Effects of rTMS treatment on global cognitive function in Alzheimer's disease: A systematic review and meta-analysis

BACKGROUND: Although repetitive transcranial magnetic stimulation (rTMS) has been extensively studied in patients with Alzheimer's disease (AD), the clinical evidence remains inconsistent. The purpose of this meta-analysis was to evaluate the effects of rTMS on global cognitive function in patients with AD. METHODS: An integrated literature search using 4 databases (PubMed, Web of Science, Embase, and Cochrane Library) was performed to identify English language articles published up to October 6, 2021. We pooled Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) scores using a random-effects model via RevMan 5.4 software. We calculated estimates of mean differences (MD) with 95% confidence intervals (CI). The primary outcomes were pre-post treatment changes in global cognition as measured using MMSE and ADAS-Cog immediately after rTMS treatment, and the secondary outcome was duration of cognitive improvement (1–1.5 and ≥3 months). RESULTS: Nine studies with 361 patients were included in this meta-analysis. The results showed that rTMS significantly improved global cognitive function immediately following rTMS treatment [(MD) 1.82, 95% confidence interval (CI) 1.41–2.22, p < 0.00001, MMSE; 2.72, 95% CI, 1.77–3.67, p < 0.00001, ADAS-Cog], and the therapeutic effects persisted for an extended duration (2.20, 95% CI, 0.93–3.47, p =0.0007, MMSE; 1.96, 95% CI, 0.96–2.95, p = 0.0001, ADAS-Cog). Subgroup analyses showed that high frequency rTMS targeted to the left dorsolateral prefrontal cortex (DLPFC) for over 20 sessions induced the greatest cognitive improvement, with effects lasting for more than 1 month after the final treatment. There were no significant differences in dropout rate (p > 0.05) or adverse effect rate (p > 0.05) between the rTMS and control groups. CONCLUSIONS: Repetitive TMS is a potentially effective treatment for cognitive impairment in AD that is safe and can induce long-lasting effects. Our results also showed that ADAS-cog and MMSE differed in determination of global cognitive impairment. SYSTEMATIC REVIEW REGISTRATION: http://www.crd.york.ac.uk/PROSPERO, PROSPERO CRD42022315545.