Use of Fast Gamma Magnetic Stimulation Over the Left Prefrontal Dorsolateral Cortex for the Treatment of MCI and Mild Alzheimer's Disease: A Double-Blind, Randomized, Sham-Controlled, Pilot Study

Alberto José Mimenza-Alvarado, Sara Gloria Aguilar-Navarro, Francisco M Martinez-Carrillo, Alma E Ríos-Ponce, Gabriel Villafuerte, Alberto José Mimenza-Alvarado, Sara Gloria Aguilar-Navarro, Francisco M Martinez-Carrillo, Alma E Ríos-Ponce, Gabriel Villafuerte

Abstract

Background: Alzheimer's disease (AD) animal models have shown a reduced gamma power in several brain areas, and induction of these oscillations by non-invasive methods has been shown to modify several pathogenic mechanisms of AD. In humans, the application of low-intensity magnetic fields has shown to be able to produce neural entrainment at the magnetic pulse frequency, making it useful to induce gamma frequencies. Objective: The aim of this study was to assess if the application of fast gamma magnetic stimulation (FGMS) over the left prefrontal dorsolateral cortex would be a safe and well-tolerated intervention that could potentially improve cognitive scores in subjects with mild cognitive impairment and mild AD. Methods: In these randomized, double-blind, sham-controlled study, participants were assigned to either receive daily sessions two times a day of active or sham FGMS for 6 months. Afterward, measurements of adverse effects, cognition, functionality, and depression were taken. Results: Thirty-four patients, 17 in each group, were analyzed for the primary outcome. FGMS was adequately tolerated by most of the subjects. Only four patients from the active FGMS group (23.52%) and one patient from the sham FGMS group (5.88%) presented any kind of adverse effects, showing no significant difference between groups. Nevertheless, FGMS did not significantly change cognitive, functionality, or depressive evaluations. Conclusion: FGMS over the left prefrontal dorsolateral cortex applied twice a day for 6 months resulted to be a viable intervention that can be applied safely directly from home without supervision of a healthcare provider. However, no statistically significant changes in cognitive, functionality, or depression scores compared to sham stimulation were observed. Clinical Trial Registration:www.ClinicalTrials.gov, Identifier: NCT03983655, URL: https://ichgcp.net/clinical-trials-registry/NCT03983655.

Keywords: Alzheimer's disease; brain stimulation; fast gamma magnetic stimulation; gamma oscillation; low intensity; mild cognitive impairment.

Conflict of interest statement

The authors declare that GV and AR-P are currently working as part of the Science Department of Actipulse Neuroscience. Actipulse Neuroscience provided the devices and financed this study. Actipulse Neuroscience did not play any role in the study design; collection, analysis, and interpretation of the data; as well as writing of the report and decision to submit the article for publication. The 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 Mimenza-Alvarado, Aguilar-Navarro, Martinez-Carrillo, Ríos-Ponce and Villafuerte.

Figures

Figure 1
Figure 1
Characteristics of FGMS. (A) Pattern of the magnetic field in trains, consisting of 3-s bursts of pulses at fast gamma frequency (125 Hz) alternated with 1-s without stimulation for 450 trains. (B) Pulse pattern delivered.
Figure 2
Figure 2
Diagram of the method from recruitment to analysis. The diagram explains the number of subjects in each step and the population per group.
Figure 3
Figure 3
Changes in secondary outcome scores over time, including all cognitive assessments and depression assessment. (A) Comparison of ADAS-Cog score at baseline and after 6 months of treatment. (B) Comparison of MoCA scores at baseline and after 6 months of treatment. (C) Comparison of FAB scores at baseline and after 6 months of treatment. (D) Comparison of pVFT scores at baseline and after 6 months of treatment. (E) Comparison of sVFT scores at baseline and after 6 months of treatment. (F) Comparison of GDS-15 scores at baseline and after 6 months of treatment.

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