Efficacy and Durability of Repetitive Transcranial Magnetic Stimulation on Cognitive Function in Patients With Mild-to-Moderate Alzheimer's Disease: A Systematic Review and Meta-Analysis.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that has shown potential for improving cognitive function in Alzheimer's disease (AD), though findings remain inconsistent. This meta-analysis evaluated the efficacy and durability of rTMS in patients with mild to moderate AD and explored potential moderating factors. Randomised controlled trials (RCTs) comparing active rTMS with sham stimulation were identified through systematic searches of major databases. Effect sizes were calculated using Hedges' g, with random-effects models applied. Risk of bias was assessed using the Cochrane RoB 2 tool. Five RCTs (N = 143) were included in the primary analysis. rTMS showed a small-to-moderate improvement in MMSE scores (g = 0.41, 95% CI [0.06, 0.75], p = 0.021, I2 = 6.5%). Excluding two studies with methodological concerns yielded a similar effect (g = 0.46), though with wider confidence intervals. Sensitivity analysis including studies with change scores confirmed the robustness of results (g = 0.48). Given the limited number of studies (k < 10), formal publication bias tests and trim-and-fill adjustment were not applied, in line with current methodological guidance. Notably, all five studies employed excitatory stimulation protocols (high-frequency rTMS or iTBS), with four of five targeting the left dorsolateral prefrontal cortex (DLPFC), suggesting that excitatory stimulation of key cognitive network hubs represents the most consistent evidence base to date. Meta-regression identified treatment duration as a significant moderator (β = -0.193, p = 0.034), suggesting shorter, more intensive protocols may be more effective. Follow-up analyses indicated a nonsignificant trend towards sustained benefits (g = 0.25), while time-trend analysis demonstrated a stable overall effect (g = 0.38). In conclusion, rTMS provides modest cognitive benefits in mild to moderate AD, with excitatory protocols targeting the left DLPFC showing the most consistent efficacy and treatment duration influencing outcomes. However, evidence remains limited, highlighting the need for larger, standardised, multi-centre trials with long-term follow-up.