Comparative efficacy, tolerability, and acceptability of aducanumab, lecanemab, and donanemab with repetitive transcranial magnetic stimulation on cognitive function in mild cognitive impairment and Alzheimer’s disease: A systematic review and network meta-analysis

BACKGROUND: The U.S. Food and Drug Administration approved three disease-modifying treatments for mild cognitive impairment and early Alzheimer's disease: aducanumab, lecanemab, and donanemab, which showed little efficacy, serious side effects, and are costly. Repetitive transcranial magnetic stimulation (rTMS) may overcome these difficulties by its safe, cheap, and potentially disease-modifying properties that extend beyond Aβ removal. AIMS: We aim to compare the efficacy on cognitive function, tolerability, and acceptability of rTMS with aducanumab, lecanemab, and donanemab in people with mild cognitive impairment and Alzheimer's disease. METHODS: We systematically reviewed relevant randomized placebo-controlled trials in PubMed, the CENTRAL, the CINHAL, and the ClinicalTrials.gov and performed a random-effect network meta-analysis. RESULTS: Nineteen randomized placebo-controlled trials with 6918 participants were included. rTMS was significantly more effective than placebo/sham stimulation. In addition, rTMS was significantly more effective than aducanumab, lecanemab, and donanemab. Furthermore, rTMS was not significantly inferior to placebo/sham stimulation in tolerability and acceptability, whereas aducanumab, lecanemab, and donanemab were significantly inferior to placebo/sham stimulation in tolerability and acceptability. rTMS was significantly superior to lecanemab and donanemab in acceptability. No significant differences were observed in the remaining comparisons. CONCLUSIONS: rTMS may be more effective, tolerable, and acceptable than aducanumab, lecanemab, and donanemab. Long-term direct comparison studies are needed.