Pearcy, Leigh B.; Costa, Ana Paula; Butters, Meryl A.; Krafty, Robert; Boyd, Brian D.; Banihashemi, Layla; Szymkowicz, Sarah M.; Landman, Bennett A.; Ajilore, Olusola; Taylor, Warren D.; Andreescu, Carmen; Karim, Helmet T. (2026).听.听American Journal of Geriatric Psychiatry, 34(6), 844鈥�856.听
This study looks at how changes in brain structure are linked to the return of depression in older adults. Specifically, it focuses on聽white matter hyperintensities (WMH)听补苍诲听hypointensities (WMh)鈥攁reas in brain scans that appear unusually bright or dark and are thought to reflect small blood vessel damage and increased vascular (blood flow鈥搑elated) risk. These markers are commonly seen in older individuals and have been associated with late-life depression (LLD), but it has been unclear whether changes in these brain features over time contribute to depression coming back after recovery.
To investigate this, researchers followed 223 older adults (average age about 67), including people whose depression had improved (remitted LLD) and a comparison group without depression. Brain scans were taken every 8 months over two years to track changes in WMh. During this period, about half of the participants who had recovered from depression experienced a relapse. The researchers found that people who relapsed already had higher levels of WMh at the start of the study compared to those without depression. However, the聽rate at which these brain changes increased over time was not significantly different between groups. When looking more closely, individuals who started with high WMh levels and also showed faster accumulation over time had nearly three times the risk of relapse compared to those with low levels and slow changes.
Overall, the findings suggest that having a higher burden of these brain changes at baseline is an important risk factor for depression returning in older adults, while the speed of progression alone may be less informative. However, people with both high initial levels and rapid increases may be at especially high risk and could benefit from closer monitoring and care to help prevent relapse.
Figure. 1聽Mixed effects model predictions. (A), (B): Results of the model comparing HC vs. remLLD. (C), (D): Results comparing HC vs. REM vs. EarlyREL vs. LateREL. EarlyREL and LateREL represent individuals that relapse within 250 days of baseline and after 250 days of baseline, respectively. Both models adjusted for time (days since baseline), vascular disease burden using CIRS-G, age at baseline, ICV at baseline, sex, education, race, study site, group, and time * group effects.