An overview of repetitive transcranial magnetic stimulation (rTMS) in Alzheimer’s disease

Ruth Alcalá Lozano, Erik Daniel Morelos Santana, Orely Osorio Rojas, Jorge Julio González



Background. Alzheimer’s disease (AD) is the most frequent neurocognitive disorder. It affects 50% to 75% of the cases of dementia, and is characterized by a progressive cognitive decline that hinders behavior and functionality. Its etiology is still uncertain, and the efficiency of treatments is limited. Repetitive transcranial magnetic stimulation (rTMS) has been used as an alternative therapeutic strategy, but the clinical impact on Alzheimer’s disease has hardly been studied.

Objective. To describe the effects of rTMS on cognition, the behavioral and psychological symptoms of dementia (BPSD), and functionality, considering the various modes of application.

Method. The PubMed, ScienceDirect, and PsycInfo databases were consulted using key words relating to the topic of study. Articles published between 2006 and 2016 were selected.

Results. The studies that have assessed the clinical effect of rTMS have used various parameters to stimulate and compare the different cortical areas, principally the dorsolateral prefrontal cortex. A variety of benefits have been proposed for patients with Alzheimer’s disease in cognitive domains such as language and episodic memory, as well as behavior and functionality in everyday activities.

Discussion and conclusion. rTMS has been suggested as a possible treatment for AD, and the results indicate the need for further studies with different methodological designs and more participants, in addition to cognitive rehabilitation techniques. The objective is to identify the most efficient parameters for stimulation and to explore new cortical targets.


Alzheimer’s disease; repetitive transcranial magnetic stimulation; cognition

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Ahmed, M. A., Darwish, E. S., Khedr, E. M., El Serogy, Y. M., & Ali, A. M. (2012). Effects of low versus high frequencies of repetitive transcranial magnetic stimulation on cognitive function and cortical excitability in Alzheimer’s dementia. J Neurol, 259(1), 83–92.

Alzheimer’s Association. (2015). 2015 Alzheimer’s disease facts and figures. Alzheimer’s & Dementia : Alzheimers Dement, 11(3), 332–84.

Anderkova, L., & Rektorova, I. (2014). Cognitive effects of repetitive transcranial magnetic stimulation in patients with neurodegenerative diseases - Clinician’s perspective . Neurol Sci , 339(1–2), 15–25.

Barnes, D. E., & Yaffe, K. (2011). The projected effect of risk factor reduction on Alzheimer’s disease prevalence. The Lancet Neurol, 10(9), 819–828.

Bentwich, J., Dobronevsky, E., Aichenbaum, S., Shorer, R., Peretz, R., Khaigrekht, M., … Rabey, J. M. (2011). Beneficial effect of repetitive transcranial magnetic stimulation combined with cognitive training for the treatment of Alzheimer’s disease: a proof of concept study. J Neurla Trasm (Vienna, Austria : 1996), 118(3), 463–471.

Boggio, P. S., Valasek, C. A., Campanhã, C., Giglio, A. C. A., Baptista, N. I., Lapenta, O. M., & Fregni, F. (2011). Non-invasive brain stimulation to assess and modulate neuroplasticity in Alzheimer’s disease. Neuropsychol Rehabil, 21(5), 703–716.

Brem, A.-K., Schilberg, L., Freitas, C., Atkinson, N., Seligson, E., & Pascual-Leone, A. (2013). Effects of cognitive training and rTMS in Alzheimer’s disease. Alzheimer’s & Dementia, 9(4, Supplement), P664.

Cotelli, M., Calabria, M., Manenti, R., Rosini, S., Zanetti, O., Cappa, S. F., & Miniussi, C. (2011). Improved language performance in Alzheimer disease following brain stimulation. J Neurol Neurosurg Psychiatry, 82(7), 794–797.

Cotelli, M., Manenti, R., Cappa, S. F., Geroldi, C., Zanetti, O., Rossini, P. M., & Miniussi, C. (2006). Effect of transcranial magnetic stimulation on action naming in patients with Alzheimer disease. Arch Neurol, 63(11), 1602–1604.

Cotelli, M., Manenti, R., Cappa, S. F., Zanetti, O., & Miniussi, C. (2008). Transcranial magnetic stimulation improves naming in Alzheimer disease patients at different stages of cognitive decline. Eur J Neurol, 15(12), 1286–1292.

Cotelli, M., Manenti, R., Zanetti, O., & Miniussi, C. (2012). Non-pharmacological intervention for memory decline. Front in Hum Neurosci, 6(March), 46.

Devi, G., Voss, H. U., Levine, D., Abrassart, D., Heier, L., Halper, J., … Lowe, S. (2014). Open-label, short-term, repetitive transcranial magnetic stimulation in patients with Alzheimer’s disease with functional imaging correlates and literature review. Am J of Alzheimers Dis Other Demen, 29(3), 248–255.

Dubois, B., Feldman, H. H., Jacova, C., Cummings, J. L., DeKosky, S. T., Barberger-Gateau, P., … Scheltens, P. (2010). Revising the definition of Alzheimer’s disease: a new lexicon. The Lancet Neurol, 9(11), 1118–1127.

Dubois, B., Hampel, H., Feldman, H. H., Scheltens, P., Aisen, P., Andrieu, S., … Working, I. (2016). Preclinical Alzheimer ’ s disease : Definition , natural history , and diagnostic criteria Elsevier Inc (Vol. 12).

Edmund S. Higgins, M. S. G. (2008). Brain Stimulation Therapies for the Clinician. Am Psychiatr Publ.

Fitzgerald, P. B., & Daskalakis, Z. J. (2013). Repetitive Transcranial Magnetic Stimulation Treatment for Depressive Disorders A Practical Guide. Springer

Fonseca, L. M., Navatta, A. C. R., Bottino, C. M. C., & Miotto, E. C. (2015). Cognitive Rehabilitation of Dementia in Adults with Down Syndrome: A Review of Non-Pharmacological Interventions. Demet Geriatr Cogn Dis Extra, 5(3), 330–340.

Freitas, C., Mondragón-Llorca, H., & Pascual-Leone, A. (2011). Noninvasive brain stimulation in Alzheimer’s disease: Systematic review and perspectives for the future. Exp Gerontol, 46(8), 611–627.

Guse, B., Falkai, P., & Wobrock, T. (2010). Cognitive effects of high-frequency repetitive transcranial magnetic stimulation: A systematic review. J of Neural Transm, 117(1), 105–122.

Haffen, E., Chopard, G., Pretalli, J. B., Magnin, E., Nicolier, M., Monnin, J., … Vandel, P. (2012). A case report of daily left prefrontal repetitive transcranial magnetic stimulation (rTMS) as an adjunctive treatment for Alzheimer disease. Brain Stimul, 5(3), 264–266.

Hsu, W.-Y., Ku, Y., Zanto, T. P., & Gazzaley, A. (2015). Effects of noninvasive brain stimulation on cognitive function in healthy aging and Alzheimer’s disease: a systematic review and meta-analysis. Neurobiol. Aging, 36(8), 2348–59.

Innocenti, I., Giovannelli, F., Cincotta, M., Feurra, M., Polizzotto, N. R., Bianco, G., … Rossi, S. (2010). Event-related rTMS at encoding affects differently deep and shallow memory traces. NeuroImage, 53(1), 325–330.

Lee, J., Choi, B. H., Oh, E., Sohn, E. H., & Lee, A. Y. (2016).

Treatment of Alzheimer’s Disease with Repetitive Transcranial Magnetic Stimulation Combined with Cognitive Training: A Prospective, Randomized, Double-Blind, Placebo-Controlled Study. J Clin Neurol (Seoul, Korea).

Lefaucheur, J.-P., Andre-Obadia, N., Antal, A., Ayache, S. S., Baeken, C., Benninger, D. H., … Garcia-Larrea, L. (2014). Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). Clin Neurophysiol, 125(11), 2150–2206.

Loo, C. K. (2002). Applications of transcranial magnetic stimulation (TMS) in psychiatry. J ECT, 18(1), 62.

Luber B, Kinnunen LH, Rakitin BC, Ellsasser R, Stern Y, L. S. (2007). Facilitation of performance in a working memory task with rTMS stimulation of the precuneus: frequency-and time-dependent effects. Brain Res Cogn Brain Res, 1128, 120–9.

Manenti, R., Cotelli, M., Robertson, I. H., & Miniussi, C. (2012). Transcranial brain stimulation studies of episodic memory in young adults, elderly adults and individuals with memory dysfunction: A review. Brain Stimul, 5(2), 103–109.

McKhann, G. M., Knopman, D. S., Chertkow, H., Hyman, B. T., Jack, C. R., Kawas, C. H., … Phelps, C. H. (2011). The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s and Dementia, 7(3), 263–269.

Miniussi, C., & Ruzzoli, M. (2013). Transcranial stimulation and cognition. Handbook of Clinical Neurology, 116, 739–750.

Nardone, R., Bergmann, J., Christova, M., Caleri, F., Tezzon, F., Ladurner, G., … Golaszewski, S. (2012). Effect of transcranial brain stimulation for the treatment of Alzheimer disease: A review. Int J Alzheimers Dis, 2012.

Nardone, R., Tezzon, F., Höller, Y., Golaszewski, S., Trinka, E., & Brigo, F. (2014). Transcranial magnetic stimulation (TMS)/repetitive TMS in mild cognitive impairment and Alzheimer’s disease. Acta Neurol Scand, 129(6), 351–366.

NICE. (2014). Rivastigmine and memantine for the treatment of Alzheimer ’s disease, (April).

OMS y Alzheimer’s Disease International (ADI). (2013). Dementia: a public health priority. Demencia.

Palomo, R. (2015). Guía de consulta de los Criterios diagnósticos del DSM-5. (A. P. ASSOCIATION, Ed.).

Pascual-Leone, A. (2011). Transcranial magnetic stimulation in cognitive rehabilitation. Neuropsychol Rehabil, 21(5), 579–601.

Prince, M., Albanese, E., Guerchet, M., & Prina, M. (2014). Alzheimer’s Disease International. Dementia and risk reduction: an analysis of protective and modifiable factors. Alzheimer’s Disease International, 1–104.

Prince, M., Wimo, A., Guerchet, M., Gemma-Claire, A., Wu, Y.-T., & Prina, M. (2015). World Alzheimer Report 2015: The Global Impact of Dementia - An analysis of prevalence, incidence, cost and trends. Alzheimer’s Disease International, 84.

Rabey, J. M., Dobronevsky, E., Aichenbaum, S., Gonen, O., Marton, R. G., & Khaigrekht, M. (2013). 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, 120(5), 813–819.

Reitz, C., & Mayeux, R. (2014). Alzheimer disease: Epidemiology, Diagnostic Criteria, Rist Factors and Biomarkers. Biochem Pharmacol., 88(4), 640–651.

Rossi, S., Hallett, M., Rossini, P. M., Pascual-Leone, A., Avanzini, G., Bestmann, S., … Ziemann, U. (2009). Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol, 120(12), 2008–2039.

RotenbergWolfgang, A. (2014). Transcranial Magnetic Stimulation Series Editor.

Rutherford, G., Gole, R., & Moussavi, Z. (2013). rTMS as a Treatment of Alzheimer ’ s Disease with and without Comorbidity of Depression : A Review. Neurosci J, 2013, 5.

Scheltens, P., Blennow, K., Breteler, M. M. B., Strooper, B. De, Frisoni, G. B., Salloway, S., & Flier, W. M. Van Der. (2016). Seminar Alzheimer ’ s disease, 6736(15), 1–13.

Steinberg, M., Shao, H., Zandi, P., Lyketsos, C. G., Kathleen, A., Norton, M. C., … Joann, T. (2010). Point and 5-year period prevalence of neuropsychiatric symptoms in dementia : the Cache County Study. INT J GEriatr Psychiatry, 23(2), 170–177.

Wu, Y., Xu, W., Liu, X., Xu, Q., Tang, L., & Wu, S. (2015). Adjunctive treatment with high frequency repetitive transcranial magnetic stimulation for the behavioral and psychological symptoms of patients with Alzheimer’s disease: a randomized, double-blind, sham-controlled study. Shanghai Archs Psychiatry, 27(5), 280–8.