Gamma Sensory Stimulation Demonstrates Efficacy in Alzheimer Disease in New Analysis


In addition to demonstrating significant differences in slowing functional decline, those on gamma sensory stimulation also demonstrated a significant reduction in brain atrophy relative to the sham group in the OVERTURE study.

Jonathan Megerian, MD

Jonathan Megerian, MD

After preliminary results from the phase 2 OVERTURE study (NCT03556280) confirmed the safety of Cognito Therapeutics’ at-home gamma sensory stimulation device in patients with Alzheimer disease (AD), new data have uncovered more about the cognitive and functional benefits patients receive from this therapy.1

At 6 months, patients treated with the noninvasive, visual and auditory gamma (40 hz) sensory stimulation demonstrated significantly better changes in Alzheimer’s Disease Cooperative Study–Activities of Daily Living (ADCS-ADL) scores compared with those on sham, indicating a 78% slowing in functional decline (P <.0003). The results, presented at the 2022 American Academy of Neurology (AAN) Annual Meeting, April 2-7, in Seattle, Washington, also showed that the treatment has potential disease-modifying effects, indicated by reductions in brain atrophy.

Lead author Jonathan Megerian, MD, pediatric neurology, Children’s Health Orange County Hospital, and colleagues screened 135 individuals on the AD spectrum, of which 74 were randomized and 53 completed the trial. Patients underwent physical and neurological exams, MRI, and were assessed on efficacy outcomes using AD cognitive and functional instruments and volumetric MRI.

In addition to showing better results on ADCS-ADL than placebo, patients treated with gamma sensory stimulation showed a statistically significant 83% (P <.013) reduction in cognitive decline, represented by scores on Mini-Mental State Examination (MMSE). The 2 treatment groups showed no statistically significant differences on other outcome measures such as modified AD Composite Score (MADCOMS), Alzheimer’s Disease Assessment Scale-14 (ADAS-Cog14), and Clinical Dementia Rating-Sum of Boxes (CDR-SB).

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Using quantitative MRI analysis, investigators identified a significant 72% (P <.01) reduction in brain atrophy in the active treatment group compared with sham. Furthermore, reduced lateral ventricle enlargement and diminished loss in cortical thickness in the occipital cortex was also observed, and no patients demonstrated any presence of amyloid-related imaging abnormalities.

Similar to what was previously reported, gamma sensory stimulation showed a safe profile, with no unexpected serious treatment adverse events (AEs). According to the original data, subjects completed a total of 20,562 sessions with gamma sensory stimulation and had similar rates of AEs regardless of whether on treatment (2.5 per subject) or sham (2.5 per subject). Of the treatment group (n = 46), 30 participants (65%) reported AEs, 3 (7%) reported serious adverse events (SAEs), and 3 (7%) reported treatment emergent SAEs). Of the sham group (n = 28), 23 participants (82%) reported AEs, 3 (11%) reported SAEs, and 1 (4%) reported treatment emergent SAEs. Four participants (9%) from the treatment group discontinued due to AE or SAE, compared to 3 participants (11%) from the sham group.2

Originally announced at the 2021 Alzheimer’s Association International Conference (AAIC), the treatment group had a final mean adherence of 90.2% (±13.3) compared with the sham group, which had a final mean adherence of 90.2% (±9.0). The difference was not significant, according to an independent two-tailed t-test (P = .14). When given the option to participate in a 12-month extension of the study, 60% of the participants opted to enroll.

In subanalysis of this trial, patients (n = 22) who received gamma sensory stimulation showed significantly reduced nighttime active periods, in contrast, to deterioration in sleep quality in those on sham over a 24-week treatment period (both P <.03). The average night-time period was 7.23 hours for the treatment group and 7.64 hours for the sham group. The difference between the second 12-week period and the first 12-week period was in the order only of a couple of minutes. Specifically, the difference was –2.65 minutes for the treatment group and 2.07 minutes for the sham group.3

At the time, Brent Vaughan, MBA, chief executive officer, Cognito Therapeutics, said in a statement, “the improvements we have now reported in nighttime sleep for patients with Alzheimer’s, provide further support for our mechanism of disease modification in this patient population. This is a significant milestone, and we look forward to expanding upon our clinical validation in our pivotal study in Alzheimer’s disease."2

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1. Megerian J, Hajos M, Hempel E, et al. Feasibility, safety, and efficacy of gamma sensory stimulation as a novel therapeutic intervention for Alzheimer disease. Presented at: 2022 AAN Annual Meeting; April 2-7; Seattle, Washington. Abstract 1936
2. Williams M, Cimenser A, Cotter C, et al. Safety, feasibility, and adherence of a daily, in-home gamma sensory stimulation therapy with the Cognito Sensory Stimulation System in Alzheimer’s subjects. Presented at 2021 AAIC Annual Meeting; July 26-29. Abstract 268.
3. Cimenser A, Hempel E, Travers T, et al. Sensory-evoked 40-hz gamma oscillation improves sleep and daily activities in Alzheimer disease patients. Front Syst Neurosci. 2021;15:746859. doi:10.3389/fnsys.2021.746859
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