The role of repetitive transcranial magnetic stimulation (rTMS) in the treatment of cognitive impairment in patients with Alzheimer's disease: A systematic review and meta-analysis

J Neurol Sci. 2019 Mar 15:398:184-191. doi: 10.1016/j.jns.2019.01.038. Epub 2019 Jan 24.


Background: Although repetitive transcranial magnetic stimulation (rTMS) has been considered a potentially effective treatment for cognitive impairment in patients with Alzheimer's disease (AD), previous studies have produced inconsistent results. The objective of this meta-analysis was to evaluate the effects of rTMS on cognitive function in patients with AD.

Methods: PubMed, EMBASE, Web of Science, MEDLINE and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for relevant terms. Abstracts of all papers were carefully reviewed, followed by data extraction, quality assessment, data synthesis and subgroup analyses.

Result: A total of 12 studies with 231 patients were included, with 8 randomized controlled studies and 4 self-controlled studies. Eleven studies used high frequency rTMS (≥ 5 Hz), but only one study directly compared the difference between low-frequency (1 Hz) and high-frequency (20 Hz). Random-effects analysis revealed that rTMS could significantly improve cognition compared with sham-rTMS (SMD: 0.60, 95% CI: 0.35-0.85, P < .0001). In subgroup analyses, the effect for stimulation at a single target was 0.13 (95% CI: -0.35-0.62) and multiple targets 0.86 (95% CI: 0.18-1.54). Treatment for ≤3 sessions produced an effect of 0.29 (95% CI: -1.04-1.62), whereas treatment for ≥5 sessions produced an effect of 2.77 (95% CI: 2.22-3.32). No differences were found for rTMS combined with medication or cognitive training.

Conclusions: rTMS can significantly improve cognitive ability in patients with mild to moderate AD. Stimulation of multiple sites and long-term treatment are better at improving AD-associated cognitive performance. Furthermore, some novel interventional targets, like precuneus (PC), may be a more effective therapeutic site to improve memory in AD.

Keywords: Alzheimer's disease; Cognitive impairment; MMSE; Meta-analysis; Systematic review; Transcranial magnetic stimulation.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / psychology*
  • Alzheimer Disease / therapy*
  • Clinical Trials as Topic / methods
  • Cognitive Dysfunction / diagnosis
  • Cognitive Dysfunction / psychology*
  • Cognitive Dysfunction / therapy*
  • Humans
  • Transcranial Direct Current Stimulation / methods*
  • Transcranial Direct Current Stimulation / trends
  • Transcranial Magnetic Stimulation / methods*
  • Transcranial Magnetic Stimulation / trends
  • Treatment Outcome