Efficacy and acceptability of anti-inflammatory eicosapentaenoic acid for cognitive function in Alzheimer's dementia: A network meta-analysis of randomized, placebo-controlled trials with omega-3 fatty acids and FDA-approved pharmacotherapy

Ping-Tao Tseng¹, Bing-Syuan Zeng², Mein-Woei Suen³, Yi-Cheng Wu⁴, Christoph U Correll⁵, Bing-Yan Zeng⁶, John S Kuo⁷, Yen-Wen Chen⁸, Tien-Yu Chen⁹, Yu-Kang Tu¹⁰, Pao-Yen Lin¹¹, Andre F Carvalho¹², Brendon Stubbs¹³, Dian-Jeng Li¹⁴, Chih-Sung Liang¹⁵, Chih-Wei Hsu¹⁶, Cheuk-Kwan Sun¹⁷, Yu-Shian Cheng¹⁸, Pin-Yang Yeh¹⁹, Ming-Kung Wu²⁰, Yow-Ling Shiue²¹, Kuan-Pin Su²²

Affiliations

¹ Department of Psychology, College of Medical and Health Science, Asia University, Taichung, Taiwan; Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan; Prospect Clinic for Otorhinolaryngology & Neurology, Kaohsiung, Taiwan; Institute of Precision Medicine, National Sun Yat-sen University, Kaohsiung City, Taiwan.
² Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan; Department of Internal Medicine, E-Da Cancer Hospital, I-Shou University, Kaohsiung, Taiwan.
³ Department of Psychology, College of Medical and Health Science, Asia University, Taichung, Taiwan; Gender Equality Education and Research Center, Asia University, Taichung, Taiwan; Department of Medical Research, Asia University Hospital, Asia University, Taichung, Taiwan; Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan.
⁴ Department of Sports Medicine, Landseed International Hospital, Taoyuan, Taiwan.
⁵ Department of Psychiatry, The Zucker Hillside Hospital, Northwell Health, Glen Oaks, NY, USA; Department of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA; Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin Berlin, Berlin, Germany.
⁶ Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan; Department of Internal Medicine, E-Da Dachang Hospital, I-Shou University, Kaohsiung, Taiwan.
⁷ Neuroscience and Brain Disease Center, China Medical University, Taichung, Taiwan; Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
⁸ Prospect Clinic for Otorhinolaryngology & Neurology, Kaohsiung, Taiwan.
⁹ Department of Psychiatry, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan; Institute of Brain Science, National Yang Ming Chiao Tung University, Taipei 112, Taiwan.
¹⁰ Institute of Epidemiology & Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan.
¹¹ Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; Institute for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
¹² Senior Researcher, IMPACT (Innovation in Mental and Physical Health and Clinical Treatment) Strategic Research Centre, School of Medicine, Barwon Health, Deakin University, Geelong, VIC, Australia.
¹³ Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; Physiotherapy Department, South London and Maudsley NHS Foundation Trust, London, UK; Faculty of Health, Social Care Medicine and Education, Anglia Ruskin University, Chelmsford, UK.
¹⁴ Department of Addiction Science, Kaohsiung Municipal Kai-Syuan Psychiatric Hospital, Kaohsiung City, Taiwan.
¹⁵ Department of Psychiatry, Beitou Branch, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan; Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.
¹⁶ Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
¹⁷ Department of Emergency Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan; School of Medicine for International Students, I-Shou University, Kaohsiung, Taiwan.
¹⁸ Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan; Department of Psychiatry, Tsyr-Huey Mental Hospital, Kaohsiung Jen-Ai's Home, Taiwan.
¹⁹ Department of Psychology, College of Medical and Health Science, Asia University, Taichung, Taiwan; Clinical Psychology Center, Asia University Hospital, Taichung, Taiwan.
²⁰ Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. Electronic address: mingkung180@gmail.com.
²¹ Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan. Electronic address: shirley@imst.nsysu.edu.tw.
²² Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; Mind-Body Interface Research Center (MBI-Lab), China Medical University Hospital, Taichung, Taiwan; College of Medicine, China Medical University, Taichung, Taiwan; An-Nan Hospital, China Medical University, Tainan, Taiwan. Electronic address: cobolsu@gmail.com.

PMID: 37150266
DOI: 10.1016/j.bbi.2023.04.017

Efficacy and acceptability of anti-inflammatory eicosapentaenoic acid for cognitive function in Alzheimer's dementia: A network meta-analysis of randomized, placebo-controlled trials with omega-3 fatty acids and FDA-approved pharmacotherapy

Ping-Tao Tseng et al. Brain Behav Immun. 2023 Jul.

. 2023 Jul:111:352-364.

doi: 10.1016/j.bbi.2023.04.017. Epub 2023 May 6.

Authors

Affiliations

¹ Department of Psychology, College of Medical and Health Science, Asia University, Taichung, Taiwan; Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan; Prospect Clinic for Otorhinolaryngology & Neurology, Kaohsiung, Taiwan; Institute of Precision Medicine, National Sun Yat-sen University, Kaohsiung City, Taiwan.
² Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan; Department of Internal Medicine, E-Da Cancer Hospital, I-Shou University, Kaohsiung, Taiwan.
³ Department of Psychology, College of Medical and Health Science, Asia University, Taichung, Taiwan; Gender Equality Education and Research Center, Asia University, Taichung, Taiwan; Department of Medical Research, Asia University Hospital, Asia University, Taichung, Taiwan; Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan.
⁴ Department of Sports Medicine, Landseed International Hospital, Taoyuan, Taiwan.
⁵ Department of Psychiatry, The Zucker Hillside Hospital, Northwell Health, Glen Oaks, NY, USA; Department of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA; Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin Berlin, Berlin, Germany.
⁶ Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan; Department of Internal Medicine, E-Da Dachang Hospital, I-Shou University, Kaohsiung, Taiwan.
⁷ Neuroscience and Brain Disease Center, China Medical University, Taichung, Taiwan; Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
⁸ Prospect Clinic for Otorhinolaryngology & Neurology, Kaohsiung, Taiwan.
⁹ Department of Psychiatry, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan; Institute of Brain Science, National Yang Ming Chiao Tung University, Taipei 112, Taiwan.
¹⁰ Institute of Epidemiology & Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan.
¹¹ Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; Institute for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
¹² Senior Researcher, IMPACT (Innovation in Mental and Physical Health and Clinical Treatment) Strategic Research Centre, School of Medicine, Barwon Health, Deakin University, Geelong, VIC, Australia.
¹³ Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; Physiotherapy Department, South London and Maudsley NHS Foundation Trust, London, UK; Faculty of Health, Social Care Medicine and Education, Anglia Ruskin University, Chelmsford, UK.
¹⁴ Department of Addiction Science, Kaohsiung Municipal Kai-Syuan Psychiatric Hospital, Kaohsiung City, Taiwan.
¹⁵ Department of Psychiatry, Beitou Branch, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan; Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.
¹⁶ Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
¹⁷ Department of Emergency Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan; School of Medicine for International Students, I-Shou University, Kaohsiung, Taiwan.
¹⁸ Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan; Department of Psychiatry, Tsyr-Huey Mental Hospital, Kaohsiung Jen-Ai's Home, Taiwan.
¹⁹ Department of Psychology, College of Medical and Health Science, Asia University, Taichung, Taiwan; Clinical Psychology Center, Asia University Hospital, Taichung, Taiwan.
²⁰ Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. Electronic address: mingkung180@gmail.com.
²¹ Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan. Electronic address: shirley@imst.nsysu.edu.tw.
²² Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; Mind-Body Interface Research Center (MBI-Lab), China Medical University Hospital, Taichung, Taiwan; College of Medicine, China Medical University, Taichung, Taiwan; An-Nan Hospital, China Medical University, Tainan, Taiwan. Electronic address: cobolsu@gmail.com.

PMID: 37150266
DOI: 10.1016/j.bbi.2023.04.017

Abstract

Alzheimer's dementia (AD) is a major contributor to global disability, and effective therapies to modify disease progression are currently lacking. The neuro-inflammatory theory is a potential etiology underlying this neurodegenerative disease. Previous randomized, controlled trials (RCTs) have provided inconclusive results regarding efficacy of omega-3 polyunsaturated fatty acids (PUFAs) regimens, which might provide anti-inflammatory benefits in the management of AD, in improving cognitive function among participants with AD. The objective of this frequentist-model based network meta-analysis (NMA) was to evaluate the potential advantages of omega-3 PUFAs and currently FDA-approved medications for AD on overall cognitive function in AD individuals. The primary outcomes were: (1) changes in cognitive function, and (2) acceptability, which refers to all-cause discontinuation. Additionally, secondary outcomes included quality of life, behavioral disturbances and safety/tolerability, which was assessed through the frequency of any reported adverse event. This NMA included 52 RCTs (6 with omega-3 PUFAs and 46 with FDA-approved medications) involving 21,111 participants. The results showed that long-term high-dose (1500-2000 mg/day) of eicosapentaenoic acid (EPA)-dominant omega-3 PUFAs augmented with anti-oxidants had the highest potential for cognitive improvement among all investigated treatments [standardized mean difference = 3.00, 95% confidence intervals (95 %CIs) = 1.84-4.16]. Compared to placebo, omega-3 PUFAs had similar acceptability [odds ratio (OR) = 0.46, 95 %CIs = 0.04 to 5.87] and safety profiles (OR = 1.24, 95 %CIs = 0.66 to 2.33)o. These findings support the potential neurotherapeutic effects of high dosage EPA-dominant omega-3 PUFAs for the amelioration of cognitive decline in patients with AD. Future large-scale, long-term RCTs should focus on different dosages of EPA-dominant omega-3 PUFAs regimens on improving cognitive dysfunction in patients with AD at different levels of inflammatory status and psychopathology.

Keywords: Alzheimer’s dementia; Cognition; Dementia; Network meta-analysis; Omega-3 fatty acid; Oxidation; Trial registration: PROSPERO (CRD42022336051).

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Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. CU Correll has been a consultant and/or advisor to or has received honoraria from: AbbVie, Acadia, Alkermes, Allergan, Angelini, Aristo, Boehringer-Ingelheim, Cardio Diagnostics, Cerevel, CNX Therapeutics, Compass Pathways, Darnitsa, Gedeon Richter, Hikma, Holmusk, IntraCellular Therapies, Janssen/J&J, Karuna, LB Pharma, Lundbeck, MedAvante-ProPhase, MedInCell, Merck, Mindpax, Mitsubishi Tanabe Pharma, Mylan, Neurocrine, Newron, Noven, Otsuka, Pharmabrain, PPD Biotech, Recordati, Relmada, Reviva, Rovi, Seqirus, SK Life Science, Sunovion, Sun Pharma, Supernus, Takeda, Teva, and Viatris. He provided expert testimony for Janssen and Otsuka. He served on a Data Safety Monitoring Board for Lundbeck, Relmada, Reviva, Rovi, Supernus, and Teva. He has received grant support from Janssen and Takeda. He received royalties from UpToDate and is also a stock option holder of Cardio Diagnostics, Mindpax, LB Pharma and Quantic. The other authors declare no conflict of interest, financial or otherwise.

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Efficacy and acceptability of anti-inflammatory eicosapentaenoic acid for cognitive function in Alzheimer's dementia: A network meta-analysis of randomized, placebo-controlled trials with omega-3 fatty acids and FDA-approved pharmacotherapy

Affiliations

Efficacy and acceptability of anti-inflammatory eicosapentaenoic acid for cognitive function in Alzheimer's dementia: A network meta-analysis of randomized, placebo-controlled trials with omega-3 fatty acids and FDA-approved pharmacotherapy

Authors

Affiliations

Abstract

Conflict of interest statement

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MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Research Materials