Safety, feasibility, and adherence of a daily, in‐home gamma sensory stimulation therapy with the Cognito Sensory Stimulation System in Alzheimer’s subjects

• DOI: 10.1002/alz.056480
• Publication Date: 2021-12-31T11:30:47Z
• Authors: Martin Williams; Aylin Cimenser; Evan Hempel; Colleen Cotter; Mohinish Shukla; Kevin Jiang; Annie Zhang; Holly Mrozak; Alexandra Konisky; Kim Kwan; Mihaly Hajos; Zach Malchano

AbstractBackgroundNon‐invasive, visual and auditory gamma (40 Hz) sensory stimulation demonstrates clearance of β‐amyloid plaques and tau tangles, and cognition improvement in preclinical AD models (Iaccarino, 2016, Martorell, 2019). A home‐use gamma sensory stimulation device (Cognito Therapeutics, Inc., Cambridge, MA) was developed to evoke gamma oscillations in humans. The long‐term safety and feasibility of this approach has not been previously evaluated in AD subjects.MethodOverture is a prospective 6‐month treatment study in mild‐to‐moderate AD of the Cognito device. Subjects were randomized 2:1, treatment:sham. All subjects underwent in‐clinic EEG to confirm gamma entrainment and calibrate the device. Therapy was self‐administered daily during 1‐hour sessions at home with adherence logged by device. Safety assessments included adverse event (AE) monitoring, MRIs, and physical exams. Subjects and caregivers participated in multiple in‐depth interviews to assess the feasibility of this novel therapy. Subjects had the option to enter a 12‐month extension.ResultIn total, 20,562 treatment sessions have been completed by 74 subjects in the Main and Extension period. Overall rates of AEs during the Main and Extension study periods were roughly equivalent between groups (Active: 2.5/subject, Sham: 2.9/subject). There were no unexpected serious treatment emergent adverse events. Review of MR imaging data by neuroradiology demonstrated stable findings from baseline to follow‐up and absence of ARIA in all subjects. Adherence data showed that Sham participants had a final mean adherence of 95.9%±9.0%, while treatment participants had a final mean adherence of 90.2%±13.3%, and the difference was not significant in an independent‐samples, two‐tailed t‐test (p=0.14). Participants easily adopted and adhered to daily self‐administered therapy, with 60% of enrolled participants choosing to continue into the extension.ConclusionThe interim results of the study demonstrate that long‐term, daily, self‐administered, home‐use of gamma sensory stimulation is both safe and well tolerated in mild‐to‐moderate AD subjects.