Efficacy of auditory gamma stimulation for cognitive decline: a systematic review of individual and group differences across cognitively impaired and healthy populations.

Auditory gamma stimulation is a promising non-invasive neuromodulation technique for cognitive decline, with preclinical studies demonstrating therapeutic effects in Alzheimer's disease models. However, translating these findings into human trials has produced variable outcomes, suggesting a need to examine factors influencing efficacy. In a systematic review of 62 studies on healthy and cognitively impaired populations, we identified 16 characteristics that may affect the response to stimulation. Outcomes reported included improved cognition, slower progression of brain atrophy, and changes in functional connectivity. Optimal stimulation frequency varied across individuals, indicating that personalised approaches may be valuable. Importantly, animal-model findings regarding amyloid clearance and reduced neuroinflammation were not consistently replicated in human studies, nor did neurophysiological responses reliably predict cognitive or biological effects. Significant methodological diversity was evident, with 32 neurophysiological measures employed, highlighting a need for standardisation. Future research should prioritise consensus on outcome measurement and explore individualised intervention strategies to better assess therapeutic potential.