Gamma‐Frequency Sensory Stimulation is Safe and Well‐Tolerated Treatment Option for Patients with Alzheimer’s Disease

• Published in: Alzheimer's & dementia Vol. 18; no. S8
• Main Authors: Hajos, Mihaly, Boasso, Alyssa, Hempel, Evan, Cimenser, Aylin, Seshagiri, Chandran, Megerian, Jonathan Thomas, Vaughan, Brent, Malchano, Zach
• Format: Journal Article
• Language: English
• Published: 01.12.2022
• DOI: 10.1002/alz.064296
• ISSN: 1552-5260

Background Recent experimental findings demonstrate that sensory‐evoked brain gamma oscillation reduces Alzheimer’s disease (AD) pathologies in AD‐related transgenic mice, including decline in synaptic function, neurodegeneration, and brain atrophy (Adaikkan & Tsai, Trends Neurosci. 2020;43:24‐41). Based on these findings, gamma‐frequency sensory stimulation has been evaluated in multiple clinical trials, including the long‐term Overture a randomized, controlled trial (Clinicaltrials.gov: NCT03556280) assessing safety, tolerance, and efficacy of using Cognito Therapeutics medical device in patients with AD. Method Patients with clinical presentation of AD spectrum (MMSE 14‐26, inclusive) were randomized 2:1 to receive daily, one‐hour, EEG‐calibrated, 40Hz noninvasive audio‐visual stimulation or sham stimulation over a 6‐month period. Therapy was self‐administered at home with the help of a care partner. Safety was evaluated by magnetic resonance imaging (MRI), physical and neurological exams at baseline, 12‐, and 24‐weeks, and monthly assessments of adverse events (AEs). Tolerability was measured by device use data, daily diary, and user experience interviews. Result A total of 135 subjects were screened, of whom 74 (55%) were randomized and 53 completed (72%). The safety population included all subjects who performed at least one day of treatment. During the 6‐month (168 days) treatment period, both groups completed daily therapies at a similar rate (147 active vs 139 sham). Treatment‐related AEs occurred in 19 subjects (41.3%) in the active treatment group and 8 subjects (28.6%) in the sham group. The incidence of treatment‐related AEs was similar between treatment groups except for headache (21.7% active group vs 10.7% sham group) and tinnitus (15.2% active group vs 0% sham group). All treatment‐related AEs were mild in intensity except tinnitus and anxiety (1 active group subject) and agitation (1 sham group subject) which were considered moderate. Review of MRI data demonstrated absence of ARIA in all subjects. High adherence rates (over 83%) were observed in both sham and treatment subjects; 60% of enrolled participants entered open label extension. Conclusion Gamma‐frequency sensory stimulation is safe and well tolerated by trial participants. Together with efficacy shown on functional and cognitive abilities and brain atrophy (Hajós et al., JPAD 2021;8:S60‐61), gamma‐frequency sensory stimulation can be considered as viable treatment option for patients with AD.