ABSTRACT: Background: Mild cognitive impairment (MCI) is the early phase of Alzheimer's disease (AD). The aim of early intervention for MCI is to decrease the rate of conversion from MCI to AD. However, the efficacy of multiple interventions in MCI, and the optimal methods of delivery, remain controversial. We aimed to compare and rank the treatment methods for MCI in AD, in order to find an optimal intervention for MCI and a way to prevent or delay the occurrence of AD. Methods: Pair-wise and network meta-analysis were conducted to integrate the treatment effectiveness through direct and indirect evidence. Four English databases and three Chinese databases were searched for international registers of eligible published, single or double blind, randomized controlled trials up to September 31st 2019. We included nine comparative interventions: pharmacological therapies which incorporated cholinesterase inhibitors (ChEI), ginkgo, nimodipine, and Chinese medicine; non-pharmacological therapies comprising of acupuncture, music therapy, exercise therapy, and nutrition therapy; and a placebo group. The primary outcome was the Mini-Mental State Examination (MMSE) score. The secondary outcome was the AD Assessment Scale-cognitive subscale (ADAS-cog). Results: Twenty-eight trials were eligible, including 6,863 participants. In the direct meta-analysis, as for the Mini-Mental State Examination scale, the ChEIs (MD: -0.38; 95% CI: -0.74, -0.01), Chinese medicine (MD: -0.31; 95% CI: -0.75, 0.13), exercise therapy (MD: -0.50; 95% CI: -0.65, -0.35), music therapy (MD: -1.71; 95% CI: -4.49, 1.07), were statistically more efficient than placebo. For AD Assessment Scalecognitive subscale outcome, ChEIs (MD: 1.20; 95% CI: 0.73, 1.68), Acupuncture (MD: 1.36; 95% CI: 1.28, 1.44), Chinese medicine (MD: 0.61; 95% CI: 0.49, 0.73) and exercise (MD: 0.61; 95% CI: 0.49, 0.73) were better than placebo. In the network meta-analysis, the MMSE outcome ranked music therapy (59%) as the best and Acupuncture (26%) as second. Nutrition and Ginkgo treatment had the lowest rank among all interventions. For ADAS-cog outcome, acupuncture (52) ranked the best. Conclusion: Among the nine treatments studied, music therapy appears to be the best treatment for MCI, followed by acupuncture. Our study provides new insights into potential clinical treatments for MCI due to AD, and may aid the development of guidelines for MCI in AD.
