J Neural Transm (Vienna). 2016 Dec;123(12):1449-1455. Epub 2016 Sep 8.

Repetitive transcranial magnetic stimulation (rTMS) combined with cognitive training is a safe and effective modality for the treatment of Alzheimer‘s disease: clinical experience.


Alzheimer‘s disease (AD) is the most common type of dementia among the elderly. Common treatments available and non-pharmacological interventions have their limitations, and new therapeutic approaches are critically needed. Transcranial magnetic stimulation (TMS) is a non-invasive technique that generates an electric current-inducing modulation in cortical excitability. The previous clinical trials showed that combinations of rTMS and cognitive training (rTMS-COG), as provided by the NeuroAD medical device system, offer a novel, safe, and effective method improving mild-to-moderate AD patients. In this article, we present our experience with rTMS-COG treatment, in clinical settings, of 30 mild-to-moderate AD patients that received rTMS-COG commercial treatments in two clinics for 1-h daily sessions, 5 days per week, for 6 weeks (30 sessions). Five patients returned for a second treatment. ADAS-Cog and MMSE scores were measured pre- and post-treatments. The main analyses were conducted on patients who received 1 treatment (n = 30). Data received from the five returning patients were analyzed separately. The effect of rTMS-COG treatment was statistically significant regarding both ADAS-Cog (-2.4 point improvement, PV <0.001) and MMSE (+1.7 points improvement, PV <0.001) scores. About 80 % of patients gained some cognitive improvement following NeuroAD treatment, with more than 60 % improving by more than two points, for a minimum of 9 months. The Neuronix NeuroAD System was shown to be a safe and effective non-invasive modality for cognitive improvement of Alzheimerpatients, with measurable outcomes lasting, in some of them, for up to 1 year, following completion of the 6-week daily intervention course (a carryover effect).


Alzheimer’s Disease Assessment Scale-cognitive; Alzheimer’s disease; Cognitive training; Dementia; Mini–mental state examination; rTMS

Neurobiol Aging. 2015 Aug;36(8):2348-59. doi: 10.1016/j.neurobiolaging.2015.04.016. Epub 2015 May 1.

Effects of noninvasive brain stimulation on cognitive function in healthy aging and Alzheimer‘s disease: a systematic review and meta-analysis.


The study aimed to evaluate the effects of noninvasive brain stimulation on cognitive function in healthy older adults and patients with Alzheimer‘s disease. A comprehensive literature search was performed on noninvasive stimulation studies published from January 1990 to November 2014 in Pubmed and Web of Science. Fourteen articles with a total of 331 participants were identified as studies with healthy older adults, and the mean effect size and 95% confidence interval were estimated. A significant effect size of 0.42 was found for the cognitive outcome. Further subgroup analyses demonstrated more prominent effects for studies delivering the stimulation before the execution of the task and studies applying multiple sessions of stimulation. To assess the effects of stimulation on Alzheimer‘s disease patients, 11 studies with a total of 200 patients were included in the analysis. A significant effect size of 1.35 was found for the cognitive outcomes. Subgroup analyses indicated more pronounced effects for studies applying the stimulation during the execution of the task compared with studies delivering the stimulation before the execution of the task. Noninvasive brain stimulation has a positive effect on cognitive function in physiological and pathological aging.


Aging; Alzheimer‘s disease (AD); Cognitive function; Meta-analysis; Neuronal plasticity; Repetitive transcranial magnetic stimulation (rTMS); Transcranial direct current stimulation (tDCS)

J Alzheimers Dis. 2015;48(2):463-72. doi: 10.3233/JAD-150346.

Repetitive Transcranial Magnetic Stimulation as an Alternative Therapy for Cognitive Impairment in Alzheimer‘s Disease: A Meta-Analysis.



Recent studies have indicated that repetitive transcranial magnetic stimulation (rTMS) could improve cognitive function in people with Alzheimer‘s disease (AD). Yet the results are inconclusive.


This meta-analysis aimed to evaluate recent rTMS studies conducted in mild to moderate AD patients.


PubMed, Embase, MEDLINE databases and Science Direct were searched for studies of rTMS treatment on AD patients with cognitive impairment published before February 2015. The relevant primary outcomes of cognition were extracted from those included studies. A crude standardized mean difference (SMD) with 95% confidence interval (CI) was calculated by using random effect models.


Seven studies with a total of 94 mild to moderate AD patients were included in this meta-analysis. A significant overall rTMStreatment effect on cognition was found for all AD patients (p = 0.0008, SMD = 1.00, 95% CI = 0.41-1.58). Stratification analysis showed that this effect is stimulation frequency- and hemisphere-dependent. High frequency stimulation (>1.0 Hz) (p <  0.05) but not low frequency stimulation (≤1.0 Hz) (p >  0.05) was significantly effective in improving the cognition of AD patients. Further, rTMSstimulation on right dorsolateral prefrontal cortex (DLPFC) and bilateral DLPFC (p <  0.05), but not on the left DLPFC (p >  0.05) was significantly effective in improving cognitive function of AD patients. A significant effect was observed in the rTMS subgroup (p <  0.05), rather than in the rTMS+drug subgroup (p >  0.05).


This meta-analysis supports that high frequency rTMS stimulation on right- or bilateral-DLPFC has significant therapeutic effect on cognitive function in patients with mild to moderate AD. Due to small number of studies included, more well-controlled rTMSstudies should be evaluated in AD patients in the future.


Alzheimer’s disease; meta-analysis; mild to moderate cognitive impairment; repetitive transcranial magnetic stimulation

Brain Res Brain Res Rev. 2002 Feb;38(3):309-27.

Transcranial magnetic stimulation and Parkinson‘s disease.


While motor cortical areas are the main targets of the integrative activity of basal ganglia, their main output consists of the corticospinal system. Transcranial magnetic stimulation (TMS), a relatively new method to investigate corticospinal physiology, has been widely used to assess possible changes secondary to Parkinson‘s disease (PD). The use of single- and paired-pulse TMS, two varieties of the original technique, disclosed multiple functional alterations of the corticospinal pathway. For instance, when the latter was tested at ‘rest’, or in response to somesthetic afferents, it showed excess excitability or reduced inhibition. In turn, during production of a voluntary output, its activation was defective, or inadequately modulated. One major mechanism may be a dysfunction of the interneurons mediating the level of excitation within cortical area 4. For instance, there is a shortening of the so-termed ‘central silent period’, which is a complex, TMS-induced, inhibitory phenomenon possibly mediated by activation of GABA(B) receptors. The so-called ‘short-interval intracortical inhibition’, which is possibly mediated by GABA(A) receptors, is also diminished. Levodopa restores these and other TMS alterations, thus demonstrating that cortical area 4 is sensitive to dopamine modulation. Overall, TMS has provided substantial new pathophysiological insights, which point to a central role of the primary motor cortex in the movement disorder typical of PD. Repetitive (r-)TMS, another form of TMS, has been studied as a treatment for PD motor signs. Although some reports are favorable, others are not, and have raised the problem of appropriate control experiments. Although extremely interesting, the potential therapeutic role of r-TMS in PD needs further evaluation.

Rinsho Shinkeigaku. 1999 Dec;39(12):1264-7.

[Therapeutic effect of repetitive transcranial magnetic stimulation in Parkinson‘s disease].

[Article in Japanese]


The therapeutic effect of repetitive transcranial magnetic stimulation (r-TMS) on clinical performance was studied in 8 patients with Parkinson‘s disease (PD). Seven patients were used as controls and underwent sham stimulation. The modified Hoehn and Yahr (H & Y) Staging Scale, Schwab and England Activities of Daily Living (ADL) Scale and Unified Parkinson‘s Disease Rating Scale (UPDRS) were used to assess changes in clinical performance. Eight patients were assessed prior to and following 3, 6 and 9 months of R-TMS. R-TMS was applied manually 60 times (30 times each side) to the frontal areas using a large circular coil, a pulse intensity of 700 V, and a frequency of 0.2 Hz. Sessions were performed once weekly for 9 months. The 7 control patients showed no differences in clinical symptoms between initial evaluations and evaluations after 3 months of sham R-TMS. In all 8 patients, the modified H & Y staging and UPDRS scores decreased significantly, and the Schwab and England ADL Scale increased significantly after 3, 6 and 9 months of R-TMS therapy. These results suggest that R-TMS is beneficial for the treatment of Parkinsonian symptoms.