Comparative efficacy of neuromodulation techniques for Alzheimer's disease: a systematic review and network meta-analysis of randomized controlled trials.

BACKGROUND: Neuromodulation techniques (NMTs) have shown potential therapeutic value in Alzheimer's disease (AD), but the comparative efficacy of different modalities remains unclear. This study aimed to systematically compare and rank available NMTs to identify their relative benefits across cognitive, functional, and neuropsychiatric outcomes. OBJECTIVE: To evaluate and rank the efficacy of NMTs in improving cognitive function, activities of daily living (ADLs), and neuropsychiatric symptoms in AD patients, thereby providing evidence-based guidance for clinical intervention strategies. METHODS: English-language literature was systematically searched in PubMed, Web of Science, Cochrane Library, and EMBASE from database inception to February 2026. Inclusion criteria were randomized controlled trials (RCTs) of AD patients aged ≥18 years. Interventions included repetitive transcranial magnetic stimulation (rTMS), transcranial alternating current stimulation (tACS), transcranial direct current stimulation (tDCS), photobiomodulation (PBM), transcutaneous electrical stimulation (TES), transcranial ultrasound stimulation (TUS), transcranial pulse stimulation (TPS), deep brain stimulation (DBS), and sham stimulation (Sham). Outcome measures included Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Alzheimer' s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), Alzheimer' s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL), Boston Naming Test (BNT), Neuropsychiatric Inventory (NPI), and Geriatric Depression Scale (GDS). Data extraction and risk-of-bias assessment followed Cochrane guidelines. Network meta-analysis (NMA) was conducted in Stata 17.0, with effect sizes ranked by the surface under the cumulative ranking curve (SUCRA). RESULTS: A total of 36 RCTs involving 1,445 patients were included in the analysis. Compared with Sham, TPS significantly improved MMSE (MD = 3.92, 95% CI: 1.57 to 6.35; SUCRA = 97.50%), MoCA (MD = 4.99, 95% CI: 2.26 to 7.72; SUCRA = 69.25%), and BNT scores (MD = 4.02, 95% CI: 1.81 to 6.23; SUCRA = 81.8%). rTMS also showed favorable effects on ADAS-Cog scores (MD = -11.10, 95% CI: -14.51 to -7.71; SUCRA = 91.00%). Regarding activities of daily living, TES ranked highest on the ADCS-ADL scale (SUCRA = 71.00%). In terms of neuropsychiatric symptoms, TPS achieved the highest ranking for improving NPI scores (SUCRA = 92.3%), whereas tACS showed the best performance on GDS scores (SUCRA = 69.5%). CONCLUSION: Neuromodulation interventions demonstrated domain-specific benefits in AD, with no single approach showing universal superiority. TPS demonstrated the greatest potential for improving global cognitive outcomes, while rTMS showed advantages in ADAS-Cog performance. Nevertheless, limited sample sizes, heterogeneous stimulation protocols, and insufficient long-term evidence restrict the generalizability of current findings. Future multicenter RCTs with standardized protocols and prolonged follow-up are needed to confirm these results and guide clinical implementation. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD420261364193.