The Effects and Safety of Gamma Rhythm Stimulation on Cognitive Function in Alzheimer’s Disease: A Systematic Review and Meta-Analysis

Objective Researchers have focused on gamma rhythm stimulation, particularly at 40 Hz, to enhance endogenous gamma oscillations and improve cognitive function and outcomes in Alzheimer’s disease (AD). However, some studies disputed these findings. This review aimed to systematically analyze recent randomized controlled trials on the effects of gamma stimulation on cognitive function in AD and to perform a meta-analysis to assess the efficacy, safety, and differences between brain and sensory stimulation. Methods A systematic search was conducted in PubMed, Web of Science, Ovid-Embase, and Ovid-MEDLINE from their inception to April 2024. A meta-analysis was performed to evaluate adverse events and cognitive function assessed using AD Assessment Scale-Cognitive Subscale (ADAS-cog), Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Face-Name Association Test (FNAT). Subgroup analyses were performed to explore the heterogeneity between the brain and sensory stimulation. Results Eight studies involving 291 participants were included. Meta-analysis demonstrated a large benefit in cognitive function: FNAT (standardized mean difference [SMD] = 3.76; 95% confidence interval [CI] = 2.52-4.99; I 2 = 65%), MMSE (SMD = 3.09; 95% CI = 2.37-3.82; I 2 = 0%), ADAS-cog (SMD = −4.16; 95% CI = −6.60 to −2.62; I 2 = 0%), and MoCA (SMD = 2.17; 95% CI = −0.54 to 4.88; I 2 = 0%). There were no significant differences in adverse events between the intervention and sham groups ( P = .06), suggesting the safety of gamma stimulation. Conclusion This review highlights the safety and benefits of gamma stimulation for cognitive improvement in patients with AD, with sensory stimulation proving safe even in individuals with epilepsy.