A randomized pilot trial of non-flickering 40 Hz light stimulation: EEG activity and cognitive outcomes in cognitively normal older adults.

BackgroundGamma-frequency (40 Hz) sensory stimulation is a promising non-pharmacological approach for modulating neural activity and cognitive function in aging and Alzheimer's disease. However, conventional flickering stimulation is often poorly tolerated, and evidence for non-flickering approaches remains limited.ObjectiveTo evaluate the neurophysiological and cognitive effects of 4-week (28-session) non-flickering 40 Hz light stimulation in cognitively normal older adults.MethodsIn this randomized, double-blind, active-controlled pilot trial, 33 cognitively normal older adults were assigned to receive either non-flickering 40 Hz light stimulation (n = 17) or a 70 Hz active-controlled condition (n = 16) over four weeks. Per-protocol analyses were conducted in 29 participants who completed the intervention. Resting-state electroencephalography (EEG) was acquired at baseline, immediately after the first intervention session, and after completion of the 4-week intervention. Neuropsychological assessments were performed at baseline and after the intervention. Prespecified primary outcomes were resting-state gamma-band power spectral density (PSD) and functional connectivity (FC).ResultsNo significant between-group differences were observed in resting-state gamma-band PSD or FC following either one-session or 28-session intervention. Unadjusted secondary analyses suggested potential improvements in selected episodic memory measures in the 40 Hz group. Exploratory analyses further identified a positive association between improvements in visuospatial memory and increases in occipital-temporal FC. Both interventions were well tolerated.ConclusionsA 28-session non-flickering 40 Hz light stimulation was well tolerated and may improve selected episodic memory measures in cognitively normal older adults. Although no measurable group-level EEG effects were observed, the exploratory cognitive findings warrant further investigation in larger randomized trials.ClinicalTrial.gov (ID: NCT06715995) https://clinicaltrials.gov/expert-search?term=NCT06715995.