The purpose of this review was to systematically review all the latest clinical randomized controlled trials of gamma rhythm stimulation on cognitive function in people with AD and to apply meta-analysis to evaluate their effects, safety, and the differences between the two types of stimulation. The secondary objective is to explore the possible therapeutic mechanisms.
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 the ADAS-cog, MMSE, MoCA, and FNAT. Subgroup analyses were performed to explore the heterogeneities between brain stimulation and sensory stimulation.
Eight studies were included, involving 291 participants and two main types of stimulation: brain stimulation (TMS, tACS, tDCS, TMS-tDCS) and sensory stimulation (visual stimulation, auditory stimulation, visual-auditory stimulation). The meta-analysis results for FNAT (SMD 3.76; 95% CI 2.52 to 4.99; I² = 65%), MMSE (SMD 3.09; 95% CI 2.37 to 3.82; I² = 0%), ADAS-cog (SMD -4.16; 95% CI -6.60 to -2.62; I² = 0%), and MoCA (SMD 2.17; 95% CI -0.54 to 4.88; I² = 0%) indicated a large benefit from gamma stimulation on cognitive function. In addition, there was no significant difference (FNAT p=0.32; MMSE p=0.06; ADAS-cog p=0.93; MoCA p=0.7) between the results of brain stimulation and sensory stimulation. Furthermore, the meta-analysis of adverse events showed no significant difference (P=0.06) between the intervention and sham stimulation groups, favoring the safety of gamma stimulation.
The present review highlights that gamma stimulation, including brain stimulation and sensory stimulation, can safely provide a large benefit for cognitive improvement in people with AD. Notably, sensory stimulation is safe enough to be used even in patients with epilepsy.
This review demonstrates that gamma stimulation appears to be ready for clinical application in terms of sufficient efficacy and safety, providing clinicians with evidence for the selection of new treatments, and encouraging more researchers to study specific therapeutic parameters and mechanisms in the future.
rhythmic stimulation
gamma entrainment
