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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 middleaged to elderly community-based cohort. Methods:We related RBC DHA and EPA levels in dementia-free Framingham Study participants (n ϭ 1,575; 854 women, age 67 Ϯ 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 ⑀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: ␤ Ϯ SE ϭ Ϫ0.49 Ϯ 0.19; p ϭ 0.009, and 0.12 Ϯ 0.06; p ϭ 0.049, respectively) with persistence of the association with total brain volume in multivariable analyses. Participants with lower DHA and -3 index (RBC DHAϩEPA) levels (Q1 vs Q2-4) also had lower scores on tests of visual memory (␤ Ϯ SE ϭ Ϫ0.47 Ϯ 0.18; p ϭ 0.008), executive function (␤ Ϯ SE ϭ Ϫ0.07 Ϯ 0.03; p ϭ 0.004), and abstract thinking (␤ Ϯ SE ϭ Ϫ0.52 Ϯ 0.18; p ϭ 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 ® 2012;78:658-664 GLOSSARY AD ϭ Alzheimer disease; BMI ϭ body mass index; DHA ϭ docosahexaenoic acid; DM ϭ diabetes mellitus; EPA ϭ eicosapentaenoic acid; LM-d ϭ delayed recall components of the Logical Memory test; NP ϭ neuropsychological; PAI ϭ physical activity index; PUFA ϭ polyunsaturated fatty acid; RBC ϭ red blood cell; SBP ϭ systolic blood pressure; SCI ϭ silent cerebral infarct; SIM ϭ Similarities test; TCBV ϭ total cerebral brain volume; THV ϭ temporal horn volume; VR-d ϭ delayed recall component of the Visual Reproductions test; WMHV ϭ white matter hyperintensity volume.Higher fish intake has been associated with a reduced risk of cardiovascular mortality 1,2 and stroke.3 While several large epidemiologic studies 4,5 have shown an association between the estimated intake of fatty fish and a lower risk for dementia, some other investigations have failed to confirm such a protective association. 6 One possible reason for these inconsistent results is the limited ability of dietary recall surveys and food frequency questionnaires to quantify blood levels of fatty acids. 7,8 In the Framingham original cohort, participants in the top quartile of plasma phosphatidylcholine docosahexaenoic acid (DHA) levels had 37% and 47% lower risks of Alzheimer disease (AD) and all-cause dementia, respectively.9 Red blood ...

Background Age-adjusted stroke incidence has decreased over the past 50 years, likely due to changes in the prevalence and impact of various stroke risk factors. An updated version of the Framingham Stroke Risk Profile (FSRP) might better predict current risks in the Framingham Heart Study (FHS) and other cohorts. We compared the accuracy of the standard (Old), and of a revised (New) version of the FSRP in predicting the risk of all-stroke and ischemic stroke, and validated this new FSRP in two external cohorts, the 3 Cities (3C) and REGARDS studies. Methods We computed the old FSRP as originally described, and a new model that used the most recent epoch-specific risk factors' prevalence and hazard-ratios for persons ≥ 55 years and for the subsample ≥ 65 years (to match the age range in REGARDS and 3C studies respectively), and compared the efficacy of these models in predicting 5- and 10-year stroke risks. Results The new FSRP was a better predictor of current stroke risks in all three samples than the old FSRP (Calibration chi-squares of new/old FSRP: in men 64.0/12.1, 59.4/30.6 and 20.7/12.5; in women 42.5/4.1, 115.4/90.3 and 9.8/6.5 in FHS, REGARDS and 3C, respectively). In the REGARDS, the new FSRP was a better predictor among whites compared to blacks. Conclusions A more contemporaneous, new FSRP better predicts current risks in 3 large community samples and could serve as the basis for examining geographic and racial differences in stroke risk and the incremental diagnostic utility of novel stroke risk factors.