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

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

^*Corresponding author for this work

School of Medicine

Research output: Contribution to journal › Journal Article › peer-review

19 Scopus citations

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.

Original language	English
Pages (from-to)	352-364
Number of pages	13
Journal	Brain, Behavior, and Immunity
Volume	111
DOIs	https://doi.org/10.1016/j.bbi.2023.04.017
State	Published - 07 2023

Bibliographical note

Publisher Copyright:
© 2023 Elsevier Inc.

Keywords

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

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Tseng, P. T., Zeng, B. S., Suen, M. W., Wu, Y. C., Correll, C. U., Zeng, B. Y., Kuo, J. S., Chen, Y. W., Chen, T. Y., Tu, Y. K., Lin, P. Y., Carvalho, A. F., Stubbs, B., Li, D. J., Liang, C. S., Hsu, C. W., Sun, C. K., Cheng, Y. S., Yeh, P. Y., ... Su, K. P. (2023). 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, Behavior, and Immunity, 111, 352-364. https://doi.org/10.1016/j.bbi.2023.04.017

@article{aedc9baa7b4e4d33a711939f3aea0e96,

title = "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",

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)",

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

note = "Publisher Copyright: {\textcopyright} 2023 Elsevier Inc.",

year = "2023",

month = jul,

doi = "10.1016/j.bbi.2023.04.017",

language = "英语",

volume = "111",

pages = "352--364",

journal = "Brain, Behavior, and Immunity",

issn = "0889-1591",

publisher = "Academic Press Inc.",

}

Tseng, PT, Zeng, BS, Suen, MW, Wu, YC, Correll, CU, Zeng, BY, Kuo, JS, Chen, YW, Chen, TY, Tu, YK, Lin, PY, Carvalho, AF, Stubbs, B, Li, DJ, Liang, CS, Hsu, CW, Sun, CK, Cheng, YS, Yeh, PY, Wu, MK, Shiue, YL & Su, KP 2023, '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, Behavior, and Immunity, vol. 111, pp. 352-364. https://doi.org/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. / Tseng, Ping Tao; Zeng, Bing Syuan; Suen, Mein Woei et al.
In: Brain, Behavior, and Immunity, Vol. 111, 07.2023, p. 352-364.

Research output: Contribution to journal › Journal Article › peer-review

TY - JOUR

T1 - Efficacy and acceptability of anti-inflammatory eicosapentaenoic acid for cognitive function in Alzheimer's dementia

T2 - A network meta-analysis of randomized, placebo-controlled trials with omega-3 fatty acids and FDA-approved pharmacotherapy

AU - Tseng, Ping Tao

AU - Zeng, Bing Syuan

AU - Suen, Mein Woei

AU - Wu, Yi Cheng

AU - Correll, Christoph U.

AU - Zeng, Bing Yan

AU - Kuo, John S.

AU - Chen, Yen Wen

AU - Chen, Tien Yu

AU - Tu, Yu Kang

AU - Lin, Pao Yen

AU - Carvalho, Andre F.

AU - Stubbs, Brendon

AU - Li, Dian Jeng

AU - Liang, Chih Sung

AU - Hsu, Chih Wei

AU - Sun, Cheuk Kwan

AU - Cheng, Yu Shian

AU - Yeh, Pin Yang

AU - Wu, Ming Kung

AU - Shiue, Yow Ling

AU - Su, Kuan Pin

PY - 2023/7

Y1 - 2023/7

N2 - 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.

AB - 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.

KW - Alzheimer's dementia

KW - Cognition

KW - Dementia

KW - Network meta-analysis

KW - Omega-3 fatty acid

KW - Oxidation

KW - Trial registration: PROSPERO (CRD42022336051)

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U2 - 10.1016/j.bbi.2023.04.017

DO - 10.1016/j.bbi.2023.04.017

M3 - 文章

C2 - 37150266

AN - SCOPUS:85159610963

SN - 0889-1591

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SP - 352

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JO - Brain, Behavior, and Immunity

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ER -

Tseng PT, Zeng BS, Suen MW, Wu YC, Correll CU, Zeng BY et al. 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, Behavior, and Immunity. 2023 Jul;111:352-364. 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

Abstract

Bibliographical note

Keywords

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