The Relationship of Omega-3 Fatty Acids with Dementia and Cognitive Decline: Evidence from Prospective Cohort Studies of Supplementation, Dietary Intake, and Blood Markers
Open accessAbstract
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, I 2 = 63.6%, P = 0.001) and for studies that were adjusted for apolipoprotein APOE ε4 status (RR: 0.83, I 2 = 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, I 2 = 38.1%) and erythrocyte membrane DHA (RR: 0.94, I 2 = 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.
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Higher dietary intake of omega-3 fatty acids is associated with reduced risk of dementia and cognitive decline, while pro-inflammatory omega-6 metabolites are positively correlated with Alzheimer's disease pathologies.
“Conversely, the pro-inflammatory metabolites of omega-6 fatty acids are positively correlated with AD pathologies (Fig. 3e).438 Indeed, a higher dietary intake of omega-3 fatty acids is associated with a reduced risk of dementia and cognitive decline.439”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [439]
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Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases
Loh, J. S., Mak, W. Q., Tan, L. K. S., Ng, C. X., Chan, H. H., Yeow, S. H., Foo, J. B., Ong, Y. S., How, C. W., & Khaw, K. Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01743-1 · Cited by 1,193 · see citing works
- Authors
- Wei, B.-Z., Li, L., Dong, C.-W., Tan, C.-C., & Xu, W.
- Affiliations
- Qingdao University (CN)
- Affiliated Hospital of Qingdao University (CN)
- Corresponding author
- Xu, Wei
- Venue
- The American Journal of Clinical Nutrition
- Publisher
- Elsevier BV
- Published
- 2023-06
- Volume
- 117
- Issue
- 6
- Pages
- 1096-1109
- ISSN
- 0002-9165 (ISSN-L)
- PMC
- PMC10447496
- OpenAlex
- W4362638486
- Cited by
- 169
- References
- 10
- Citations by year
- 2026: 57 · 2025: 73 · 2024: 33 · 2023: 6
- FWCI
- 29.49
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- American Journal of Clinical Nutrition (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (82001136)
- National Institutes of Health (5u01ag024904-10)
- National Institute on Aging (U01-AG-024904)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
- Keywords
- omega-3 fatty acids, dementia, cognitive decline, Alzheimer's disease, docosahexaenoic acid, eicosapentaenoic acid, omega-3 supplementation, dietary intake, blood biomarkers, APOE ε4, dose-response relationship, ADNI cohort, meta-regression, prospective cohort, risk mitigation
- MeSH terms
- Aged, Alzheimer Disease, Docosahexaenoic Acids, Eating, Humans, Prospective Studies, Eicosapentaenoic Acid, Cohort Studies, Fatty Acids, Omega-3, Dietary Supplements, Cognitive Dysfunction
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