Dementias - Original Article

Journal of Neural Transmission

, Volume 118, Issue 3, pp 463-471

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

  • Jonathan BentwichAffiliated withNeuronix Ltd
  • , Evgenia DobronevskyAffiliated withDepartment of Neurology, Assaf Harofeh Medical Center, The Sackler Faculty of Medicine, Tel Aviv UniversityMemory Clinic, Assaf Harofeh Medical Center, The Sackler Faculty of Medicine, Tel Aviv University
  • , Sergio AichenbaumAffiliated withDepartment of Neurology, Assaf Harofeh Medical Center, The Sackler Faculty of Medicine, Tel Aviv University
  • , Ran ShorerAffiliated withMemory Clinic, Assaf Harofeh Medical Center, The Sackler Faculty of Medicine, Tel Aviv University
  • , Ruth PeretzAffiliated withMemory Clinic, Assaf Harofeh Medical Center, The Sackler Faculty of Medicine, Tel Aviv University
  • , Michael KhaigrekhtAffiliated withMemory Clinic, Assaf Harofeh Medical Center, The Sackler Faculty of Medicine, Tel Aviv University
  • , Revital Gandelman MartonAffiliated withDepartment of Neurology, Assaf Harofeh Medical Center, The Sackler Faculty of Medicine, Tel Aviv University
  • , Jose M. RabeyAffiliated withDepartment of Neurology, Assaf Harofeh Medical Center, The Sackler Faculty of Medicine, Tel Aviv UniversityMemory Clinic, Assaf Harofeh Medical Center, The Sackler Faculty of Medicine, Tel Aviv University Email author 

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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.

Keywords

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