Effects and safety of repetitive transcranial magnetic stimulation on cognitive outcomes in mild cognitive impairment: a systematic review and meta-analysis

Background Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique that has been increasingly investigated as a potential treatment for mild cognitive impairment (MCI). However, its clinical efficacy remains uncertain due to heterogeneous findings across studies. Methods A systematic review and meta-analysis of randomized controlled trials comparing active rTMS with sham stimulation or matched control interventions was conducted. Electronic databases were searched from inception. Eligible studies included patients with MCI and reported cognitive outcomes using validated scales, including the Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), or Rivermead Behavioral Memory Test (RBMT). Results Fourteen studies contributing 15 datasets were included. Compared with sham or control interventions, rTMS was associated with higher post-intervention scores on the MoCA, MMSE, and RBMT. For the primary MoCA outcome, the pooled effect estimate was significant but accompanied by substantial between-study heterogeneity (Hedges’ g = 1.46, 95% CI 0.97 to 1.94; p < 0.001; I 2 = 86.0%). Exploratory subgroup analyses showed significant between-subgroup differences according to stimulation frequency ( p = 0.021) and stimulation site ( p < 0.001), whereas the difference according to risk of bias was not statistically significant ( p = 0.114). Among the 10 datasets reporting quantitative safety outcomes, no significant increase in adverse events was observed compared with sham stimulation (RR = 1.25, 95% CI 0.76 to 2.04; p = 0.374). Conclusion rTMS may improve cognitive test performance in patients with MCI. However, substantial between-study heterogeneity limits the precision and generalizability of the estimated treatment effect. Although exploratory subgroup analyses suggested variation according to stimulation frequency and site, these findings do not establish definitive effect modifiers or optimal stimulation parameters. Further well-designed, adequately powered trials with rigorous blinding, standardized protocols, and clinically meaningful outcomes are needed to clarify the magnitude and clinical relevance of rTMS effects in MCI.