Targeting brain rhythms to support cognition in aging: a systematic review and meta-analysis of tACS across healthy aging, mild cognitive impairment, and Alzheimer’s disease
摘要
Cognitive decline is a major challenge in aging. Transcranial alternating current stimulation (tACS) modulates neural oscillations, potentially aiding cognition. Due to variation in late-life tACS studies, we conducted the first meta-analysis in older adults (≥ 60 years) to estimate pooled cognitive effects and determine if protocol parameters explain outcome variability. We searched Medline/PubMed, Embase, Cochrane Library, and ClinicalTrials.gov (up to September 17, 2025) for studies examining tACS effects on cognition in adults age ≥ 60 years, including healthy aging, mild cognitive impairment (MCI), and Alzheimer’s disease (AD). Risk of bias was assessed using RoB 2 and ROBINS-I. Random-effects meta-analyses using Hedges’ g were performed, with sensitivity analyses to handle outliers and heterogeneity. Twenty-two studies (n = 826 participants) were included. The primary meta-analysis revealed a significant moderate effect of tACS on cognition (g = 0.70, 95% CI 0.38–1.02), though with high heterogeneity (I2 = 88.5%). Excluding one influential outlier yielded a more conservative and stable estimate (g = 0.55, 95% CI 0.39–0.70, I2 = 47.1%). Subgroup analyses showed homogenous effects in MCI (g = 0.59, I2 = 0%). Memory was the most responsive domain. Meta-regressions did not identify significant associations between outcomes and specific stimulation parameters. tACS was associated with improvements in cognitive outcomes in older adults, with more consistent evidence observed for memory in individuals with MCI. However, findings in healthy older adults and AD were more variable and should be interpreted in light of substantial methodological heterogeneity. Overall, the pooled estimate reflects an average across diverse populations and intervention protocols rather than a single, clinically uniform effect. Future research should prioritize standardized, dose-response protocols to support clinical translation. PROSPERO CRD42025629824.