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

• Published in: Brain, behavior, and immunity Vol. 111; pp. 352 - 364
• Main Authors: Tseng, Ping-Tao, Zeng, Bing-Syuan, Suen, Mein-Woei, Wu, Yi-Cheng, Correll, Christoph U, Zeng, Bing-Yan, Kuo, John S., Chen, Yen-Wen, Chen, Tien-Yu, Tu, Yu-Kang, Lin, Pao-Yen, Carvalho, Andre F., Stubbs, Brendon, Li, Dian-Jeng, Liang, Chih-Sung, Hsu, Chih-Wei, Sun, Cheuk-Kwan, Cheng, Yu-Shian, Yeh, Pin-Yang, Wu, Ming-Kung, Shiue, Yow-Ling, Su, Kuan-Pin
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.07.2023
• Subjects: Alzheimer Disease - drug therapy; Alzheimer’s dementia; Anti-Inflammatory Agents - therapeutic use; Cognition; Dementia; Eicosapentaenoic Acid - pharmacology; Eicosapentaenoic Acid - therapeutic use; Fatty Acids, Omega-3 - therapeutic use; Humans; Network Meta-Analysis; Omega-3 fatty acid; Oxidation; Randomized Controlled Trials as Topic; Trial registration: PROSPERO (CRD42022336051); Med-ExHigh-Mem; Cognition; ExHi-n3PUFA-DHA; Hi-n3PUFA-EPA + ALA; Med-High-Mem + Med-High-Don; RBC; omega-3 PUFA; Med-High-Mem; Med-High-Gal; Long-High-Riv; Med-ExHigh-Don; Med-Med-Don; AD; ADAS-cog; Short-Low-Gal; SMD; Med-High-Don; Med-Low-RivPatch; Med-Med-Gal; Me-n3PUFA-pDHA; DHA; Med-ExHigh-Riv; Med-Low-Riv; Med-High-RivPatch; Dementia; RCT; Network meta-analysis; Med-High-Mem + Med-Low-Gal; Med-High-Riv; 95%Cis; Med-High-Mem + Med-Med-Riv; Pla; ExLong-Med-Gal; Short-High-Don; MMSE; Short-Med-Don; Oxidation; Hi-n3PUFA-EPA; Short-High-Gal; Short-High-Mem; Short-High-Riv; NMA; OR; Trial registration: PROSPERO (CRD42022336051); EPA/DHA ratio; PRISMA; Short-Med-Gal; Alzheimer’s dementia; MCI; ALA; EPA; Omega-3 fatty acid; Sou; ExLong-High-Mem
• ISSN: 0889-1591; 1090-2139
• DOI: 10.1016/j.bbi.2023.04.017

•High dose EPA-dominant omega-3 PUFAs plus antioxidants best improved cognition.•Omega-3 PUFAs has similar acceptability and safety profiles compared to placebo.•This study supports the neurotherapeutic effects of omega-3 PUFAs in AD patients. 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.