Cognitive Profiles in Treatment-Resistant Late-Life Depression and Their Impact on Treatment Outcomes

Late-life depression (LLD) is associated with cognitive impairment, but substantial heterogeneity exists among patients. Data on the extent of cognitive impairments are inconclusive, particularly in patients with treatment-resistant depression (TRD). We investigated the cognitive profiles of patients with treatment-resistant versus nonresistant LLD and aimed to identify distinct cognitive subgroups. We also examined whether cognitive subgroups responded differentially to treatment with bilateral repetitive transcranial magnetic stimulation (rTMS).

A total of 165 patients with LLD were divided into treatment-resistant and nonresistant groups and compared with healthy control participants on measures of executive function, information processing speed, verbal learning, and memory. Cluster analysis identified subgroups based on cognitive scores. Demographic and clinical variables, as well as outcomes with bilateral rTMS, were compared between cognitive subgroups.

Patients with LLD, particularly TRD, exhibited significantly worse cognitive performance than healthy controls. A 3-cluster solution was found, including cognitively intact (n = 89), cognitively diminished (n = 29), and impaired memory (n = 47) subgroups. Both the cognitively diminished and impaired memory subgroups had more anxiety symptoms and a higher proportion of patients with TRD than the cognitively intact group, although the latter difference did not survive multiple comparison correction. No significant differences were observed in outcomes to rTMS treatment.

Patients with LLD exhibited impairments across cognitive domains, which were more pronounced in TRD. Three cognitive subgroups responded similarly to rTMS treatment, indicating its effectiveness across cognitive profiles, especially when medications are not tolerated. Future research should examine the relationships among cognitive subgroups, cognitive decline, and neurodegeneration.