The Relationship of Omega-3 Fatty Acids with Dementia and Cognitive Decline: Evidence from Prospective Cohort Studies of Supplementation, Dietary Intake, and Blood Markers

Bao-Zhen Wei; Lin Li; Cheng-Wen Dong; Chen-Chen Tan; Alzheimer’s Disease Neuroimaging Initiative; Wei Xu

doi:10.1016/j.ajcnut.2023.04.001

The Relationship of Omega-3 Fatty Acids with Dementia and Cognitive Decline: Evidence from Prospective Cohort Studies of Supplementation, Dietary Intake, and Blood Markers

Am J Clin Nutr. 2023 Jun;117(6):1096-1109. doi: 10.1016/j.ajcnut.2023.04.001. Epub 2023 Apr 5.

Authors

Bao-Zhen Wei¹, Lin Li², Cheng-Wen Dong³, Chen-Chen Tan⁴; Alzheimer’s Disease Neuroimaging Initiative; Wei Xu⁵

Affiliations

¹ Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China; The Affiliated Hospital of Qingdao University, Qingdao, China.
² Department of Neurology, Linyi People's Hospital, Qingdao University, Qingdao, China.
³ The Affiliated Hospital of Qingdao University, Qingdao, China.
⁴ Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China.
⁵ Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China. Electronic address: dr_xuwei@qdu.edu.cn.

Abstract

Previous data have linked omega-3 fatty acids with risk of dementia. We aimed to assess the longitudinal relationships of omega-3 polyunsaturated fatty acid intake as well as blood biomarkers with risk of Alzheimer's disease (AD), dementia, or cognitive decline. Longitudinal data were derived from 1135 participants without dementia (mean age = 73 y) in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort to evaluate the associations of omega-3 fatty acid supplementation and blood biomarkers with incident AD during the 6-y follow-up. A meta-analysis of published cohort studies was further conducted to test the longitudinal relationships of dietary intake of omega-3 and its peripheral markers with all-cause dementia or cognitive decline. Causal dose-response analyses were conducted using the robust error meta-regression model. In the ADNI cohort, long-term users of omega-3 fatty acid supplements exhibited a 64% reduced risk of AD (hazard ratio: 0.36, 95% confidence interval: 0.18, 0.72; P = 0.004). After incorporating 48 longitudinal studies involving 103,651 participants, a moderate-to-high level of evidence suggested that dietary intake of omega-3 fatty acids could lower risk of all-cause dementia or cognitive decline by ∼20%, especially for docosahexaenoic acid (DHA) intake (relative risk [RR]: 0.82, I² = 63.6%, P = 0.001) and for studies that were adjusted for apolipoprotein APOE ε4 status (RR: 0.83, I² = 65%, P = 0.006). Each increment of 0.1 g/d of DHA or eicosapentaenoic acid (EPA) intake was associated with an 8% ∼ 9.9% (P_linear < 0.0005) lower risk of cognitive decline. Moderate-to-high levels of evidence indicated that elevated levels of plasma EPA (RR: 0.88, I² = 38.1%) and erythrocyte membrane DHA (RR: 0.94, I² = 0.4%) were associated with a lower risk of cognitive decline. Dietary intake or long-term supplementation of omega-3 fatty acids may help reduce risk of AD or cognitive decline.

Keywords: AD; biomarker; cognitive decline; dementia; dietary; omega-3 fatty acid.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Aged
Alzheimer Disease* / prevention & control
Cognitive Dysfunction* / prevention & control
Cohort Studies
Dietary Supplements
Docosahexaenoic Acids
Eating
Eicosapentaenoic Acid
Fatty Acids, Omega-3*
Humans
Prospective Studies

Substances

Docosahexaenoic Acids
Eicosapentaenoic Acid
Fatty Acids, Omega-3

Grants and funding

U01 AG024904/AG/NIA NIH HHS/United States