Longitudinal Changes in White Matter Hypointensities in Recurrent Late-Life Depression

White matter hypointensities (WMhs) on T1 and white matter hyperintensities (WMH) on T2-FLAIR are highly correlated and indicate elevated vascular risk in late-life depression (LLD). While larger baseline WMH are associated with depression recurrence, the literature is sparse regarding the longitudinal accumulation of WMh and its association with relapse in older adults.

We investigated the relationship between WMh and LLD recurrence over a 2-year multi-site study. T1 images were collected every 8 months from N = 223 participants, 157 with remitted LLD and 66 comparison participants (mean age 67.5 ± 4.92 years; 67.3% female). A total of 52% of participants in remission experienced relapse. WMh accumulation rates were analyzed across groups defined on relapse status using mixed effects modeling. We extracted individual measures of WMh and divided participants into four groups: baseline WMh load (low, high) x WMh accumulation (slow, rapid) to estimate differences in relapse risk using a Cox model.

The relapse groups were associated with greater baseline WMh than the non-depressed comparison group. WMh accumulation did not differ between non-depressed and remitted LLD participants (β = 0.009, 95% CI: -0.04 to 0.06). Compared to individuals with low baseline WMh and slow accumulation, individuals with high baseline WMh and rapid accumulation had a higher risk of relapse (HR = 2.92, 95% CI: 1.31-6.47).

Greater baseline WMh was associated with relapse after remission in LLD, but the rate of WMh progression was not. Patients with high baseline and rapidly accumulating WMh may warrant closer clinical monitoring due to increased risk of depression relapse.