Improved cognitive function following treatment of alzheimers patients with repetitive transcranial magnetic stimulation (rTMS) interlaced with

cognitive training
Lukas Schilberg, Anna-Katharine Brem, Catarina Freitas, Natasha Atkinson Leonie Asboth, Christina Carbone, Ilya Vidrin, Alvaro Pascual-Leone Beth Israel Deaconess Medical Center, Harvard Medical School; Berenson-Allen Center for Noninvasive Brain Stimulation.

Introduction
Alzheimers Disease (AD) is the most common cause of dementia. During the pathological course the brain undergoes drastic changes including brain atrophy and synaptic plasticity impairments. The primary symptoms are memory loss and a general cognitive decline. Transcranial Magnetic Stimulation (TMS) can be used to modulate brain plasticity and may enhance the effects of cognitive intervention methods when administered in combination. In this study we interleaved rTMS and cognitive training by applying NeuroAD using NICE technology (Neuronix Ltd., Israel) to patients with mild AD. The results suggest a beneficial impact of NeuroAD therapy for cognitive functions as well as for brain plasticity mechanisms. measures showed a striking increase for the NICE treatment group, but not for the sham group (Fig.2).

Conclusion
The NICE treatment demonstrates a beneficial effect on cognitive functions as well as on brain plasticity in patients with mild AD.

Methods
Cognitive functions and cortical plasticity were evaluated and compared before and after a six-week (30 days) period of NICE treatment. Cognitive functions were assessed with the Alzheimers Disease Assessment Scale (ADASCog) and cortical plasticity was measured by the effect of intermittent theta-burst stimulation (iTBS) on the amplitude of motor evoked potentials (MEP). The cognitive training was interleaved with the rTMS administration. During each treatment session 3 out of 6 brain regions (right and left dorsolateral prefrontal cortex, right and left parietal cortex, left superior temporal gyrus, and left inferior frontal gyrus) were stimulated with repetitive Transcranial Magnetic Stimulation (rTMS). The stimulation for each brain region was performed at 120% resting motor threshold and consisted of 20 stimulation trains with 21 pulses at 10Hz. Cognitive tasks were presented on a touch screen computer and were matched to the specific brain regions. A control group of AD patients received sham rTMS and sham cognitive training.
ADAS-Cog Change

-2

AD real group
-4

AD sham group

Figure1. ADAS-Cog change of score (before vs. after NeuroAD intervention) in the real and sham AD group.

% change of MEP amplitude

150

100 AD post iTBS before training 50 AD post iTBS after training AD post iTBS 0 -50 Time after iTBS (min) 20 40 60 80

Results
AD patients who received the NICE treatment improved in the ADAS-cog by -2.08 points, whereas AD patients in the sham group decreased by 2.65 points (Fig.1). The difference between the two groups in the ADAS-cog scores after the NICE-treatment was 4.73 points and was therefore clinically meaningful. Furthermore, brain plasticity

Figure2. Brain plasticity measures in healthy controls and in AD patients before and after NeuroAD intervention.

AAIC, vancover, 2012