{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:30:39Z","timestamp":1790188239621,"version":"4.1.0"},"reference-count":88,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T00:00:00Z","timestamp":1745280000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Repetitive transcranial magnetic stimulation (rTMS) is emerging as a promising non-invasive intervention for Alzheimer\u2019s disease (AD), yet therapeutic outcomes remain inconsistent across studies. This meta-analysis aimed to evaluate the cognitive benefits of rTMS in AD patients, with a specific focus on stimulation targets and protocols variations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A systematic literature search was conducted in PubMed, Web of Science, Embase, and Cochrane Library for relevant English-language studies published up to 31 May 2024. Cognitive outcomes were assessed using the Mini-Mental State Examination (MMSE) and Alzheimer\u2019s Disease Assessment Scale-Cognitive Section (ADAS-Cog). Data were pooled using a random-effects model, with standardized mean difference (SMD) or mean differences (MD) and 95% confidence intervals (CI) calculated. Subgroup analyses were performed to examine the effects of stimulation targets, protocol variations and population demographics on rTMS efficacy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twenty-two studies involving 874 participants were included in this meta-analysis. Overall, rTMS significantly improved cognitive function (SMD = 0.27; 95% CI = 0.14\u20130.41; <jats:italic>p<\/jats:italic> &amp;lt; 0.0001), showing that the efficacy of rTMS varied by stimulation target and protocol. Stimulation of the dorsolateral prefrontal cortex (DLPFC) led to significant cognitive improvement (SMD = 0.49, 95% CI = \u22120.26 to 0.73; <jats:italic>p<\/jats:italic> &amp;lt; 0.0001), whereas bilateral DLPFC stimulation showed no significant improvement (SMD = 0.13; 95% CI = \u22120.40 to 0.66; <jats:italic>p<\/jats:italic> = 0.62). Stimulating the parietal lobe or associated regions produced moderate cognitive benefits (SMD = 0.29; 95% CI = 0.03\u20130.55; <jats:italic>p<\/jats:italic> = 0.03). Notably, multi-target stimulation over the bilateral DLPFC, parietal lobes, Wernicke\u2019s area, and Broca\u2019s area also showed substantial cognitive improvement (MD = 2.85; 95% CI = 1.69\u20134.00; <jats:italic>p<\/jats:italic> &amp;lt; 0.00001). Additionally, subgroup analysis based on geographical background revealed greater effects in studies conducted in Asia (SMD = 0.40, 95% CI = 0.14\u20130.65; <jats:italic>p<\/jats:italic> &amp;lt; 0.003).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>rTMS is an effective intervention for cognitive enhancement in AD, with its efficacy significantly influenced by stimulation target and protocol. Notably, the greater cognitive benefits observed in Asian populations suggest a potential role of genetic and demographic factors that warrant further investigation. These findings contribute to the development of optimized, personalized rTMS protocols for AD treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Systematic review registration<\/jats:title><jats:p><jats:uri>https:\/\/www.crd.york.ac.uk\/PROSPERO\/recorddashboard<\/jats:uri>, CRD42023434084.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnagi.2025.1536573","type":"journal-article","created":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T05:27:30Z","timestamp":1745299650000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Comparative efficacy of rTMS on different targets in Alzheimer\u2019s disease: a systematic review and meta-analysis"],"prefix":"10.3389","volume":"17","author":[{"given":"Yushu","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajia","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qifan","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxia","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongxu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1564","DOI":"10.1016\/j.neurobiolaging.2011.06.007","article-title":"Resting state fMRI in Alzheimer\u2019s disease: Beyond the default mode network.","volume":"33","author":"Agosta","year":"2012","journal-title":"Neurobiol. 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