Clinical efficacy of non-pharmacological interventions on cognitive improvement in patients with mild to moderate Alzheimer's disease: A systematic review and Bayesian network meta-analysis
Abstract
Background Non-pharmacological interventions are increasingly used as complementary strategies for Alzheimer's disease (AD), yet their comparative effects on cognitive outcomes remain insufficiently defined. Objective To compare and rank the cognitive effects of different non-pharmacological interventions in patients with mild-to-moderate AD. Methods Randomized controlled trials of non-pharmacological interventions for mild-to-moderate AD were searched in MEDLINE, PubMed, Embase, Web of Science, and the Cochrane Library from inception to May 2026. Eligible studies reported cognitive outcomes, including the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), or Alzheimer's Disease Assessment Scale–Cognitive Subscale (ADAS-Cog). Risk of bias was assessed using the Cochrane tool, and certainty of evidence was evaluated with GRADEpro. Bayesian network meta-analysis was conducted in R using gemtc. The surface under the cumulative ranking curve was used to estimate intervention rankings. Results Fifty randomized controlled trials involving 2856 participants and 11 categories of interventions were included. Among participants with available baseline age data, the weighted mean age was approximately 75 years; among those with available sex information, 1410 participants were female (54.0%). Dual-task training ranked first for MMSE (SUCRA = 88.84%) and MoCA (SUCRA = 90.67%). Transcranial direct current stimulation (tDCS) also showed favorable rankings for MMSE (SUCRA = 85.69%) and MoCA (SUCRA = 75.63%). For ADAS-Cog, repetitive transcranial magnetic stimulation (rTMS) ranked highest (SUCRA = 85.22%) and was the only intervention showing significant improvement compared with usual care. Conclusions Dual-task training and tDCS showed relatively consistent advantages on global cognitive screening outcomes in mild-to-moderate AD. rTMS showed the clearest benefit for ADAS-Cog, but this finding requires cautious interpretation.