High‐Intensity Alternating Current Stimulation as an Add‐On to Multidisciplinary Intensive Rehabilitation for Parkinson's Disease: A Randomized Controlled Trial

ABSTRACT Aims In this randomized, double‐blind, sham‐controlled trial, we explored whether high‐intensity transcranial alternating current stimulation (Hi‐tACS), as an add‐on to multidisciplinary intensive rehabilitation therapy (MIRT), could yield more durable quality of life (QoL) improvements than MIRT alone. Methods Sixty patients with Parkinson's disease (PwP) (Hoehn and Yahr stages 1–3, aged 45–70) were assigned (1:1) to receive 10 days of MIRT with either twice‐daily Hi‐tACS (15 mA, 77.5 Hz, 40 min/session) or sham stimulation. The primary outcome was the longitudinal change in the 39‐item Parkinson's Disease Questionnaire (PDQ‐39) total score from baseline to 4, 12, and 24 weeks after intervention. Secondary outcomes included changes in motor and non‐motor symptom scales. Adverse events were monitored throughout the intervention period. Results Generalized estimating equation analysis revealed a significant group‐by‐time interaction for PDQ‐39 total scores ( P group × time = 0.008). The Hi‐tACS+MIRT group demonstrated significantly greater reductions in PDQ‐39 scores than the sham‐Hi‐tACS+MIRT group at 4 weeks (T2: effect size = 0.68, 95% CI: 0.14–1.21; P FDR = 0.009), 12 weeks (T3: effect size = 1.43, 95% CI: 0.80–2.05; P FDR = 0.003), and 24 weeks (T4: effect size = 1.26, 95% CI: 0.65–1.85; P FDR < 0.001). In addition, the Hi‐tACS+MIRT group exhibited superior improvements in depression and apathy. Adverse events were mild and infrequent, with no serious adverse events reported. Conclusions This trial demonstrated that the Hi‐tACS add‐on to MIRT could maintain long‐term improvements in QoL and improve non‐motor symptoms for PwP, providing a new strategy for PwP rehabilitation.