Randomized controlled trial of gamma sensory stimulation treatment maintains functional ability and decreases sleep fragmentation in Alzheimer’s disease patients

Abstract

AbstractBackgroundDaily, at‐home gamma sensory stimulation consisting of EEG‐calibrated auditory and visual stimuli is a new therapeutic approach for the treatment of Alzheimer’s Disease (AD). Based on experimental studies demonstrating that sensory‐evoked gamma oscillation halts or reverses AD‐related pathology, improves cognitive function, and normalizes circadian rhythm in transgenic mice carrying human AD pathological genes, this clinical trial evaluated the effects of 40Hz sensory stimulation on functional ability and sleep quality of AD patients.MethodPatients with mild‐to‐moderate AD (MMSE 14‐26, inclusive; n=74) were randomized to receive either 40Hz noninvasive audio‐visual stimulation or sham stimulation over a 6‐month period. Functional abilities of patients were measured by Alzheimer's Disease Cooperative Study ‐ Activities of Daily Living (ADCS‐ADL) scale at baseline and every four weeks during the study and follow‐up period. Sleep quality was assessed from nighttime activities of a subgroup of patients (n=7 in treatment, n=6 in sham groups) who were monitored continuously via a wrist worn actigraphy watch throughout the 6‐month period.ResultAdjusted ADCS‐ADL scores from beginning and end of the trial were compared in patients who completed the trial. Over the 6‐month period, patients in the sham group (n=19) showed the expected decline, a 5.40‐point drop in ADCS‐ADL scores, whereas patients in the treatment group (n=33) receiving therapy exhibited only a 0.57‐point decline. Changes in ADCS‐ADL scores were statistically significant between the sham and treatment groups (P<0.01). Nighttime active durations in the treatment group were significantly (p<0.03) reduced in the second 3 months compared to the first 3 months but the opposite change was observed in the sham group. After normalizing the active durations by the corresponding nighttime period of each patient, the analysis confirmed opposite changes in nighttime active durations between the two groups (p<0.001).ConclusionPatients in gamma sensory stimulation therapy maintained their activities of daily living and showed an improved sleep quality over a 6‐month treatment period; two outcome measures, functional ability and sleep quality known to be strongly linked in AD. Maintenance of functional ability represents an important treatment and management goal for AD patients, reducing formal and informal care, and delaying time to institutionalization.