Unlocking the Potential of Repetitive Transcranial Magnetic Stimulation in Alzheimer's Disease: A Meta-Analysis of Randomized Clinical Trials to Optimize Intervention Strategies

Background: Repetitive transcranial magnetic stimulation (rTMS) is an advanced and noninvasive technology that uses pulse stimulation to treat cognitive impairment. However, its specific effects have always been mixed with those of cognitive training, and the optimal parameter for Alzheimer's disease (AD) intervention is still ambiguous. Objective: This study aimed to summarize the therapeutic effects of pure rTMS on AD, excluding the influence of cognitive training, and to develop a preliminary rTMS treatment plan. Methods: Between 1 January 2010 and 28 February 2023, we screened randomized controlled clinical trials from five databases (PubMed, Web of Science, Embase, Cochrane, and ClinicalTrials. gov). We conducted a meta-analysis and systematic review of treatment outcomes and rTMS treatment parameters. Result: A total of 4,606 articles were retrieved. After applying the inclusion and exclusion criteria, 16 articles, comprising 655 participants (308 males and 337 females), were included in the final analysis. The findings revealed that rTMS significantly enhances both global cognitive ability (p = 0.0002, SMD= 0.43, 95% CI = 0.20-0.66) and memory (p = 0.009, SMD= 0.37, 95% CI = 0.09-0.65). Based on follow-up periods of at least 6 weeks, the following stimulation protocols have demonstrated efficacy for AD: stimulation sites (single or multiple targets), frequency (20 Hz), stimulation time (1-2 s), interval (20-30 s), single pulses (<= 2500), total pulses (>20000), duration (>= 3 weeks), and sessions (>= 20). Conclusions: This study suggests that rTMS may be an effective treatment option for patients with AD, and its potential therapeutic capabilities should be further developed in the future.