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Abstract

Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive neuromodulatory technique that is increasingly being investigated for its therapeutic potential in cognitive impairment associated with dementia and Alzheimer’s disease. This narrative review synthesizes and critically appraises the current evidence surrounding rTMS, with particular focus on clinical efficacy, neurobiological mechanisms, and emerging innovations. High-frequency stimulation over the Dorsolateral Prefrontal Cortex (DLPFC) has consistently demonstrated improvements in memory, executive function, and attention, likely mediated by enhanced synaptic plasticity, increased neurotrophic factor expression, and modulation of large-scale brain networks, such as the default mode and fronto-parietal networks. Recent high-quality studies have built upon earlier research to highlight the comparative efficacy of target-specific stimulation, including precuneus- and parietal-based protocols, as well as multi-site strategies that engage language and associative regions. It also examines the use of TMS-EEG and DMN connectivity as predictors of treatment response, labelporting a shift toward personalized, biomarker-guided rTMS paradigms. Moreover, the synergistic potential of combining rTMS with cognitive training and pharmacotherapy is explored as a promising avenue for multimodal treatment. While preliminary results are encouraging, heterogeneity in study design and stimulation parameters continues to limit the generalizability of the findings. Standardization of protocols, long-term efficacy validation, and large-scale clinical trials remain critical to translating rTMS into routine dementia care.

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2025-10-30
2025-12-16

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References

  1. Francis N. Hanna P. Informal carer experiences of UK dementia services-A systematic review. J. Psychiatr. Ment. Health Nurs. 2022 29 1 116 129 10.1111/jpm.12698 33047451
    [Google Scholar]
  2. Noohi S. Amirsalari S. History, studies and specific uses of repetitive transcranial magnetic stimulation (rTMS) in treating epilepsy. Iran. J. Child. Neurol. 2016 10 1 1 8 27057180
    [Google Scholar]
  3. Brain stimulation therapies Bethesda (MD): National institute of mental health 2024 National Institute of Mental Health (US) Available from:https://www.nimh.nih.gov/health/topics/brain-stimulation-therapies/brain-stimulation-therapies
    [Google Scholar]
  4. Siebner H.R. Funke K. Aberra A.S. Transcranial magnetic stimulation of the brain: What is stimulated? – A consensus and critical position paper. Clin. Neurophysiol. 2022 140 59 97 10.1016/j.clinph.2022.04.022 35738037
    [Google Scholar]
  5. Lefaucheur J.P. Aleman A. Baeken C. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): An update (2014–2018). Clin. Neurophysiol. 2020 131 2 474 528 10.1016/j.clinph.2019.11.002 31901449
    [Google Scholar]
  6. Rossi S. Hallett M. Rossini P.M. Pascual-Leone A. Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin. Neurophysiol. 2009 120 12 2008 2039 [Safety of TMS Consensus Group. 10.1016/j.clinph.2009.08.016 19833552
    [Google Scholar]
  7. Liang X. Xue C. Zheng D. Repetitive transcranial magnetic stimulation regulates effective connectivity patterns of brain networks in the spectrum of preclinical Alzheimer’s disease. Front. Aging Neurosci. 2024 16 1343926 10.3389/fnagi.2024.1343926 38410745
    [Google Scholar]
  8. Casula E.P. Tarantino V. Basso D. Low-frequency rTMS inhibitory effects in the primary motor cortex: Insights from TMS-evoked potentials. Neuroimage 2014 98 225 232 10.1016/j.neuroimage.2014.04.065 24793831
    [Google Scholar]
  9. Chen J. Ma N. Hu G. rTMS modulates precuneus-hippocampal subregion circuit in patients with subjective cognitive decline. Aging 2021 13 1 1314 1331 10.18632/aging.202313 33260151
    [Google Scholar]
  10. Kricheldorff J. Göke K. Kiebs M. Evidence of neuroplastic changes after transcranial magnetic, electric, and deep brain stimulation. Brain Sci. 2022 12 7 929 10.3390/brainsci12070929 35884734
    [Google Scholar]
  11. Gao L. Zhang Y. Sterling K. Song W. Brain-derived neurotrophic factor in Alzheimer’s disease and its pharmaceutical potential. Transl. Neurodegener. 2022 11 1 4 10.1186/s40035‑022‑00279‑0 35090576
    [Google Scholar]
  12. Antonioni A. Martorana A. Santarnecchi E. Hampel H. Koch G. The neurobiological foundation of effective repetitive transcranial magnetic brain stimulation in Alzheimer’s disease. Alzheimers Dement. 2025 21 6 e70337 10.1002/alz.70337 40530618
    [Google Scholar]
  13. Cruciani A. Mancuso M. Sveva V. Using TMS-EEG to assess the effects of neuromodulation techniques: A narrative review. Front. Hum. Neurosci. 2023 17 1247104 10.3389/fnhum.2023.1247104 37645690
    [Google Scholar]
  14. Tang S.T. Chen J.S. Chou W.C. Prevalence of severe depressive symptoms increases as death approaches and is associated with disease burden, tangible social support, and high self-perceived burden to others. support. Care Cancer 2016 24 1 83 91 10.1007/s00520‑015‑2747‑0 25933701
    [Google Scholar]
  15. Investing in treatment for depression and anxiety leads to fourfold return Washington (DC): World bank. 2016 World Bank Available from:https://www.worldbank.org/en/news/press-release/2016/04/13/investing-in-treatment-for-depression-anxiety-leads-to-fourfold-return
    [Google Scholar]
  16. Edinoff A.N. Akuly H.A. Hanna T.A. Selective serotonin reuptake inhibitors and adverse effects: A narrative review. Neurol. Int. 2021 13 3 387 401 10.3390/neurolint13030038 34449705
    [Google Scholar]
  17. Berlim M.T. van den Eynde F. Tovar-Perdomo S. Daskalakis Z.J. Response, remission and drop-out rates following high-frequency repetitive transcranial magnetic stimulation (rTMS) for treating major depression: A systematic review and meta-analysis of randomized, double-blind and sham-controlled trials. Psychol. Med. 2014 44 2 225 239 10.1017/S0033291713000512 23507264
    [Google Scholar]
  18. Breda V. Freire R. Repetitive transcranial magnetic stimulation (rTMS) in major depression. Adv. Exp. Med. Biol. 2024 1456 145 159 10.1007/978‑981‑97‑4402‑2_8 39261428
    [Google Scholar]
  19. George M.S. Lisanby S.H. Avery D. Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder: A sham-controlled randomized trial. Arch. Gen. Psychiatry 2010 67 5 507 516 10.1001/archgenpsychiatry.2010.46 20439832
    [Google Scholar]
  20. Carmi L. Tendler A. Bystritsky A. Efficacy and safety of deep transcranial magnetic stimulation for obsessive-compulsive disorder: A prospective multicenter randomized double-blind placebo-controlled trial. Am. J. Psychiatry 2019 176 11 931 938 10.1176/appi.ajp.2019.18101180 31109199
    [Google Scholar]
  21. Zangen A. Moshe H. Martinez D. Repetitive transcranial magnetic stimulation for smoking cessation: A pivotal multicenter double‐blind randomized controlled trial. World Psychiatry 2021 20 3 397 404 10.1002/wps.20905 34505368
    [Google Scholar]
  22. Edinoff A.N. Hegefeld T.L. Petersen M. Transcranial magnetic stimulation for post-traumatic stress disorder. Front. Psychiatry 2022 13 701348 10.3389/fpsyt.2022.701348 35711594
    [Google Scholar]
  23. Diefenbach G.J. Bragdon L.B. Zertuche L. Repetitive transcranial magnetic stimulation for generalised anxiety disorder: A pilot randomised, double-blind, sham-controlled trial. Br. J. Psychiatry 2016 209 3 222 228 10.1192/bjp.bp.115.168203 27198484
    [Google Scholar]
  24. Raina P. Santaguida P. Ismaila A. Effectiveness of cholinesterase inhibitors and memantine for treating dementia: Evidence review for a clinical practice guideline. Ann. Intern. Med. 2008 148 5 379 397 10.7326/0003‑4819‑148‑5‑200803040‑00009 18316756
    [Google Scholar]
  25. Dementia number of people affected to triple in next 30 years. Geneva: World health organization. 2017 World Health Organization Available from: https://www.who.int/news/item/07-12-2017-dementia-number-of-people-affected-to-triple-in-next-30-years
    [Google Scholar]
  26. Dementia. Geneva: World health organization 2024 Available from: https://www.who.int/news-room/fact-sheets/detail/dementia
    [Google Scholar]
  27. Luo G. Zhang J. Song Z. Effectiveness of non-pharmacological therapies on cognitive function in patients with dementia—A network meta-analysis of randomized controlled trials. Front. Aging Neurosci. 2023 15 1131744 10.3389/fnagi.2023.1131744 36967820
    [Google Scholar]
  28. Esposito S. Trojsi F. Cirillo G. Repetitive transcranial magnetic stimulation (rTMS) of dorsolateral prefrontal cortex may influence semantic fluency and functional connectivity in fronto-parietal network in mild cognitive impairment (MCI). Biomedicines 2022 10 5 994 10.3390/biomedicines10050994 35625731
    [Google Scholar]
  29. Weiler M Stieger KC Long JM Rapp PR Transcranial magnetic stimulation in alzheimer’s disease: Are we ready? eNeuro 2020 7 1 ENEURO.0235-19.2019. 10.1523/ENEURO.0235‑19.2019 31848209
    [Google Scholar]
  30. Mikellides G. Michael P. Tantele M. Repetitive transcranial magnetic stimulation: An innovative medical therapy. Psychiatriki 2021 32 1 67 74 10.22365/jpsych.2021.012 33770749
    [Google Scholar]
  31. Chou Y. Ton That V. Sundman M. A systematic review and meta-analysis of rTMS effects on cognitive enhancement in mild cognitive impairment and Alzheimer’s disease. Neurobiol. Aging 2020 86 1 10 10.1016/j.neurobiolaging.2019.08.020 31783330
    [Google Scholar]
  32. Pagali S.R. Kumar R. LeMahieu A.M. Efficacy and safety of transcranial magnetic stimulation on cognition in mild cognitive impairment, Alzheimer’s disease, Alzheimer’s disease-related dementias, and other cognitive disorders: A systematic review and meta-analysis. Int. Psychogeriatr. 2024 36 10 880 928 10.1017/S1041610224000085 38329083
    [Google Scholar]
  33. Zhang Y. Dong K. Yang J. Comparative efficacy of rTMS on different targets in Alzheimer’s disease: A systematic review and meta-analysis. Front. Aging Neurosci. 2025 17 1536573 10.3389/fnagi.2025.1536573 40336945
    [Google Scholar]
  34. Koch G. Casula E.P. Bonnì S. Effects of 52 weeks of precuneus rTMS in Alzheimer’s disease patients: A randomized trial. Alzheimers Res. Ther. 2025 17 1 69 10.1186/s13195‑025‑01709‑7 40176122
    [Google Scholar]
  35. Zhang X. Zhu L. Li Y. Yu H. Wang T. Chu X. Therapeutic potential and mechanisms of repetitive transcranial magnetic stimulation in Alzheimer’s disease: A literature review. Eur. J. Med. Res. 2025 30 1 233 10.1186/s40001‑025‑02493‑8 40186275
    [Google Scholar]
  36. Wei Z. Fu J. Liang H. Liu M. Ye X. Zhong P. The therapeutic efficacy of transcranial magnetic stimulation in managing Alzheimer’s disease: A systemic review and meta-analysis. Front. Aging Neurosci. 2022 14 980998 10.3389/fnagi.2022.980998 36147701
    [Google Scholar]
  37. Chen L. Oei T.P. Zhou R. The cognitive control mechanism of improving emotion regulation: A high-definition tDCS and ERP study. J. Affect. Disord. 2023 332 19 28 10.1016/j.jad.2023.03.059 36958485
    [Google Scholar]
  38. Eldaief M.C. Halko M.A. Buckner R.L. Pascual-Leone A. Transcranial magnetic stimulation modulates the brain’s intrinsic activity in a frequency-dependent manner. Proc. Natl. Acad. Sci. USA 2011 108 52 21229 21234 10.1073/pnas.1113103109 22160708
    [Google Scholar]
  39. Danzer S.C. Crooks K.R.C. Lo D.C. McNamara J.O. Increased expression of brain-derived neurotrophic factor induces formation of basal dendrites and axonal branching in dentate granule cells in hippocampal explant cultures. J. Neurosci. 2002 22 22 9754 9763 10.1523/JNEUROSCI.22‑22‑09754.2002 12427830
    [Google Scholar]
  40. Jiao S.S. Shen L.L. Zhu C. Brain-derived neurotrophic factor protects against tau-related neurodegeneration of Alzheimer’s disease. Transl. Psychiatry 2016 6 10 e907 10.1038/tp.2016.186 27701410 PMC5315549
    [Google Scholar]
  41. Larson J. Munkácsy E. Theta-burst LTP. Brain Res. 2015 1621 38 50 10.1016/j.brainres.2014.10.034 25452022
    [Google Scholar]
  42. Anil S. Lu H. Rotter S. Vlachos A. Repetitive transcranial magnetic stimulation (rTMS) triggers dose-dependent homeostatic rewiring in recurrent neuronal networks. bioRxiv 2023 10.1101/2023.03.20.533396
    [Google Scholar]
  43. Iezzi E. labelpa A. Conte A. Li Voti P. Bologna M. Berardelli A. Short-term and long-term plasticity interaction in human primary motor cortex. Eur. J. Neurosci. 2011 33 10 1908 1915 10.1111/j.1460‑9568.2011.07674.x 21488986
    [Google Scholar]
  44. Loo C.K. McFarquhar T.F. Mitchell P.B. A review of the safety of repetitive transcranial magnetic stimulation as a clinical treatment for depression. Int. J. Neuropsychopharmacol. 2008 11 1 131 147 10.1017/S1461145707007717 17880752
    [Google Scholar]
  45. Mikellides G Michael P Psalta L Schuhmann T Sack AT A retrospective naturalistic study comparing the efficacy of ketamine and repetitive transcranial magnetic stimulation for treatmentresistant depression front psychiatry 2022 12 784830. 10.3389/fpsyt.2021.784830 35095600 PMC5846193
    [Google Scholar]
  46. McClintock SM Reti IM Carpenter LL Consensus recommendations for the clinical application of repetitive transcranial magnetic stimulation (rTMS) in the treatment of depression J Clin Psychiatry 2018 79 1 16cs10905.National Network of Depression Centers rTMS Task Group; American Psychiatric Association Council on Research Task Force on Novel Biomarkers and Treatments. 10.4088/JCP.16cs10905 28541649 PMC5846193
    [Google Scholar]
  47. Liao X. Li G. Wang A. Repetitive transcranial magnetic stimulation as an alternative therapy for cognitive impairment in alzheimer’s disease: A meta-analysis. J. Alzheimers Dis. 2015 48 2 463 472 10.3233/JAD‑150346 26402010
    [Google Scholar]
  48. Hsu W.Y. Ku Y. Zanto T.P. Gazzaley A. Effects of noninvasive brain stimulation on cognitive function in healthy aging and Alzheimer’s disease: A systematic review and meta-analysis. Neurobiol. Aging 2015 36 8 2348 2359 10.1016/j.neurobiolaging.2015.04.016 26022770
    [Google Scholar]
  49. Freitas C. Mondragón-Llorca H. Pascual-Leone A. Noninvasive brain stimulation in Alzheimer’s disease: Systematic review and perspectives for the future. Exp. Gerontol. 2011 46 8 611 627 10.1016/j.exger.2011.04.001 21511025
    [Google Scholar]
  50. Rabey J.M. Dobronevsky E. Aichenbaum S. Gonen O. Marton R.G. Khaigrekht M. Repetitive transcranial magnetic stimulation combined with cognitive training is a safe and effective modality for the treatment of Alzheimer’s disease: A randomized, double-blind study. J. Neural Transm. 2013 120 5 813 819 10.1007/s00702‑012‑0902‑z 23076723
    [Google Scholar]
  51. Turriziani P. Smirni D. Mangano G.R. Low-frequency repetitive transcranial magnetic stimulation of the right dorsolateral prefrontal cortex enhances recognition memory in alzheimer’s disease. J. Alzheimers Dis. 2019 72 2 613 622 10.3233/JAD‑190888 31609693
    [Google Scholar]
  52. Cui H. Ren R. Lin G. Repetitive transcranial magnetic stimulation induced hypoconnectivity within the default mode network yields cognitive improvements in amnestic mild cognitive impairment: A randomized controlled study. J. Alzheimers Dis. 2019 69 4 1137 1151 10.3233/JAD‑181296 31127779
    [Google Scholar]
  53. Bashir S. Uzair M. Abualait T. Effects of transcranial magnetic stimulation on neurobiological changes in Alzheimer’s disease. Mol. Med. Rep. 2022 25 4 109 10.3892/mmr.2022.12625 35119081
    [Google Scholar]
  54. Xu X. Xu M. Su Y. Efficacy of repetitive transcranial magnetic stimulation (rTMS) combined with psychological interventions: A systematic review and meta-analysis of randomized controlled trials. Brain Sci. 2023 13 12 1665 10.3390/brainsci13121665 38137113
    [Google Scholar]
  55. Liu G. Xue B. Guan Y. Luo X. Effects of repetitive transcranial magnetic stimulation combined with cognitive training on cognitive function in patients with Alzheimer’s disease: A systematic review and meta-analysis. Front. Aging Neurosci. 2024 15 1254523 10.3389/fnagi.2023.1254523 38332809
    [Google Scholar]
  56. Guse B. Falkai P. Wobrock T. Cognitive effects of high-frequency repetitive transcranial magnetic stimulation: A systematic review. J. Neural Transm. (Vienna) 2010 117 1 105 122 10.1007/s00702‑009‑0333‑7 19859782
    [Google Scholar]
  57. Ngandu T. Lehtisalo J. Solomon A. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): A randomised controlled trial. Lancet 2015 385 9984 2255 2263 10.1016/S0140‑6736(15)60461‑5 25771249
    [Google Scholar]
  58. Gregory S.T. Goodman W.K. Kay B. Riemann B. Storch E.A. Cost-effectiveness analysis of deep transcranial magnetic stimulation relative to evidence-based strategies for treatment-refractory obsessive-compulsive disorder. J. Psychiatr. Res. 2022 146 50 54 10.1016/j.jpsychires.2021.12.034 34953305
    [Google Scholar]
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Repetitive Transcranial Magnetic Stimulation in Dementia
Bentham Science Publishers ; https://doi.org/10.2174/0118746098392580251003064940
/content/journals/cas/10.2174/0118746098392580251003064940
/content/journals/cas/10.2174/0118746098392580251003064940
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  • Article Type:     Review Article
Keywords: neuromodulation ; mild cognitive impairment ; non-invasive brain stimulation ; Alzheimer’s disease ; repetitive transcranial magnetic stimulation ; cognitive dysfunction ; dementia ; synaptic modulation ; neuroplasticity

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