White matter hyperintensities and relapse risk in late-life depression

White matter hyperintensities (WMHs) are associated with late-life depression (LLD) and are considered a hallmark of MRI-defined vascular depression. However, their impact on depression recurrence in LLD is less well known.

We investigated this relationship using data from a 2-year multi-site, longitudinal study, where baseline WMH volumes were obtained using 3 T FLAIR magnetic resonance imaging (MRI) from 145 participants, of which 102 had remitted LLD and 43 were control participants. We analyzed the effect of baseline WMH volume on LLD relapse over 2 years using regression and adjusting for total intracranial volume, age, sex, race, education, and study site. We performed survival analyses using a Cox proportional hazard model to determine whether baseline WMH volume was associated with time to relapse in LLD.

We found that participants with LLD had greater WMH volume at baseline than control participants, but not if accounting for peripheral cardiovascular disease. Participants with LLD who relapsed within 8 months of baseline had larger WMH volume than control participants but did not statistically differ from those that remained remitted; this effect was lost when expanding to participants that relapsed at any point in the 2-year study. WMH burden was not associated with time to relapse, suggesting greater WMH volumes are not indicative of faster relapse rates in LLD.

Our results show that WMH burden may play a role in the early - but not the delayed - relapse of LLD, and they underscore the intricate dynamic of the biological markers underlying LLD treatment response and relapse.