Red blood cell omega-3 fatty acid levels and markers of accelerated brain aging
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OBJECTIVE: Higher dietary intake and circulating levels of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have been related to a reduced risk for dementia, but the pathways underlying this association remain unclear. We examined the cross-sectional relation of red blood cell (RBC) fatty acid levels to subclinical imaging and cognitive markers of dementia risk in a middle-aged to elderly community-based cohort. METHODS: We related RBC DHA and EPA levels in dementia-free Framingham Study participants (n = 1575; 854 women, age 67 ± 9 years) to performance on cognitive tests and to volumetric brain MRI, with serial adjustments for age, sex, and education (model A, primary model), additionally for APOE ε4 and plasma homocysteine (model B), and also for physical activity and body mass index (model C), or for traditional vascular risk factors (model D). RESULTS: Participants with RBC DHA levels in the lowest quartile (Q1) when compared to others (Q2-4) had lower total brain and greater white matter hyperintensity volumes (for model A: β ± SE = -0.49 ± 0.19; p = 0.009, and 0.12 ± 0.06; p = 0.049, respectively) with persistence of the association with total brain volume in multivariable analyses. Participants with lower DHA and ω-3 index (RBC DHA+EPA) levels (Q1 vs. Q2-4) also had lower scores on tests of visual memory (β ± SE = -0.47 ± 0.18; p = 0.008), executive function (β ± SE = -0.07 ± 0.03; p = 0.004), and abstract thinking (β ± SE = -0.52 ± 0.18; p = 0.004) in model A, the results remaining significant in all models. CONCLUSION: Lower RBC DHA levels are associated with smaller brain volumes and a "vascular" pattern of cognitive impairment even in persons free of clinical dementia.
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A higher omega-3 index was associated with a greater hippocampal volume in the Women's Health Initiative Memory Study and with a larger brain volume and improved cognitive test scores in the Framingham offspring cohort-based study.
“A higher omega-3 index was associated with a greater hippocampal volume in the Women's Health Initiative Memory Study [80] and with a larger brain volume and improved cognitive test scores in the Framingham offspring cohort-based study [81].”
From Role of n-3 long-chain polyunsaturated fatty acids in human nutrition and health: Review of recent studies and recommendations (2021) · cites this paper as [81]
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- Authors
- Tan, Z. S., Harris, W. S., Beiser, A. S., Au, R., Himali, J. J., Debette, S., Pikula, A., DeCarli, C., Wolf, P. A., Vasan, R. S., Robins, S. J., & Seshadri, S.
- Affiliations
- Boston University (US)
- ORCID
- Venue
- Neurology
- Published
- 2012-02-28
- Volume
- 78
- Issue
- 9
- Pages
- 658-664
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC3286229
- OpenAlex
- W2148201096
- Cited by
- 265
- References
- 40
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 13 · 2023: 14 · 2022: 14 · 2021: 21 · 2020: 29 · 2019: 11 · 2018: 23 · 2017: 19 · 2016: 16 · 2015: 22 · 2014: 31 · 2013: 23 · 2012: 9
- FWCI
- 25.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (n01hc25195-41-0-1)
- National Institute on Aging (R01-AG-16495, R01AG031287, AG031287, AG08122, AG033193, R01AG033040, R01AG016495, AG 033040, R01AG033193, R01AG008122)
- National Heart, Lung, and Blood Institute (N01‐HC25195, AG08122, AG031287, R01HL089590, AG16495, AG033193)
- National Institute of Neurological Disorders and Stroke (R01NS017950)
- 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, docosahexaenoic acid, eicosapentaenoic acid, red blood cell fatty acids, brain aging, dementia risk, white matter hyperintensities, brain volume, cognitive impairment, visual memory, executive function, abstract thinking, APOE ε4, homocysteine, Framingham Heart Study
- MeSH terms
- Aged, Aged, 80 and over, Aging, Alzheimer Disease, Brain, Cognition, Dementia, Erythrocytes, Female, Humans, Male, Middle Aged, Neuropsychological Tests, Risk Factors, Fatty Acids, Omega-3
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