Effects of dietary supplements on cognitive outcomes and physiological biomarkers in mild cognitive impairment: a systematic review and network meta-analysis.

Abstract

Mild cognitive impairment (MCI) represents a transitional stage between normal aging and dementia, affecting a significant proportion of the elderly population. Non-pharmacological nutritional supplements, such as vitamins, omega-3 fatty acids, probiotics, and herbal extracts, have been proposed as potential interventions to mitigate cognitive decline and improve physiological biomarkers. However, evidence on their efficacy remains inconsistent. This systematic review and network meta-analysis (NMA) aimed to evaluate the effectiveness of various non-pharmacological nutritional supplements on cognitive function and key physiological indicators (e.g., BDNF, Aβ42, Aβ40) in elderly individuals with MCI. This systematic review followed PRISMA-NMA guideline and was registered in PROSPERO (CRD420251079079). We searched PubMed, Embase, Cochrane Library, Web of Science, and CNKI databases from inception to June 2025 for randomized controlled trials (RCTs) comparing dietary supplements to placebo or no intervention. Data extraction included cognitive scores (e.g., MMSE, MoCA, FSIQ) and physiological markers. Risk of bias was assessed using the Cochrane Risk of Bias Tool. Pairwise meta-analyses and NMA were conducted using random-effects models, with standardized mean differences (SMD) for continuous outcomes. Heterogeneity was assessed via I 2 statistics, and sensitivity analyses were performed to test robustness. Thirteen trials involving 2,451 participants were included. PUFA supplements showed the greatest cognitive benefit ( SMD 0.91; 95% CI 0.21-1.61) and ranked first according to SUCRA values. Supplementation significantly reduced Aβ42 levels, while effects on BDNF and Aβ40 were non-significant. Heterogeneity was substantial ( I 2 = 96%), and sensitivity analyses demonstrated attenuated effect sizes after removing studies at high risk of bias. Dietary supplements may offer potential cognitive benefits in MCI, but evidence is limited by study quality and heterogeneity. High-quality RCTs are needed to confirm these findings. Identifier CRD420251079079.