Repetitive transcranial magnetic stimulation combined with cognitive training is a safe and effective modality for the t
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NEUROLOGY AND PRECLINICAL NEUROLOGICAL STUDIES - ORIGINAL ARTICLE
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 Jose M. Rabey • Evgenia Dobronevsky • Sergio Aichenbaum • Ofer Gonen • Revital Gendelman Marton • Michael Khaigrekht Received: 1 July 2012 / Accepted: 23 September 2012 / Published online: 18 October 2012 Springer-Verlag Wien 2012
Abstract Cortical excitability can be modulated using repetitive transcranial magnetic stimulation (rTMS). Previously, we showed that rTMS combined with cognitive training (rTMS-COG) has positive results in Alzheimer’s disease (AD). The goal of this randomized double-blind, controlled study was to examine the safety and efficacy of rTMS-COG in AD. Fifteen AD patients received 1-h daily rTMS-COG or sham treatment (seven treated, eight placebo), five sessions/ week for 6 weeks, followed by biweekly sessions for 3 months. The primary outcome was improvement of the cognitive score. The secondary outcome included improvement in the Clinical Global Impression of Change (CGIC) and Neuropsychiatric Inventory (NPI). There was an improvement in the average ADAS-cog score of 3.76 points after 6 weeks in the treatment group compared to 0.47 in the placebo group and 3.52 points after 4.5 months of treatment, compared to worsening of 0.38 in the placebo (P = 0.04 and P = 0.05, respectively). There was also an improvement in the average CGIC score of 3.57 (after 6 weeks) and 3.67 points (after 4.5 months), compared to 4.25 and 4.29 in the placebo group (mild worsening) (P = 0.05 and P = 0.05, respectively). NPI improved non-significantly. In summary, J. M. Rabey (&) E. Dobronevsky S. Aichenbaum O. Gonen R. G. Marton Department of Neurology, Assaf Harofeh Medical Center, Zerifin 70300, Israel e-mail: [email protected] J. M. Rabey E. Dobronevsky S. Aichenbaum O. Gonen R. G. Marton M. Khaigrekht The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel M. Khaigrekht Memory Clinic, Assaf Harofeh Medical Center, Zerifin 70300, Israel
the NeuroAD system offers a novel, safe and effective therapy for improving cognitive function in AD. Keywords rTMS Alzheimer’s disease Cognitive training ADAS-cog
Introduction Alzheimer’s disease (AD), the most prevalent cause of dementia in the elderly, is defined both by its clinical features and by its unique pathology. It increases dramatically in both prevalence and incidence after the age of 65, and doubles approximately every 5 years in individuals between 65 and 95 years of age (Rafii et al. 2009). Based on pathological findings of loss of cholinergic transmission (Perry et al. 1977), AD is routinely treated with cholinesterase inhibitors (Birks 2006). A long-term study of the ability of donepezil to improve living disabilities showed that there was no significant benefit compared to the placebo for institutionalization or progression of disability (Courtney et al. 2004). During
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