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

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://clinicaltrials.gov/ct2/show/NCT03983655.

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