Repetitive transcranial magnetic stimulation for the treatment of Alzheimer's disease: A systematic review and meta-analysis of randomized controlled trials

PLoS One. 2018 Oct 12;13(10):e0205704. doi: 10.1371/journal.pone.0205704. eCollection 2018.


Background: Several studies have demonstrated that repetitive transcranial magnetic stimulation (rTMS) may have a beneficial effect in Alzheimer's disease (AD). Nevertheless, the clinical benefit of rTMS for AD remains inconclusive.

Objective: This systematic review and meta-analysis aimed to evaluate the efficacy and safety of rTMS in AD.

Methods: We searched PubMed, Embase and Cochrane for randomized controlled trials (RCTs) of rTMS for AD. We calculated pooled estimates of mean difference (MD) with 95% confidence intervals (CI). The protocol was registered at International Prospective Register of Systematic Reviews (PROSPERO) (number CRD42018089990).

Results: Five RCTs involving 148 participants were included in this review. Compared with sham stimulation, high-frequency rTMS led to a significant improvement in cognition as measured by ADAS-cog (MD = -3.65, 95% CI -5.82 to -1.48, p = 0.001), but not MMSE (MD = 0.49, 95% CI -1.45 to 2.42, p = 0.62). High-frequency rTMS also improved the global impression in comparison to the placebo (MD = -0.79, 95% CI -1.24 to -0.34, p = 0.0006). There was no significant difference in mood (MD = -1.36, 95% CI -3.93 to 1.21, p = 0.30) and functional performance (MD = 0.59, 95% CI -1.21 to 2.38, p = 0.52) between high-frequency rTMS and sham groups. Only one trial included low-frequency rTMS reported no significant improvement in cognition, mood and functional performance. Few mild adverse events were observed in both the rTMS and sham groups.

Conclusions: RTMS is relatively well tolerated, with some promise for cognitive improvement and global impression in patients with AD. Our findings also indicate the variability between ADAS-cog and MMSE in evaluating global cognitive impairment.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Alzheimer Disease / therapy*
  • Humans
  • Randomized Controlled Trials as Topic
  • Transcranial Direct Current Stimulation* / methods

Grants and funding

This work was supported by the National Natural Science Foundation of China (No. 81600970) and Nanjing Medical Science and Technology Development Project (YKK17257). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.