Active rTMS not superior to Sham for Treating Cognitive Impairment in Patients with Alzheimer’s Disease

Abstract

Abstract Background- We report results of a large multisite double-blind randomized trial investigating the short and long-term efficacy of repetitive transcranial magnetic stimulation (rTMS) applied to patients with Alzheimer’s disease (AD) at mild to moderate stages, in doses of either 2 or 4 weeks of treatment (5 days/week), whilst compared with 4 weeks of sham TMS. Randomization to treatment group was stratified based on age and severity. The objectives of this study were to: 1) investigate the efficacy of active rTMS versus sham, 2) investigate the effect of dose of treatment (2 or 4 weeks), and 3) investigate the length of benefits from treatment. Methods - The rTMS pulses (20 Hz, 30 pulses/train, 25 trains, 10-s intertrain interval) were applied to the bilateral dorsolateral prefrontal cortex bilaterally using neuro-navigation. We compared the primary outcome measure’s (ADAS-Cog) score changes from pre- to post-treatment, with assessments at baseline and 4 more times up to 6 months post-treatment. Results- Data of 135 patients were analyzed. The mean total ADAS-Cog score at baseline did not differ between the active and sham treatment groups, nor across the three study sites. The overall results show significant cognitive improvement after treatment with either sham or active coils. Conclusion- The results do not support the benefit of active rTMS versus sham for cognitive treatment of mild/moderate AD. We discuss this finding in the context of the existing literature on rTMS therapy for AD, as well as evidence of the sham coil’s potential to induce a low-level current in the brain.