Effects of gamma sensory stimulation on cognitive function in Alzheimer’s disease patients

Abstract

AbstractBackgroundAlzheimer’s disease (AD) patients exhibit distorted excitatory‐inhibitory balance of neuronal activity, leading to accelerated worsening of functional and cognitive abilities. Improving abnormal neuronal synchrony by long‐term non‐invasive, gamma sensory stimulation at 40 Hz in transgenic mice carrying pathological AD human genes has been shown to beneficially affect neural activity and improve learning and memory. In the present translational clinical trial, the effects of gamma sensory stimulation on cognition and global function were evaluated in AD patients using an at‐home therapy device (Cognito Therapeutics, Cambridge, MA).MethodThe phase I/II randomized, controlled, single‐blinded multi‐center clinical trial (Overture study; NCT03556280) evaluated safety, adherence rates and efficacy of gamma sensory stimulation therapy in patients with mild to moderate Alzheimer’s disease (MMSE 14‐26, inclusive). The 6‐month trial included treatment and sham groups receiving daily, one‐hour sensory stimulation but only participants in the treatment group were exposed to 40Hz auditory and visual stimulations. During the trial, cognitive functions were measured by Alzheimer's Disease Assessment Scale (ADAS‐Cog), Mini‐Mental State Examination (MMSE), and Clinical Dementia Rating Sum of Boxes (CDR‐SB). In order to align assessment data in time to study events (therapy start and end) and account for variable study visit intervals at start and end of therapy period, cognitive measures were calculated on a per‐patient basis by a model of AD‐related cognitive decline derived from a large‐scale dataset. Finally, adjusted cognitive scores were compared between the two groups.ResultThe trial has been completed by 33 and 19 patients in the treatment and sham groups, respectively. Daily therapy of gamma sensory stimulation was well tolerated, confirming safety and high adherence. The three independent cognitive tests demonstrated a diminished cognitive decline in the treatment group compared to the sham group. Final analysis results from MMSE, ADAS‐Cog, CDR‐SB and Integrated Alzheimer's Disease Rating Scale (iADRS) will be presented at the meeting.ConclusionThe present findings, together with the established safety profile, functional benefit, and improvement in sleep justify further evaluation of gamma sensory stimulation in AD patients.