Repetitive transcranial magnetic stimulation for cognitive impairment in Alzheimer's disease: a meta-analysis of randomized controlled trials

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation technique for Alzheimer’s disease (AD). rTMS, with high- or low-frequency, is thought to enhance or inhibit the cortical activities, respectively. This meta-analysis of randomized controlled trials (RCTs) was to summarize the efficacy of the rTMS on the cognition of AD patients and to identify its potential influential factors. Literature from the Pubmed, Embase, Cochrane Library and Web of Science were searched and screened to identify eligible studies. Standardized mean difference (SMD) and 95% confidence interval were used to evaluate the therapeutic effects of rTMS. Subgroup analyses were performed to investigate the influential factors. Ten studies with 15 trials involving 240 patients were included. Compared with sham stimulation, rTMS could significantly improve cognition in AD (SMD, 0.42; 95% CI 0.18–0.67; P = 0.0006). Subgroup analysis suggested significant cognitive enhancement in participants receiving rTMS on multiple sites rather than on single site, and in patients receiving rTMS of more than 10 sessions, but not ≤ 10 sessions. Compared with rTMS as the single therapeutic method, rTMS with concurrent cognitive training seemed to produce greater improvement. Moreover, 20 Hz rTMS, seemed to be more effective than 10 Hz or 1 Hz rTMS. Furthermore, patients with higher education, or with mild-to-moderate AD were more likely to benefit from rTMS than patients with lower education, or with severe dementia, respectively. Based on the current evidence, rTMS was an effective therapy for cognitive impairment in AD. Large RCTs are warranted to further validate the results of our subgroup analyses.