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

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 is an element of 4 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: beta +/- 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 omega-3 index (RBC DHA + EPA) levels (Q1 vs Q2-4) also had lower scores on tests of visual memory (beta +/- SE = -0.47 +/- 0.18; p = 0.008), executive function (beta +/- SE = -0.07 +/- 0.03; p = 0.004), and abstract thinking (beta +/- 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. Neurology (R) 2012;78:658-664