Abstract
INTRODUCTION: This systematic review and meta-analysis aimed to compare the efficacy of extended supplementation (≥6 weeks) with natural compounds or extracts in improving cognitive function in patients with mild cognitive impairment (MCI) or Alzheimer's disease (AD). METHODS: A comprehensive literature search was conducted across Cochrane, PubMed, PsycARTICLES, Scopus, and Web of Science databases from inception to April 10, 2024. Eligible studies were randomized controlled trials evaluating cognitive outcomes in patients with MCI or AD using the Mini-Mental State Examination (MMSE) and the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog). RESULTS: From an initial pool of 6,687 articles, 45 were deemed relevant for qualitative analysis. Of these, 37 studies demonstrated improvements or positive trends in cognitive outcomes with natural compound or extract supplementation. A total of 35 studies met the criteria for meta-analysis. The meta-analysis, involving 4,974 participants, revealed significant improvements in ADAS-Cog scores (pooled standardized mean difference = -2.88, 95% confidence interval [CI]: -4.26 to -1.50; t(24) = -4.31, p < 0.01) following supplementation. Additionally, a suggestive trend toward improvement in MMSE scores was observed in a subgroup analysis of 1,717 participants (pooled standardized mean difference = 0.76, 95% CI: 0.06 to 1.46, t(18) = 2.27, p = 0.04). CONCLUSION: These findings support the potential cognitive benefits of extended (≥6 weeks) supplementation with natural compounds or extracts in individuals with MCI or AD. Further research is warranted to confirm these results and elucidate the underlying mechanisms. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/.