Efficacy of probiotic supplementation in influencing cognitive function in Alzheimer's disease: A systematic review and meta‐analysis

Abstract Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and behavioral changes. Emerging evidence suggests that the gut microbiota influences central nervous system function. Probiotic interventions may offer a promising therapeutic approach by modulating the gut microbiota composition and potentially improving cognitive outcomes in AD patients. This meta‐analysis aimed to assess the effects of probiotic supplementation on cognitive function in AD patients by analyzing randomized controlled trials (RCTs). Following PRISMA 2020 guidelines and registered with PROSPERO (CRD42024508725), we conducted a comprehensive search across PubMed, Embase, Cochrane Library, and ClinicalTrials.gov through April 9th, 2024. Only double‐blind RCTs comparing probiotic supplementation to placebo in patients aged 65 or older with clinically diagnosed AD were included. Primary outcomes were cognitive function scores from validated tools like MMSE and TYM. Our stringent inclusion criteria identified four double‐blind RCTs with 251 participants aged 65 or older with clinically diagnosed AD. Statistical analysis using a random‐effects model revealed significant cognitive improvement in probiotic‐treated groups compared to placebo controls (Standardized Mean Difference [SMD] = 0.67; 95% CI [0.14, 1.19]; P < 0.05), though substantial heterogeneity was observed (I 2 = 79.16%). Subgroup analyses indicated that probiotic formulation type, dosage, and baseline AD severity may influence cognitive outcomes. While these findings suggest probiotics may offer cognitive benefits for AD patients, the high heterogeneity and limited study number necessitate additional well‐designed clinical trials to confirm these promising results and establish optimal treatment protocols for clinical implementation.