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^{1

2

3

4}, Bing-Yan Zeng⁵, Yen-Wen Chen¹, Chun-Pai Yang^{6

7}, Kuan-Pin Su^{8

9

10

11}, Tien-Yu Chen^{12

13}, Yi-Cheng Wu¹⁴, Yu-Kang Tu^{15

16}, Pao-Yen Lin^{17

18}, Andre F Carvalho¹⁹, Brendon Stubbs^{11

20

21}, Yutaka J Matsuoka^{8

22}, Dian-Jeng Li²³, Chih-Sung Liang^{24

25}, Chih-Wei Hsu¹⁷, Cheuk-Kwan Sun²⁶, Yu-Shian Cheng^{2

27}, Pin-Yang Yeh^{3

4}, Yow-Ling Shiue²⁸

Affiliations

¹ Prospect Clinic for Otorhinolaryngology & Neurology, Kaohsiung, Taiwan.
² Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan.
³ Department of Psychology, College of Medical and Health Science, Asia University, Taichung, Taiwan.
⁴ Clinical Psychology Center, Asia University Hospital, Taichung, Taiwan.
⁵ Department of Internal Medicine, E-DA Dachang Hospital, Kaohsiung, Taiwan.
⁶ Department of Neurology, Kuang Tien General Hospital, Taichung, Taiwan.
⁷ Department of Nutrition, Huangkuang University, Taichung, Taiwan.
⁸ Department of Psychiatry & Mind-Body Interface Laboratory (MBI-Lab), China Medical University Hospital, Taichung, Taiwan.
⁹ College of Medicine, China Medical University, Taichung, Taiwan.
¹⁰ An-Nan Hospital, China Medical University, Tainan, Taiwan.
¹¹ Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
¹² Department of Psychiatry, Tri-Service General Hospital; School of Medicine, National Defense Medical Center, Taipei, Taiwan.
¹³ Institute of Brain Science, National Yang Ming Chiao Tung University, Taipei 112, Taiwan.
¹⁴ Department of Sports Medicine, Landseed International Hospital, Taoyuan, Taiwan.
¹⁵ Institute of Epidemiology & Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
¹⁶ Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan.
¹⁷ Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
¹⁸ Institute for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
¹⁹ Innovation in Mental and Physical Health and Clinical Treatment (IMPACT) Strategic Research Centre, School of Medicine, Barwon Health, Deakin University, Geelong, VIC, Australia.
²⁰ Physiotherapy Department, South London and Maudsley NHS Foundation Trust, London, UK.
²¹ Faculty of Health, Social Care Medicine and Education, Anglia Ruskin University, Chelmsford, UK.
²² Former Division Chief of Health Care Research, National Cancer Center, Japan.
²³ Department of Addiction Science, Kaohsiung Municipal Kai-Syuan Psychiatric Hospital, Kaohsiung City, Taiwan.
²⁴ Department of Psychiatry, Beitou Branch, Tri-Service General Hospital; School of Medicine, National Defense Medical Center, Taipei, Taiwan.
²⁵ Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.
²⁶ Department of Emergency Medicine, E-Da Hospital, I-Shou University School of Medicine for International Students, Taiwan.
²⁷ Department of Psychiatry, Tsyr-Huey Mental Hospital, Kaohsiung Jen-Ai's Home, Taiwan.
²⁸ Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.

PMID: 35450525
PMCID: PMC9886806
DOI: 10.2174/1570159X20666220420122322

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 et al. Curr Neuropharmacol. 2022.

. 2022;20(10):1816-1833.

doi: 10.2174/1570159X20666220420122322.

Authors

Affiliations

¹ Prospect Clinic for Otorhinolaryngology & Neurology, Kaohsiung, Taiwan.
² Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan.
³ Department of Psychology, College of Medical and Health Science, Asia University, Taichung, Taiwan.
⁴ Clinical Psychology Center, Asia University Hospital, Taichung, Taiwan.
⁵ Department of Internal Medicine, E-DA Dachang Hospital, Kaohsiung, Taiwan.
⁶ Department of Neurology, Kuang Tien General Hospital, Taichung, Taiwan.
⁷ Department of Nutrition, Huangkuang University, Taichung, Taiwan.
⁸ Department of Psychiatry & Mind-Body Interface Laboratory (MBI-Lab), China Medical University Hospital, Taichung, Taiwan.
⁹ College of Medicine, China Medical University, Taichung, Taiwan.
¹⁰ An-Nan Hospital, China Medical University, Tainan, Taiwan.
¹¹ Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
¹² Department of Psychiatry, Tri-Service General Hospital; School of Medicine, National Defense Medical Center, Taipei, Taiwan.
¹³ Institute of Brain Science, National Yang Ming Chiao Tung University, Taipei 112, Taiwan.
¹⁴ Department of Sports Medicine, Landseed International Hospital, Taoyuan, Taiwan.
¹⁵ Institute of Epidemiology & Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
¹⁶ Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan.
¹⁷ Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
¹⁸ Institute for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
¹⁹ Innovation in Mental and Physical Health and Clinical Treatment (IMPACT) Strategic Research Centre, School of Medicine, Barwon Health, Deakin University, Geelong, VIC, Australia.
²⁰ Physiotherapy Department, South London and Maudsley NHS Foundation Trust, London, UK.
²¹ Faculty of Health, Social Care Medicine and Education, Anglia Ruskin University, Chelmsford, UK.
²² Former Division Chief of Health Care Research, National Cancer Center, Japan.
²³ Department of Addiction Science, Kaohsiung Municipal Kai-Syuan Psychiatric Hospital, Kaohsiung City, Taiwan.
²⁴ Department of Psychiatry, Beitou Branch, Tri-Service General Hospital; School of Medicine, National Defense Medical Center, Taipei, Taiwan.
²⁵ Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.
²⁶ Department of Emergency Medicine, E-Da Hospital, I-Shou University School of Medicine for International Students, Taiwan.
²⁷ Department of Psychiatry, Tsyr-Huey Mental Hospital, Kaohsiung Jen-Ai's Home, Taiwan.
²⁸ Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.

PMID: 35450525
PMCID: PMC9886806
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; circadian rhythm; cognition; dementia; melatonin; network meta-analysis; psychiatry; quality of life.

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Figures

**Fig. (1)**
**Flowchart of the current network meta-analysis.** Figure 1) depicts the entire flowchart of the current network meta-analysis.

**Fig. (2)**
**The network structure of changes in cognitive function.** Figure 2) depicts the overall network structure of the current network meta-analysis of changes in cognitive function. The lines between nodes represent direct comparisons in various trials, and the size of each circle is proportional to the size of the population involved in each specific treatment. The thickness of the lines is proportional to the number of trials connected to the network.

**Fig. (3)**
**Forest plot of changes in cognitive function.** Figure 3) indicates that, when the effect size is more than zero, the specified treatment is associated with higher improvements in cognitive function in patients with Alzheimer’s dementia than placebos in the measurement of MMSE.

See this image and copyright information in PMC

References

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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

Affiliations

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

Authors

Affiliations

Abstract

Figures

References

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MeSH terms

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LinkOut - more resources

Full Text Sources

Medical