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Beneficial effect of repetitive transcranial magnetic stimulation combined with cognitive training for the treatment of Alzheimer’s disease: a proof of concept study

  • Dementias - Original Article
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Abstract

The current drug treatment for Alzheimer’s disease (AD) is only partially and temporary effective. Transcranial magnetic stimulation (TMS) is a non-invasive technique that generates an electric current inducing modulation in cortical excitability. In addition, cognitive training (COG) may improve cognitive functions in AD. Our aim was to treat AD patients combining high-frequency repetitive TMS interlaced with COG (rTMS-COG). Eight patients with probable AD, treated for more than 2 months with cholinesterase inhibitors, were subjected to daily rTMS-COG sessions (5/week) for 6 weeks, followed by maintenance sessions (2/week) for an additional 3 months. Six brain regions, located individually by MRI, were stimulated. COG tasks were developed to fit these regions. Primary objectives were average improvement of Alzheimer Disease Assessment Scale-Cognitive (ADAS-cog) and Clinical Global Impression of Change (CGIC) (after 6 weeks and 4.5 months, compared to baseline). Secondary objectives were average improvement of MMSE, ADAS-ADL, Hamilton Depression Scale (HAMILTON) and Neuropsychiatric Inventory (NPI). One patient abandoned the study after 2 months (severe urinary sepsis). ADAS-cog (average) improved by approximately 4 points after both 6 weeks and 4.5 months of treatment (P < 0.01 and P < 0.05) and CGIC by 1.0 and 1.6 points, respectively. MMSE, ADAS-ADL and HAMILTON improved, but without statistical significance. NPI did not change. No side effects were recorded. In this study, rTMS-COG (provided by Neuronix Ltd., Yokneam, Israel) seems a promising effective and safe modality for AD treatment, possibly as good as cholinesterase inhibitors. A European double blind study is underway.

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Acknowledgment

We wish to thank Dr. Moshe Faran PhD for his professional assistance, Dr. Shai Efrati MD for his support, Dr. Ilana Galantner PhD for performing the statistical analysis, Dr. Puzhevsky MD for performing the MRI anatomical determinations, and Dr. Carmiya Weingarten-Baror PhD for drafting the article.

Conflict of interest

Neuronix Ltd, Yokneam, Israel, financially supported this study through the Department of Research of Assaf-Harofeh Medical Center, Israel. Prof. Rabey is a consultant for Neruronix Ltd. He is also Chairman of the Steering Committee for the European multi-center research sponsored by Neuronix Ltd. Jonathan Bentwich was an employee of Neuronix Ltd.

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Authors and Affiliations

  1. Neuronix Ltd, Yokneam, Israel

    Jonathan Bentwich

  2. Department of Neurology, Assaf Harofeh Medical Center, The Sackler Faculty of Medicine, Tel Aviv University, 70300, Zerifin, Israel

    Evgenia Dobronevsky, Sergio Aichenbaum, Revital Gandelman Marton & Jose M. Rabey

  3. Memory Clinic, Assaf Harofeh Medical Center, The Sackler Faculty of Medicine, Tel Aviv University, 70300, Zerifin, Israel

    Evgenia Dobronevsky, Ran Shorer, Ruth Peretz, Michael Khaigrekht & Jose M. Rabey

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  1. Jonathan Bentwich
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  2. Evgenia Dobronevsky
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  8. Jose M. Rabey
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Correspondence to Jose M. Rabey.

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Bentwich, J., Dobronevsky, E., Aichenbaum, S. et al. Beneficial effect of repetitive transcranial magnetic stimulation combined with cognitive training for the treatment of Alzheimer’s disease: a proof of concept study. J Neural Transm 118, 463–471 (2011). https://doi.org/10.1007/s00702-010-0578-1

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