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Randomized Controlled Trial
. 2014 Feb 4;82(5):435-42.
doi: 10.1212/WNL.0000000000000080. Epub 2014 Jan 22.

Higher RBC EPA + DHA Corresponds With Larger Total Brain and Hippocampal Volumes: WHIMS-MRI Study

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Randomized Controlled Trial

Higher RBC EPA + DHA Corresponds With Larger Total Brain and Hippocampal Volumes: WHIMS-MRI Study

James V Pottala et al. Neurology. .
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Objective: To test whether red blood cell (RBC) levels of marine omega-3 fatty acids measured in the Women's Health Initiative Memory Study were related to MRI brain volumes measured 8 years later.

Methods: RBC eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and MRI brain volumes were assessed in 1,111 postmenopausal women from the Women's Health Initiative Memory Study. The endpoints were total brain volume and anatomical regions. Linear mixed models included multiple imputations of fatty acids and were adjusted for hormone therapy, time since randomization, demographics, intracranial volume, and cardiovascular disease risk factors.

Results: In fully adjusted models, a 1 SD greater RBC EPA + DHA (omega-3 index) level was correlated with 2.1 cm(3) larger brain volume (p = 0.048). DHA was marginally correlated (p = 0.063) with total brain volume while EPA was less so (p = 0.11). There were no correlations between ischemic lesion volumes and EPA, DHA, or EPA + DHA. A 1 SD greater omega-3 index was correlated with greater hippocampal volume (50 mm(3), p = 0.036) in fully adjusted models. Comparing the fourth quartile vs the first quartile of the omega-3 index confirmed greater hippocampal volume (159 mm(3), p = 0.034).

Conclusion: A higher omega-3 index was correlated with larger total normal brain volume and hippocampal volume in postmenopausal women measured 8 years later. While normal aging results in overall brain atrophy, lower omega-3 index may signal increased risk of hippocampal atrophy. Future studies should examine whether maintaining higher RBC EPA + DHA levels slows the rate of hippocampal or overall brain atrophy.


Figure 1
Figure 1. Mean normal (A) and ischemic (B) lesion brain volumes in cubic centimeters by anatomical region
Figure 2
Figure 2. Mean normal hippocampal brain volume in cubic centimeters by omega-3 index using linear regression with 95% confidence bands
The fully adjusted model has a slightly attenuated slope compared with the unadjusted model, but reduced variability; a 3.2% greater omega-3 index is correlated with 100 mm3 greater hippocampus volume (p = 0.036). DHA = docosahexaenoic acid; EPA = eicosapentaenoic acid; RBC = red blood cell.

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