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; Bing-Syuan Zeng; Mein-Woei Suen; Yi-Cheng Wu; Christoph U Correll; Bing-Yan Zeng; John S Kuo; Yen-Wen Chen; Tien-Yu Chen; Yu-Kang Tu; Pao-Yen Lin; Andre F Carvalho; Brendon Stubbs; Dian-Jeng Li; Chih-Sung Liang; Chih-Wei Hsu; Cheuk-Kwan Sun; Yu-Shian Cheng; Pin-Yang Yeh; Ming-Kung Wu; Yow-Ling Shiue; Kuan-Pin Su

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

Brain Behav Immun. 2023 Jul:111:352-364. doi: 10.1016/j.bbi.2023.04.017. Epub 2023 May 6.

Authors

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

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).

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease* / drug therapy
Anti-Inflammatory Agents / therapeutic use
Cognition
Eicosapentaenoic Acid / pharmacology
Eicosapentaenoic Acid / therapeutic use
Fatty Acids, Omega-3* / therapeutic use
Humans
Network Meta-Analysis
Randomized Controlled Trials as Topic

Substances

Eicosapentaenoic Acid
Fatty Acids, Omega-3
Anti-Inflammatory Agents

Grants and funding

ICA-CL-2017-03-001/DH_/Department of Health/United Kingdom