Docosahexaenoic Acid Levels and Omega-3 Index, but Not Eicosapentaenoic Acid Levels, Are Associated With Improved Cognition in Cognitively Healthy Subjects With Coronary Artery Disease (2025)

. Author manuscript; available in PMC: 2023 Nov 22.

Published in final edited form as: Arterioscler Thromb Vasc Biol. 2022 Dec 29;43(2):382–384. doi: 10.1161/ATVBAHA.122.318569

Georges Chedid

^1,^*, Abdulaziz Malik

^2,^*, Maral Amangurbanova

³, Haitham Khraishah

⁴, Francine K Welty

METHODS

CAD subjects on statin therapy were randomized to 3.36 g of EPA+DHA daily for 30 months or none. Cognitive function was assessed using standardized neuropsychological cognitive tests as previously described.¹ Plasma levels of DHA and EPA were measured with gas chromatography; the omega-3 fatty acid index was calculated as percent EPA+DHA of total fatty acids.

RESULTS

A total of 233 subjects had cognitive testing at baseline and 12 and 30 months and plasma levels of EPA and DHA measured. Mean (SD) age was 63.4 (7.5) years (83% male). No significant differences were observed in baseline characteristics in the EPA+DHA and control groups.¹

After adjustment for age, sex, body mass index, diabetes, hypertension, and statin use, the Figure [A] reports that subjects with DHA levels above the median (85 μg/mL) were associated with improvement in two cognitive function tests: controlled oral word association test 1, a measure of verbal fluency, language and memory, and TMT A, a test of visual-motor coordination whereas EPA levels were not associated. An omega-3 fatty acid index ≥ 4% had the strongest association for controlled oral word association test 1 and was also associated with significant improvement in the digit symbol substitution test, which measures psychomotor speed, sustained attention, response speed and visual-motor coordination, at both 12 and 30 months compared to baseline. In the Figure [B], those with an omega-3 fatty acid index ≥4% had significant improvement at 12 and 30 months (P<0.001) in the digit symbol substitution test score compared to their baseline, supporting a delay in cognitive aging of at least 30 months compared to the unchanged scores in those with an index <4%.

DISCUSSION

Achieved levels of DHA are more important than EPA for improvement in cognitive function in cognitively healthy, older adults with stable CAD; however, both EPA and DHA combined lead to sustained improvement over a 30-month period compared to control. The association of DHA levels but not EPA alone may be due to the fact that DHA comprises ≈25% of neuronal membranes in the human cerebral cortex whereas EPA is almost undetectable.² Importantly, the lack of the DHA transporter, Mfsd2a (major facilitator superfamily domain-containing protein 2a), resulted in markedly reduced levels of DHA in brains of Mfsd2a knockout mice and development of cognitive deficits and neuronal cell loss in hippocampus and cerebellum, providing strong support for the role of DHA in cognitive function.³ The lack of association with EPA levels is in agreement with the Chicago Memory and Aging project, which reported that total dietary intake of omega-3 fatty acids and DHA were associated with reduced risk of Alzheimer disease but EPA was not.⁴ The current findings have potential public health significance and support the use of combined EPA and DHA in cognitively healthy subjects to improve cognitive function that could potentially prevent or delay cognitive decline in an aging population. These findings are especially important for patients with CAD as CAD has been implicated as a risk factor in dementia.

Sources of Funding

NIH SCCOR provided grant to F.K. Welty: P50 HL083813.

Nonstandard Abbreviations and Acronyms

CAD: coronary artery disease
DHA: docosahexaenoic acid
EPA: eicosapentaenoic acid
MFSD2a: major facilitator superfamily domain-containing protein 2a
TMT: trail making test

Footnotes

Disclosures

None.

Contributor Information

Georges Chedid, The Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, Byblos, Lebanon.

Abdulaziz Malik, Division of Cardiology, Beth Israel Deaconess Medical Center, Boston, MA.

Maral Amangurbanova, Division of Cardiology, Beth Israel Deaconess Medical Center, Boston, MA.

Haitham Khraishah, Division of Cardiology, Beth Israel Deaconess Medical Center, Boston, MA.

Francine K. Welty, Division of Cardiology, Beth Israel Deaconess Medical Center, Boston, MA

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