Repetitive Transcranial Magnetic Stimulation With H-Coil in Alzheimer's Disease: A Double-Blind, Placebo-Controlled Pilot Study

Letizia Leocani, Gloria Dalla Costa, Elisabetta Coppi, Roberto Santangelo, Marco Pisa, Laura Ferrari, Maria Paola Bernasconi, Monica Falautano, Abraham Zangen, Giuseppe Magnani, Giancarlo Comi, Letizia Leocani, Gloria Dalla Costa, Elisabetta Coppi, Roberto Santangelo, Marco Pisa, Laura Ferrari, Maria Paola Bernasconi, Monica Falautano, Abraham Zangen, Giuseppe Magnani, Giancarlo Comi

Abstract

Focal repetitive transcranial magnetic stimulation (rTMS) has been applied to improve cognition in Alzheimer's disease (AD) with conflicting results. We applied rTMS in AD in a pilot placebo-controlled study using the H2-coil. H-coils are suitable for targeting wider neuronal structures compared with standard focal coils, in particular the H2-coil stimulates simultaneously the frontal-parietal-temporal lobes bilaterally. Thirty patients (mean age 70.9 year, SD 8.1; mean MMSE score 16.9, SD 5.5) were randomized to sham or real 10 Hz rTMS stimulation with the H2-coil. Each patient underwent 3 sessions/week for 4 weeks, followed by 4 weeks with maintenance treatment (1 session/week). Primary outcome was improvement of ADAS-cog at 4 and 8 weeks compared with baseline. A trend toward an improved ADAS-cog score over time was observed for patients undergoing real rTMS, with actively treated patients experiencing a mean decrease of -1.01 points at the ADAS-Cog scale score per time point (95% CIs -0.02 to -3.13, p < 0.04). This trend was no longer evident 2 months after the end of treatment. Real rTMS showed no significant effect on MMSE and BDI changes over time. These preliminary findings suggest that rTMS with H-coil is feasible and safe in patients with probable AD and might provide beneficial, even though transient, effects on cognition. This study prompts larger studies in the early stages of AD, combining rTMS and cognitive rehabilitation. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT04562506.

Keywords: ADAS-cog; Alzheimer's disease; H-coil; neuromodualtion; repetitive transcranial magnetic stimulation.

Conflict of interest statement

AZ was a key inventor of H-coli and acts as a consultant for Brainsway Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Leocani, Dalla Costa, Coppi, Santangelo, Pisa, Ferrari, Bernasconi, Falautano, Zangen, Magnani and Comi.

Figures

Figure 1
Figure 1
Random effect of time on ADAS-cog scores at an individual level. BLUP, best linear unbiased predictor.
Figure 2
Figure 2
Effect of rTMS on ADAS-cog scores over the treatment period and the observational follow-up. T0 = baseline; T1 = 1 month after randomization; T2 = 2 months after randomization corresponding to the end of treatment; T3 = 4 months after randomization, corresponding to two months after the end of treatment. The figure represents predicted means ± standard errors.

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