Beneficial effect of repetitive transcranial magnetic stimulation combined with cognitive training for the treatment of Alzheimer’s disease: a proof of concept study
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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.
KeywordsrTMS 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.
- Birks J (2006) Cholinesterase inhibitors for Alzheimer’s disease. Cochrane Database Syst Rev 1:CD005593. doi: 10.1002/14651858.CD005593
- Birks J, Grimley Evans J, Iakovidou V, Tsolaki M, Holt FE (2009) Rivastigmine for Alzheimer’s disease. Cochrane Database Syst Rev 2:CD001191. doi: 10.1002/14651858.CD001191.pub2
- Foerster S, Buschert VC, Buchholz HG, Teipel SJ, Zach C, Bartenstein P, Buerger K (2009) Positive effects of a 6-month stage-specific cognitive intervention program on brain metabolism in subjects with amnestic mild cognitive impairment (aMCI) and mild Alzheimer’s Disease (AD). Alzheimers Dementia 5(4 Suppl 1):38CrossRefGoogle Scholar
- Fratiglioni L, Launer LJ, Andersen K, Breteler MM, Copeland JR, Lobo A, Martinez-Lage J, Soininen H, Hofman A (2000) Incidence of dementia and major subtypes in Europe: A collaborative study of population-based cohorts. Neurol Dis Elderly Res Group 54(11 Suppl 5):S10–15Google Scholar
- George MS, Lisanby SH, Avery D, McDonald WM, Durkalski V, Pavlicova M, Anderson B, Nahas Z, Bulow P, Zarkowski P, Holtzheimer PE 3rd, Schwartz T, Sackeim HA (2010) Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder: a sham-controlled randomized trial. Arch General Psychiatr 67(5):507–516CrossRefGoogle Scholar
- Guy W (1976) Clinical global impressions. In: ECDEU assessment manual for psychopharmacology, revised (DHEW Publ No ADM 76–338). National Institute of Mental Health, Rockville, pp 218–222Google Scholar
- Hamilton M (1980) Rating depressive patients. J Clin Psychiatr 41(12 Pt 2):21–24Google Scholar
- Kimbrell TA, Little JT, Dunn RT, Frye MA, Greenberg BD, Wassermann EM, Repella JD, Danielson AL, Willis MW, Benson BE, Speer AM, Osuch E, George MS, Post RM (1999) Frequency dependence of antidepressant response to left prefrontal repetitive transcranial magnetic stimulation (rTMS) as a function of baseline cerebral glucose metabolism. Biol Psychiatr 46(12):1603–1613CrossRefGoogle Scholar
- Mantovani A, Lisanby SH (2004) Applications of transcranial magnetic stimulation to therapy in psychiatry. Psychiatr Times 21(9)Google Scholar
- Mecocci P, Bladstrom A, Stender K (2009) Effects of memantine on cognition in patients with moderate to severe Alzheimer’s disease: post-hoc analyses of ADAS-cog and SIB total and single-item scores from six randomized, double-blind, placebo-controlled studies. Int J Geriatr Psychiatr 24(5):532–538CrossRefGoogle Scholar
- Plassman BL, Langa KM, Fisher GG, Heeringa SG, Weir DR, Ofstedal MB, Burke JR, Hurd MD, Potter GG, Rodgers WL, Steffens DX, Willis RJ, Wallace RB (2007) Prevalence of dementia in the United States: the aging, demographics, and memory study. Neuroepidemiology 29(1–2):125–132PubMedCrossRefGoogle Scholar
- Tárraga L, Boada M, Modinos G, Espinosa A, Diego S, Morera A, Guitart M, Balcells J, Lopez OL, Becker JT (2006) A randomised pilot study to assess the efficacy of an interactive, multimedia tool of cognitive stimulation in Alzheimer’s disease. J Neurol Neurosurg Psychiatr 77(10):1116–1121PubMedCrossRefGoogle Scholar