Preliminary study of sex-based neural responses and cognitive benefits of a 40 Hz rhythmic light intervention in mild cognitive impairment

Background: Sex differences in the brain's structure, function, and response to interventions are increasingly recognized as critical factors in neurodegenerative diseases like mild cognitive impairment (MCI) and Alzheimer's disease. Objective: This study investigated sex differences in brain activity among participants classified as having MCI (based on Montreal Cognitive Assessment scores) during exposure to a 40 Hz rhythmic light (RL) intervention versus a control RL condition. Methods: Twenty-four participants in the MCI group (mean age = 74.5 years, SD = 9.06; 15 women, 9 men) and 16 age-matched healthy controls (mean age = 70 years, SD = 8.97; 9 women, 7 men) were exposed to both light conditions and underwent electroencephalography recordings, cognitive performance testing (2-back task), and a subjective assessment of sleepiness (Karolinska Sleepiness Scale). Results: 40 Hz RL increased gamma power significantly, indicating its potential to enhance brain function, especially in the MCI group. Men showed greater neural response and better cognitive performance under the 40 Hz RL while women (particularly in the MCI group) responded more strongly to the control. The sleepiness results were not significant. Conclusions: There is compelling evidence that 40 Hz RL has sex-dependent effects on gamma oscillations and cognitive performance, particularly in individuals with MCI. Men may benefit more directly from gamma-enhancing interventions, whereas women may require alternative approaches that account for their unique neural responses to light. Further research with larger, more diverse populations is needed to confirm these findings and explore the potential for personalized therapeutic strategies based on sex and cognitive status.