title: Red blood cell ω-3 fatty acid levels and markers of accelerated brain aging.
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 = 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.
  
  
  CONCLUSIONS
  Lower RBC DHA levels are associated with smaller brain volumes and a "vascular" pattern of cognitive impairment even in persons free of clinical dementia.
authors.affiliation: Department of Medicine, Division of Geriatric Medicine, Easton Center for Alzheimer’s Disease Research, David Geffen School of Medicine at the University of California at Los Angeles, Los Angeles, USA. ztan@mednet.ucla.edu
authors.forename: Z S
authors.initials: ZS
authors.lastname: Tan
authors.forename: W S
authors.initials: WS
authors.lastname: Harris
authors.forename: A S
authors.initials: AS
authors.lastname: Beiser
authors.forename: R
authors.initials: R
authors.lastname: Au
authors.forename: J J
authors.initials: JJ
authors.lastname: Himali
authors.forename: S
authors.initials: S
authors.lastname: Debette
authors.forename: A
authors.initials: A
authors.lastname: Pikula
authors.forename: C
authors.initials: C
authors.lastname: Decarli
authors.forename: P A
authors.initials: PA
authors.lastname: Wolf
authors.forename: R S
authors.initials: RS
authors.lastname: Vasan
authors.forename: S J
authors.initials: SJ
authors.lastname: Robins
authors.forename: S
authors.initials: S
authors.lastname: Seshadri
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism* / Q000523:psychology; D000544:Alzheimer Disease / Q000378:metabolism / Q000523:psychology; D001921:Brain / Q000378:metabolism*; D003071:Cognition / Q000502:physiology; D003704:Dementia / Q000378:metabolism / Q000523:psychology; D004912:Erythrocytes / Q000378:metabolism*; D015525:Fatty Acids, Omega-3 / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D012307:Risk Factors
chemical_list: D015525:Fatty Acids, Omega-3