The Dose and Duration-dependent Association between Melatonin Treatment
and Overall Cognition in Alzheimer’s Dementia: A Network Meta-
Analysis of Randomized Placebo-Controlled Trials

Ping-Tao      Tseng; Bing-Yan      Zeng; Yen-Wen      Chen; Chun-Pai      Yang; Kuan-Pin      Su; Tien-Yu      Chen; Yi-Cheng      Wu; Yu-Kang      Tu; Pao-Yen      Lin; Andre   F.   Carvalho; Brendon      Stubbs; Yutaka   J.   Matsuoka; Dian-Jeng      Li; Chih-Sung      Liang; Chih-Wei      Hsu; Cheuk-Kwan      Sun; Yu-Shian      Cheng; Pin-Yang      Yeh; Yow-Ling      Shiue
doi:10.2174/1570159X20666220420122322
Abstract

Background: While Alzheimer’s dementia (AD) has a prevalence as high as 3-32% and is associated with cognitive dysfunction and the risk of institutionalization, no efficacious and acceptable treatments can modify the course of cognitive decline in AD. Potential benefits of exogenous melatonin for cognition have been divergent across trials.
Objective: The current network meta-analysis (NMA) was conducted under the frequentist model to evaluate the potential beneficial effects of exogenous melatonin supplementation on overall cognitive function in participants with AD in comparison to other FDA-approved medications (donepezil, galantamine, rivastigmine, memantine, and Namzaric).
Methods: The primary outcome was the changes in the cognitive function [measured by mini-mental state examination (MMSE)] after treatment in patients with Alzheimer’s dementia. The secondary outcomes were changes in the quality of life, behavioral disturbance, and acceptability (i.e., drop-out due to any reason and rate of any adverse event reported).
Results: The current NMA of 50 randomized placebo-controlled trials (RCTs) revealed the medium-term lowdose melatonin to be associated with the highest post-treatment MMSE (mean difference = 1.48 in MMSE score, 95% confidence intervals [95% CIs] = 0.51 to 2.46) and quality of life (standardized mean difference = -0.64, 95% CIs = -1.13 to -0.15) among all of the investigated medications in the participants with AD. Finally, all of the investigated exogenous melatonin supplements were associated with similar acceptability as was the placebo.
Conclusion: The current NMA provides evidence for the potential benefits of exogenous melatonin supplementation, especially medium-term low-dose melatonin, in participants with AD.
Keywords: Alzheimer’s dementia, quality of life, cognition, network meta-analysis, dementia, melatonin, circadian rhythm, psychiatry.
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Graphical Abstract

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DOI https://dx.doi.org/10.2174/1570159X20666220420122322	Print ISSN 1570-159X
Publisher Name Bentham Science Publisher	Online ISSN 1875-6190
Current Neuropharmacology

The Dose and Duration-dependent Association between Melatonin Treatment and Overall Cognition in Alzheimer’s Dementia: A Network Meta- Analysis of Randomized Placebo-Controlled Trials

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