, education level, smoking, digit symbol substitution test score, gait speed, mean arterial pressure, heart rate and cardiovascular risk factors. Additional adjustment for white matter hyperintensity volume or subcortical infarcts attenuated the association between CFPWV and the GDS-15 score, which became statistically not significant. Formal mediation tests showed that the mediating effects of white matter hyperintensity volume and subcortical infarcts were statistically significant. Virchow-Robin spaces, cerebral microbleeds and cerebral atrophy did not mediate the association between CFPWV and depressive symptoms.

Conclusions: Higher arterial stiffness is associated with more depressive symptoms; this association is partly mediated by white matter hyperintensity volume and subcortical infarcts. This study supports the hypothesis that arterial stiffness leads to depression in part via cerebral small vessel disease.