The safety and efficacy of gamma frequency auditory and visual stimulation in the treatment of alzheimer's disease: a systematic review and meta-analysis.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of controlled trials
PubMed 41381439 · doi:10.1038/s41398-025-03788-4
What was done
A systematic review and meta-analysis evaluated 40 Hz gamma-frequency auditory and visual stimulation (GFAVS) in adults aged 50 and older with Alzheimer's disease (AD) or mild cognitive impairment (MCI). Databases (PubMed, Cochrane Library, MEDLINE, Web of Science, Embase) were searched through November 2025 for controlled trials. Outcomes assessed were adverse events, cognitive function, activities of daily living, and structural brain changes.
What was found
Across 11 studies with 341 participants, GFAVS showed no significant increase in overall adverse events (RR = 0.99, P = 0.93; RD = -0.01, P = 0.93), but did increase the risk of tinnitus (RR = 6.46, P = 0.08; RD = 0.16, P = 0.01). GFAVS was associated with significant structural brain improvements (SMD = 1.74, P = 0.02; SMD = 3.05, P < 0.00001 in mixed AD and MCI populations). However, no significant improvements were found for cognitive function (SMD = 0.16, 95% CI [-0.36 to 0.68], P = 0.55) or activities of daily living (SMD = 0.53, 95% CI [-1.26 to 2.33], P = 0.56).
Why it matters
Despite evidence of structural brain alterations, current evidence does not demonstrate clinical or functional cognitive benefits from gamma-frequency sensory stimulation in AD or MCI.
Limits
The total sample size was small (341 participants across 11 studies), leading to wide confidence intervals. High heterogeneity was observed across studies, and optimal treatment parameters, duration, and long-term clinical effects remain uncharacterized.
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