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Meta-Analysis
. 2025 Dec 11;15(1):523.
doi: 10.1038/s41398-025-03788-4.

The safety and efficacy of gamma frequency auditory and visual stimulation in the treatment of alzheimer's disease: a systematic review and meta-analysis

Shaojia Ang #  1   2   3   4 , Xinyue Zhang #  1   2 , Jialong Hong  1   5 , Kaiyao Xue  1   2 , Jianhong Li  1 , Xinzhe Du  1   2 , Yao Gao  1   2 , Xiao Wang  1   2 , Xinrong Li  1 , Bo Chen  6 , Yang Li  7 , Jihui Zhang  8 , Sha Liu  9   10
Affiliations
Meta-Analysis

The safety and efficacy of gamma frequency auditory and visual stimulation in the treatment of alzheimer's disease: a systematic review and meta-analysis

Shaojia Ang et al. Transl Psychiatry. .

Abstract

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated with cognitive decline and significant global health burden. Current treatments offer limited benefits, highlighting the need for novel therapies. Gamma-frequency auditory and visual stimulation (GFAVS), utilizing 40 Hz neuromodulation, has gained attention as a non-invasive treatment for cognitive deficits and underlying pathophysiology in AD.

Objective: This systematic review and meta-analysis aimed to assess the safety and efficacy of GFAVS in treating Alzheimer's disease (AD) and mild cognitive impairment (MCI).

Methods: A comprehensive literature search across multiple databases (PubMed, Cochrane Library, MEDLINE, Web of Science, and Embase) was performed up to November 2025. Controlled trials involving adults (≥50 years) with AD or MCI, using GFAVS, were included. Meta-analyses assessed adverse events, cognitive function, and brain changes.

Results: Eleven studies (341 participants) were included. GFAVS was safe, with no significant increase in overall adverse events (RR = 0.99, P = 0.93; RD = -0.01, P = 0.93). However, GFAVS significantly increased the risk of tinnitus (RR = 6.46, P = 0.08; RD = 0.16, P = 0.01). GFAVS significantly improved structural brain changes (SMD = 1.74, P = 0.02), especially in mixed AD and MCI populations (SMD = 3.05, P < 0.00001). Nevertheless, no significant improvements were observed in 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), despite the observed structural brain changes. High heterogeneity was observed.

Conclusion: GFAVS appears to be well tolerated and may induce structural brain alterations in individuals with Alzheimer's disease or mild cognitive impairment; however, its impact on cognition or daily functioning remains to be established. Large-scale, rigorously designed trials are required to clarify optimal protocols and address the observed heterogeneity.

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Conflict of interest statement

Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Flow chart of literature search.
Fig. 2
Fig. 2
Quality assessment of included studies.
Fig. 3
Fig. 3
A Forest plot of risk ratio (RR) for the incidence of adverse events. B Forest plot of risk ratio (RR) for the incidence of headache. C Forest plot of risk ratio (RR) for the incidence of tinnitus. D Forest plot of risk ratio (RR) for the incidence of dizziness. E Forest plot of risk ratio (RR) for the incidence of anxiety. F Forest plot of risk ratio (RR) for the incidence of agitation. G Forest plot of risk ratio (RR) for the incidence of disorientation.
Fig. 4
Fig. 4
Forest plot of structural changes in the brain.
Fig. 5
Fig. 5
Forest plot of cognitive function.
Fig. 6
Fig. 6
Forest plot of ability of daily living activities.
Fig. 7
Fig. 7
Forest plot of the subgroup analysis for structural changes in the brain.
Fig. 8
Fig. 8
Sensitivity analysis of structural changes in the brain.
Fig. 9
Fig. 9
Sensitivity analysis of ability of daily living activities.
See this image and copyright information in PMC

References

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