Network meta-analysis of different traditional Chinese medicine therapies as adjuvant treatments for Alzheimer's disease

BACKGROUND AND PURPOSE: Alzheimer's disease (AD) is a major global health challenge. While various traditional Chinese medicine (TCM) therapies are widely used as adjuncts to conventional Western medicine, their relative efficacy and safety remain unclear due to the lack of direct comparisons. This network meta-analysis aimed to compare and rank different TCM adjuvant therapies for AD, to inform evidence-based clinical decision-making. METHODS: Randomized controlled trials (RCTs) evaluating TCM therapies as adjuncts to conventional Western medicine (CWM) for AD were searched in eight databases, including the China National Knowledge Infrastructure (CNKI), Wanfang Data, PubMed, and Web of Science, from inception to January 1, 2025. Two independent reviewers performed study selection, data extraction, and risk-of-bias assessment using the Cochrane risk-of-bias tool for randomized trials (RoB 2.0). Network meta-analysis was conducted using RevMan 5.4 and Stata 16.0. RESULTS: Thirty-one RCTs involving 3221 patients with AD were included, comprising seven interventions: CWM plus Chinese herbal medicine (CHM), CWM plus acupuncture (Acup), CWM plus Chinese patent medicine (CPM), CWM plus Acup and acupoint application (AA), CWM plus Acup and CPM, CWM plus Acup and CHM, and CWM alone. For clinical total effective rate, CWM + Acup + AA ranked first [odds ratio (OR) = 10.71; 95% confidence interval (CI), 3.44-33.33; surface under the cumulative ranking curve (SUCRA), 94.5%]. For Mini-Mental State Examination (MMSE) score, CWM + CHM + Acup ranked first [standardized mean difference (SMD) = 3.01; 95% CI, 1.65-4.37; SUCRA, 97.2%]. For Activities of Daily Living (ADL) score, CWM + Acup + AA ranked first (SMD = 4.10; 95% CI, 1.18-7.02; SUCRA, 99.2%). For Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) score, CWM + CHM + Acup ranked first (SMD = 2.43; 95% CI, 0.43-4.43; SUCRA, 89.3%). CWM + CPM ranked first for interleukin (IL)-1β (SMD = 1.73; 95% CI, 0.82-2.65; SUCRA, 83.8%), IL-6 (SMD = 3.47; 95% CI, 2.29-4.65; SUCRA, 96.3%), and tumor necrosis factor-alpha (TNF-α) (SMD = 3.71; 95% CI, 2.86-4.56; SUCRA, 100%). For serum superoxide dismutase (SOD), CWM + (CHM + Acup) ranked first (SMD = 2.78; 95% CI, 0.87-4.69; SUCRA, 94.1%). CONCLUSION: Available evidence suggests that CPM added to CWM may offer advantages for inflammatory biomarkers, while acupuncture-based combinations may be advantageous for selected clinical and functional outcomes. Treatment choice should therefore be guided by the therapeutic target and the certainty of the supporting evidence. Because several comparisons were supported by few studies and overall certainty was low to very low for major outcomes, these findings require confirmation in rigorously designed trials.