To evaluate neurophysiological responses to gamma sensory stimulation in Alzheimer’s disease (AD) patients as potential biomarkers for clinical outcomes measuring cognitive and functional abilities and brain atrophy.

Pathological changes in EEG patterns have been considered for detecting early stage of AD and as potential targets for therapeutic intervention. Recent studies have demonstrated clinical benefits of 40Hz sensory stimulation in AD patients. Here we ask whether neurophysiological responses to sensory gamma stimulation would predict clinical outcome in subjects with AD.     

The data presented here were from the Overture study (NCT03556280). In this study, participants in the treatment group used GammaSense Stimulation System (Cognito Therapeutics, Inc., Cambridge, MA), a medical device that delivers 40Hz auditory and visual stimulation, for daily, 1 hour treatment during the 6-month trial. Participants in the control group received sham stimulation. We identified participants who have baseline EEG recordings along with cognitive, functional and brain structural evaluation (n=16).  Changes in z-transformed clinical evaluations relative to baseline were examined as a function of baseline EEG coherence.  Singular value decomposition was used to represent the changes in clinical outcomes with a single unified measure and to determine the degree of correlation of this measure with baseline EEG coherence.

Dependence of the unified measure on the baseline EEG coherence differed significantly between the two groups (p<.04), where higher baseline sensory-evoked EEG coherence corresponded to better outcome in the treatment group participants.

Our results suggest that patients with higher EEG coherence in response to sensory stimulation respond better to 40Hz gamma sensory stimulation therapy. These findings raise the possibility that EEG response characteristics to sensory stimuli can be an important determinant for patient selection in clinical studies. Further work is needed to understand the neurophysiological mechanisms contributing to the clinical outcome of the therapy.