Noninvasive Gamma Sensory Stimulation May Reduce White Matter and Myelin Loss in Alzheimer's Disease

Background: Patients with Alzheimer's disease (AD) demonstrate progressive white matter atrophy and myelin loss. Restoring myelin content or preventing demyelination has been suggested as a therapeutic approach for AD. Objective: Herein, we investigate the effects of non-invasive, combined visual and auditory gamma-sensory stimulation on white matter atrophy and myelin content loss in patients with AD. Methods: In this study, we used the magnetic resonance imaging (MRI) data from the OVERTURE study (NCT03556280), a randomized, controlled, clinical trial in which active treatment participants received daily, non-invasive, combined visual and auditory, 40Hz stimulation for six months. A subset of OVERTURE participants who meet the inclusion criteria for detailed white matter (N = 38) and myelin content (N = 36) assessments are included in the analysis. White matter volume assessments were performed using T1-weighted MRI, and myelin content assessments were performed using T1-weighted/T2-weighted MRI. Treatment effects on white matter atrophy and myelin content loss were assessed. Results: Combined visual and auditory gamma-sensory stimulation treatment is associated with reduced total and regional white matter atrophy and myelin content loss in active treatment participants compared to sham treatment participants. Across white matter structures evaluated, the most significant changes were observed in the entorhinal region. Conclusions: The study results suggest that combined visual and auditory gamma-sensory stimulation may modulate neuronal network function in AD in part by reducing white matter atrophy and myelin content loss. Furthermore, the entorhinal region MRI outcomes may have significant implications for early disease intervention, considering the crucial afferent connections to the hippocampus and entorhinal cortex.