Effectiveness of noninvasive brain stimulation techniques on cognitive function in individuals with Alzheimer’s disease and MCI: a systematic review and meta-analysis

Abstract

Background Noninvasive brain stimulation (NIBS) may alleviate cognitive impairments in individuals with Alzheimer’s disease (AD). However, clinical findings remain inconsistent, highlighting the need for a systematic review and meta-analysis to clarify the efficacy of NIBS. Objective To compare the effects of NIBS and sham stimulation on global cognition in individuals with AD. Methods Randomized controlled trials were identified from PubMed, Web of Science, Scopus, and the Cochrane Central Register of Controlled Trials by using relevant search terms. Cognitive outcomes were assessed using objective scales, and pooled standardized mean differences with 95% confidence intervals (CIs) were calculated using a random-effects model. Results NIBS was associated with significant improvements in global cognition in individuals with AD, as measured using the Mini-Mental State Examination (MMSE; standardized mean difference = 0.58, 95% CI = 0.32 to 0.84, p < 0.001) and Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog; standardized mean difference = −0.40, 95% CI = −0.68 to −0.13, p = 0.004). The subgroup analysis revealed that treatment is efficacious when patients are stable medication users for 3 months or less (MMSE scores), intervention is delivered for 6 weeks, and NIBS is administered singularly. Longer duration of pharmacological treatment was associated with reduced NIBS efficacy on MMSE scores in both the meta-regression and subgroup analyses. Cognitive gains based on MMSE outcomes were maintained at 4 and 8 weeks after treatment. Conclusion This meta-analysis provides evidence for the effects of NIBS on common cognitive outcomes in AD and explores potential moderators related to sample and intervention characteristics. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420251065634.