Brain-cognition relationships and treatment outcome in treatment-resistant late-life depression

Abstract

Older adults with treatment-resistant depression are at significant risk for cognitive impairment. However, the relationship between treatment response and cognitive function in this population is not well-established. We examined neural correlates of executive and memory function, and their relationship with remission to pharmacological treatment in a biomarker study embedded within a clinical trial for late-life treatment-resistant depression. Among participants who completed neuroimaging, better cognition was associated with lower connectivity between components of the default mode and the frontoparietal networks and within the frontoparietal network. Using diffusion imaging data, lower tract integrity in a distributed set of tracts was associated with poorer processing speed. Additionally, gray matter structure was positively associated with cognition. Greater education was also associated with better cognition. Ongoing treatment resistance was predicted by poorer cognition and gray matter structure in cross-validated regularized logistic models. These results identify distinct cross-sectional associations between neural circuits and cognitive function in treatment-resistant late-life depression, and build a predictive model for antidepressant medication response. Late-life depression is hard to treat and presents a risk for dementia. Here, the authors identify neural correlates of cognitive function in late-life depression, and pinpoint clinical symptoms, gray matter loss and worse cognition as robust baseline markers of non-remission to antidepressants.