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

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

Prospect Clinic for Otorhinolaryngology Neurology, Kaohsiung 811, Taiwan; Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung 804, Taiwan; Department of Psychology, College of Medical and Health Science, Asia University, Taichung 413, Taiwan
Santi Antonio e Biagio e Cesare Arrigo Hospital
Kuang Tien General Hospital
Mind-Body Interface Laboratory (MBI-Lab) and Department of Psychiatry
Department of Radiology, The Affiliated Hospital of Guangzhou Medical University (GuangzhouHuiai Hospital), Guangzhou Medical University, Guangzhou, China.
Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.
Department of Haematological Medicine, King's College Hospital NHS Foundation Trust, London, UK; Department of Haematological Medicine, King's College London School of Medicine, London, UK; Division of Hematology, Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy.
Nanjing Medical University, Nanjing, China; Department of Pharmacology, School of Pharmacy, Nantong University, Nantong, China
An-Nan Hospital
Tainan Hospital
Department of Psychological Medicine
Health Psychology Section, Psychology Department, Institute of Psychology, Psychiatry and Neuroscience, King's College London, United Kingdom.
1Department of Hepatology, Imperial College London, London, UK. 2Institute of Liver Studies at King's College School of Medicine at King's College Hospital, London, UK. 3Institute of Human Health and Performance, University College London, London, UK. 4Department of Asthma Allergy and Lung Biology, King's College London, London, UK. 5Division of Critical Care Medicine, University of Alberta, Edmonton, Canada.
University of Ioannina School of Medicine; Stanford Prevention Research Center; Stanford University School of Medicine
Landseed International Hospital
Natl Taiwan Univ Hosp, National Taiwan University, National Taiwan University Hospital, Dept Lab Med
Chang Gung University
Psychiatric Health Strategic Research Centre, Deakin University, Geelong, VIC, Australia
NIHR Lecturer, Department of Psychological Medicine, Institute of Psychiatry, King's College London; and Head of Physiotherapy, Physiotherapy Department, South London and Maudsley NHS Foundation Trust, UK.
South London and Maudsley NHS Foundation Trust, Maudsley Hospital, London, SE5 8AZ, UK. [email protected].
Health, Social Care and Education, Anglia Ruskin University, Chelmsford, UK; Geriatrics Division, Department of Medicine-DIMED, University of Padova, Padova, Italy; Institute of clinical Research and Education in Medicine (IREM), Padova, Italy; Physiotherapy Department, South London and Maudsley NHS Foundation Trust, Denmark Hill, SE5 8AZ London, UK.
ANGLIA RUSKIN UNIVERSITY
New England Hernia Center, Chelmsford, MA, USA.
Research and Development Division
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Addiction Science, Kaohsiung Municipal Kai-Syuan Psychiatric Hospital, Kaohsiung, Taiwan.
I-Shou University School of Medicine for International Students
Department of Psychiatry, Tsyr-Huey Mental Hospital, Kaohsiung Jen-Ai's Home, Taiwan; WinShine Clinics in Specialty of Psychiatry, Kaohsiung, Taiwan.
Asia Univ, Asia University Taiwan, Dept Healthcare Adm

Research output: Contribution to journal › Article › peer-review

10 Citations (Scopus)

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. Trial Registration: The current study complies with the Institutional Review Board of the Tri-Service General Hospital (TSGHIRB: B-109-29) and had been registered in PROSPERO (CRD42020193088).

Original language	English
Pages (from-to)	1816-1833
Number of pages	18
Journal	Current Neuropharmacology
Volume	20
Issue number	10
Early online date	20 Apr 2022
DOIs	https://doi.org/10.2174/1570159X20666220420122322
Publication status	Published - Oct 2022

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10.2174/1570159X20666220420122322

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Tseng, P.-T., Zeng, B.-Y., Chen, Y.-W., Yang, C.-P., Su, K.-P., Chen, T.-Y., Wu, Y.-C., Tu, Y.-K., Lin, P.-Y., Carvalho, A. F., Stubbs, B., Matsuoka, Y. J., Li, D.-J., Liang, C.-S., Hsu, C.-W., Sun, C.-K., Cheng, Y.-S., Yeh, P.-Y., & Shiue, Y.-L. (2022). 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. Current Neuropharmacology, 20(10), 1816-1833. https://doi.org/10.2174/1570159X20666220420122322

@article{a04fc58fe6fa4efdadf62bda551519f1,

title = "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",

abstract = "Background: While Alzheimer{\textquoteright}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{\textquoteright}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. Trial Registration: The current study complies with the Institutional Review Board of the Tri-Service General Hospital (TSGHIRB: B-109-29) and had been registered in PROSPERO (CRD42020193088).",

author = "Ping-Tao Tseng and Bing-Yan Zeng and Yen-Wen Chen and Chun-Pai Yang and Kuan-Pin Su and Tien-Yu Chen and Yi-Cheng Wu and Yu-Kang Tu and Pao-Yen Lin and Carvalho, {Andre F} and Brendon Stubbs and Matsuoka, {Yutaka J} and Dian-Jeng Li and Chih-Sung Liang and Chih-Wei Hsu and Cheuk-Kwan Sun and Yu-Shian Cheng and Pin-Yang Yeh and Yow-Ling Shiue",

note = "Copyright{\textcopyright} Bentham Science Publishers; For any queries, please email at [email protected]. Publisher Copyright: {\textcopyright} 2022 Bentham Science Publishers.",

year = "2022",

month = oct,

doi = "10.2174/1570159X20666220420122322",

language = "English",

volume = "20",

pages = "1816--1833",

journal = "Current Neuropharmacology",

issn = "1875-6190",

publisher = "Bentham Science Publishers B.V.",

number = "10",

}

Tseng, P-T, Zeng, B-Y, Chen, Y-W, Yang, C-P, Su, K-P, Chen, T-Y, Wu, Y-C, Tu, Y-K, Lin, P-Y, Carvalho, AF, Stubbs, B, Matsuoka, YJ, Li, D-J, Liang, C-S, Hsu, C-W, Sun, C-K, Cheng, Y-S, Yeh, P-Y & Shiue, Y-L 2022, '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', Current Neuropharmacology, vol. 20, no. 10, pp. 1816-1833. https://doi.org/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. / Tseng, Ping-Tao; Zeng, Bing-Yan; Chen, Yen-Wen et al.
In: Current Neuropharmacology, Vol. 20, No. 10, 10.2022, p. 1816-1833.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - The Dose- and Duration-Dependent Association between Melatonin Treatment and Overall Cognition in Alzheimer's Dementia

T2 - A Network Meta-Analysis of Randomized Placebo-Controlled Trials

AU - Tseng, Ping-Tao

AU - Zeng, Bing-Yan

AU - Chen, Yen-Wen

AU - Yang, Chun-Pai

AU - Su, Kuan-Pin

AU - Chen, Tien-Yu

AU - Wu, Yi-Cheng

AU - Tu, Yu-Kang

AU - Lin, Pao-Yen

AU - Carvalho, Andre F

AU - Stubbs, Brendon

AU - Matsuoka, Yutaka J

AU - Li, Dian-Jeng

AU - Liang, Chih-Sung

AU - Hsu, Chih-Wei

AU - Sun, Cheuk-Kwan

AU - Cheng, Yu-Shian

AU - Yeh, Pin-Yang

AU - Shiue, Yow-Ling

PY - 2022/10

Y1 - 2022/10

N2 - 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. Trial Registration: The current study complies with the Institutional Review Board of the Tri-Service General Hospital (TSGHIRB: B-109-29) and had been registered in PROSPERO (CRD42020193088).

AB - 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. Trial Registration: The current study complies with the Institutional Review Board of the Tri-Service General Hospital (TSGHIRB: B-109-29) and had been registered in PROSPERO (CRD42020193088).

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U2 - 10.2174/1570159X20666220420122322

DO - 10.2174/1570159X20666220420122322

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SN - 1875-6190

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JO - Current Neuropharmacology

JF - Current Neuropharmacology

IS - 10

ER -

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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