Effect of combined transcranial direct current stimulation and cognitive training on brain microstructure and network homogeneity in late-life depression: a pilot study

Background: Depression and cognitive decline frequently coexist in older individuals. However, effective treatment options remain limited. Neuromodulation has shown potential beyond traditional cognitive training; however, its specific effects on brain connectivity and white matter structures remain unclear. The purpose of this study was to evaluate the effects of combining transcranial direct current stimulation (tDCS) with cognitive training on white matter microstructure integrity and default mode network (DMN) homogeneity in older adults with cognitive deficits and depressive symptoms. Methods: This double-blind, randomized sham-controlled study compared cognitive training combined with either anodal or sham tDCS in older adults with late-life depression and cognitive decline. Multimodal magnetic resonance imaging was used to assess DMN homogeneity and white matter microstructure at baseline and after 5 weeks of treatment. Results: Cognitive training, whether combined with active or sham tDCS, led to significantly increased fractional anisotropy averaged across all brain regions, indicating an overall improvement in white matter integrity. However, tDCS did not provide additional benefit to white matter integrity. A higher baseline anterior-posterior DMN association correlated with better cognitive function, and treatment remission increased posterior DMN homogeneity. Enhancements in cingulum white matter integrity were associated with improvements in depressive symptoms, cognition, and brain-derived neurotrophic factor levels. Conclusions: Cognitive training leads to improved white matter integrity in older adults experiencing cognitive deficit and depression. Changes in the structural integrity of the cingulum can predict clinical outcomes. No additional benefits of tDCS on white matter integrity or network homogeneity were observed. Clinical trial registration: Registry: Clinical Research Information Service; URL: https://cris.nih.go.kr; Unique identifier: KCT0006594.