Background: Cross-sectional studies have shown that late-onset depression is associated with larger deep white matter lesions (WMLs) and subcortical gray matter lesions (GMLs). In a longitudinal analysis, we examined changes in deep WMLs and subcortical GMLs in older depressed and nondepressed subjects over a 4-year period.

Methods: Brain magnetic resonance imaging (MRI) scans were obtained on 164 depressed and 126 healthy subjects aged 60 years or older at baseline, and 2 and 4 years after recruitment. WMLs and GMLs were measured using a semiautomated technique. We used repeated-measures analysis of covariance to determine cross-sectional lesion volume differences, whether lesion volume changes differed between patients and controls, and the effect of lesion volume changes on outcome in late-life depression.

Results: Mean volumes of lesions for the depressive group were 6.51, 8.18 and 7.75 cm2 for WMLs and 0.23, 0.30 and 0.34 cm2 for GMLs at baseline, 2-year and 4-year follow-up, respectively. Mean volumes of lesions for the control group were 4.83, 6.22 and 6.45 cm2 for WMLs and 0.17, 0.25 and 0.23 cm2 for GMLs at baseline, 2-year and 4-year follow-up, respectively. Cross-sectional between-group mean lesion volumes were significantly different for each measure. However, the pattern of WML and GML volume changes over time was not significantly different between groups. Treatment outcome was associated with changes in total and white matter lesion volume over time.

Conclusions: Lesion volume progression is associated with aging and the pathological condition of late-life depression. The mechanisms that produce these progressive lesion changes remain unclear. Treatments aimed at arresting lesion progression may play a role in the management of late-life depression.