Journal of Neural Transmission

, Volume 118, Issue 3, pp 463–471 | Cite as

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

  • Jonathan Bentwich
  • Evgenia Dobronevsky
  • Sergio Aichenbaum
  • Ran Shorer
  • Ruth Peretz
  • Michael Khaigrekht
  • Revital Gandelman Marton
  • Jose M. RabeyEmail author
Dementias - Original Article


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.


rTMS Alzheimer’s disease Cognitive training ADAS-cog ADAS-ADL 



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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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Jonathan Bentwich
    • 1
  • Evgenia Dobronevsky
    • 2
    • 3
  • Sergio Aichenbaum
    • 2
  • Ran Shorer
    • 3
  • Ruth Peretz
    • 3
  • Michael Khaigrekht
    • 3
  • Revital Gandelman Marton
    • 2
  • Jose M. Rabey
    • 2
    • 3
    Email author
  1. 1.Neuronix LtdYokneamIsrael
  2. 2.Department of Neurology, Assaf Harofeh Medical CenterThe Sackler Faculty of Medicine, Tel Aviv UniversityZerifinIsrael
  3. 3.Memory Clinic, Assaf Harofeh Medical CenterThe Sackler Faculty of Medicine, Tel Aviv UniversityZerifinIsrael

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