Dysregulated gamma brain oscillations are a hallmark of Alzheimer's disease (AD). A new noninvasive method of brain stimulation called transcranial alternating current stimulation (tACS) can entrain cerebral oscillations at certain frequencies. To evaluate the safety, practicality, and effectiveness of home-based gamma tACS administered over the precuneus in patients with prodromal and mild AD, this study was carried out.
From December 10, 2022, to October 15, 2024, a tertiary AD research clinic in Italy hosted this randomized, double-blind, sham-controlled clinical study with an open-label extension phase. Participants have to be diagnosed with AD. For eight weeks, participants were randomly assigned to receive either sham stimulation or home-based gamma tACS (5 sessions per week, lasting 60 minutes each) (double-blind phase). After that, gamma tACS was administered to all subjects for an extra eight weeks (open-label phase) and an 8-week follow-up.
Clinical effectiveness, safety, and feasibility were the main goals. Measures of biological effectiveness, such as gamma band power measured by electroencephalography, cholinergic neurotransmission, AD plasma biomarker levels, and brain connectivity measured by magnetic resonance imaging, were secondary end goals.
50 of the 60 screened individuals with prodromal or moderate Alzheimer disease (mean age 67 years) were randomly assigned to either gamma or sham tACS. Gamma tACS administered at home was well-tolerated and safe. When compared to a sham, it significantly improved associative memory, everyday functioning, and global cognition.
Only in the gamma tACS group did neurophysiological tests reveal increased gamma power and cholinergic transmission.There was no change in plasma biomarkers. After 8 weeks, benefits peaked, and continuing therapy for an additional 16 weeks had no additional impact. Overall, the results of this randomized clinical trial indicate that gamma tACS over the precuneus is a viable strategy for improving cognitive performance and modifying neurophysiological abnormalities in AD and may be performed safely and successfully in a home-based context.
Source:
Cantoni, V., Casula, E. P., Tarantino, B., Cupidi, C., Huber, N., Altomare, D., Premi, E., Zummo, E., Esposito, R., Leonardi, C., Herukka, S.-K., Solje, E., Ferrari, A., Cotelli, M. S., Gasparotti, R., Martorana, A., Fracassi, C., Santarnecchi, E., Koch, G., … Borroni, B. (2025). Home-based gamma transcranial alternating current stimulation in patients with Alzheimer disease: A randomized clinical trial: A randomized clinical trial. JAMA Network Open, 8(12), e2546556. https://doi.org/10.1001/jamanetworkopen.2025.46556
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