Repetitive Transcranial Magnetic Stimulation in Alzheimer's Disease Cognitive Impairment: A Narrative Review of Clinical Trials.

BACKGROUND AND AIMS: Alzheimer's disease (AD), primarily characterized by cognitive impairment, places an immense burden on patients and caregivers. Non-invasive neuromodulation with repetitive transcranial magnetic stimulation has been proposed to improve cognition in mild to moderate AD. This narrative review aimed to summarize clinical trial evidence on the effects, safety, and tolerability of rTMS for AD-related cognitive impairment and to identify research gaps.

METHODS

A narrative review of clinical trials was performed. PubMed/MEDLINE, Embase, Cochrane Google scholar, and Scopus were searched from inception to January 25, 2025, using terms for "repetitive transcranial magnetic stimulation", "Alzheimer's disease", "cognitive impairment", "clinical trials", and "randomized controlled trial". Clinical trials of active rTMS versus sham or treatment-as-usual in adults with mild to moderate AD that reported validated cognitive outcomes were included. Data on rTMS protocols, cognitive measures, adverse effects, and follow-up were extracted and synthesized narratively without statistical pooling.

RESULTS

14 trials were included. Across most studies, rTMS delivered at 5-20 Hz for 4 to 12 weeks, at least 5 days per week, was associated with improved cognitive function. Improvements were reported on tools such as the MMSE, CDR-SB, SIB, and ADAS-Cog, with statistically significant differences versus sham in most trials [p < 0.05], and some evidence of sustained benefit at follow-up. rTMS was generally safe and tolerable. Reported adverse effects were mild to moderate and included transient headache, scalp or skin discomfort, pain, and fatigue. Preliminary evidence also suggested potential neuropsychiatric benefits. However, substantial heterogeneity in duration, frequency, treatment plan, targets, and outcome measures limited definitive conclusions.

CONCLUSION

rTMS appears safe in the short term and may be linked to short-term cognitive and neuropsychiatric gains in mild to moderate AD. However, marked protocol heterogeneity, small sample sizes, short follow-up, and risk of bias limit certainty and prevent identification of optimal parameters. rTMS is not ready for routine AD care. Larger, sham-controlled trials with standardized protocols and biomarker or long-term outcomes are needed.