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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

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posted on 2024-04-19, 13:01 authored by 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

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. 

History

Refereed

  • Yes

Volume

111

Page range

352-364

Publication title

Brain, Behavior, and Immunity

ISSN

0889-1591

Publisher

Elsevier BV

File version

  • Published version

Language

  • eng

Legacy Faculty/School/Department

Faculty of Health, Medicine and Social Care