TDCS Modulates Inflammatory Markers to Improve Post-Stroke Cognitive Impairment and Depression: An Exploratory Randomized Trial

Background Peripheral inflammatory markers may serve as indicators of cognitive impairment and depression after ischemic stroke. Post-stroke cognitive impairment hinders rehabilitation and quality of life. Transcranial direct current stimulation (tDCS) is a promising non-invasive intervention, but its link to inflammatory changes and clinical improvement remains unclear. Objective To evaluate tDCS effects on cognition and depression in stroke patients, and to examine if inflammatory marker changes underlie these effects. Methods Sixty patients were randomized to an experimental group (EG, n = 30) receiving active tDCS (2 mA, 20 minutes/day over affected dorsolateral prefrontal cortex) or a control group (CG, n = 30) receiving sham stimulation, alongside standard rehabilitation for 4 weeks. Serum interleukin-1β ( IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) levels were measured by enzyme-linked immunosorbent assay (ELISA) pre- and post-intervention. Cognition and depression were assessed using Montreal Cognitive Assessment (MoCA) and Hamilton Depression Scale (HAMD). Results Post-intervention, only the EG showed significant reductions in IL-6 and TNF-α (both P < .01), with no change in IL-1β or IL-10 ( P > .05). The EG demonstrated greater improvement in MoCA and HAMD scores than the CG ( P = .01 and .04). Changes in IL-6 (ΔIL-6) and TNF-α (ΔTNF-α) predicted improvements in MoCA scores (ΔMoCA, R 2 = .607, P < .01). ΔIL-6 and disease duration predicted improvements in HAMD scores (ΔHAMD, R 2 = .501, P < .01). Conclusion tDCS combined with conventional rehabilitation therapies may reduce pro-inflammatory cytokine levels and improve cognitive and depressive symptoms, supporting its potential application as an anti-inflammatory neurorehabilitation therapy. Clinical Trial registration Study on the mechanism of transcranial direct current stimulation in the intervention of working memory decline after stroke, https://www.chictr.org.cn/showproj.html?proj=208836 , ChiCTR2300077242