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
Journal
Brain, behavior, and immunity
Journal Volume
111
Pages
352
Date Issued
2023-07
Author(s)
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
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
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.
Subjects
Alzheimer’s dementia; Cognition; Dementia; Network meta-analysis; Omega-3 fatty acid; Oxidation; Trial registration: PROSPERO (CRD42022336051)
SDGs
Publisher
Elsevier Ltd
Type
journal article