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February 28, 2012; 78 (9) Articles

Red blood cell omega-3 fatty acid levels and markers of accelerated brain aging

Z.S. Tan, W.S. Harris, A.S. Beiser, R. Au, J.J. Himali, S. Debette, A. Pikula, C. DeCarli, P.A. Wolf, R.S. Vasan, S.J. Robins, S. Seshadri
First published February 27, 2012, DOI: https://doi.org/10.1212/WNL.0b013e318249f6a9
Z.S. Tan
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W.S. Harris
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A.S. Beiser
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R. Au
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Citation
Red blood cell omega-3 fatty acid levels and markers of accelerated brain aging
Z.S. Tan, W.S. Harris, A.S. Beiser, R. Au, J.J. Himali, S. Debette, A. Pikula, C. DeCarli, P.A. Wolf, R.S. Vasan, S.J. Robins, S. Seshadri
Neurology Feb 2012, 78 (9) 658-664; DOI: 10.1212/WNL.0b013e318249f6a9

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Abstract

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 = 1,575; 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.

GLOSSARY

AD=
Alzheimer disease;
BMI=
body mass index;
DHA=
docosahexaenoic acid;
DM=
diabetes mellitus;
EPA=
eicosapentaenoic acid;
LM-d=
delayed recall components of the Logical Memory test;
NP=
neuropsychological;
PAI=
physical activity index;
PUFA=
polyunsaturated fatty acid;
RBC=
red blood cell;
SBP=
systolic blood pressure;
SCI=
silent cerebral infarct;
SIM=
Similarities test;
TCBV=
total cerebral brain volume;
THV=
temporal horn volume;
VR-d=
delayed recall component of the Visual Reproductions test;
WMHV=
white matter hyperintensity volume

Footnotes

  • Study funding: Supported by the Framingham Heart Study's National Heart, Lung, and Blood Institute contract (N01-HC-25195) and by grants from the NHLBI: R01 HL089590 and National Institute on Aging (R01 AG16495, AG 033040, AG08122, AG033193, and AG031287).

  • Supplemental data at www.neurology.org

  • Received June 16, 2011.
  • Accepted October 26, 2011.
  • Copyright © 2012 by AAN Enterprises, Inc.
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Letters: Rapid online correspondence

  • Omega-3 fatty acids such as docosahexaenoic acid activate retinoid X receptor pathways inducing ApoE expression and clearance of Beta-Amyloid with improved cognitive performance and inhibition of brain aging.
    • Steven R. Brenner, Staff physician, St. Louis University Dept. of Neurology and PsychiatrySBren20979@aol.com
    • St. Louis, MO
    Submitted March 16, 2012
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