Higher spontaneous production of interleukin 1 or tumor necrosis factor alpha by peripheral blood mononuclear cells may be a marker of future risk of Alzheimer disease (AD) in older individuals. These data strengthen the evidence for a pathophysiologic role of inflammation in the development of clinical AD.

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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 ...

In this large, population-based cohort, baseline and long-term average serum total cholesterol levels were not associated with the risk for incident AD.

Background: Clinical hypothyroidism and hyperthyroidism are recognized causes of reversible dementia, but previous studies relating thyrotropin levels to cognitive performance in clinically euthyroid persons have yielded inconsistent results. Methods:We related serum thyrotropin concentrations measured at baseline (March 1977-November 1979 to the risk of Alzheimer disease (AD) in 1864 cognitively intact, clinically euthyroid Framingham original cohort participants (mean age, 71 years; 59% women). Sex-specific Cox proportional hazards models were constructed using tertiles of thyrotropin concentration (tertile 2 as the referent) and adjusting for age, apolipoprotein E ε4 allele status, educational level, plasma homocysteine level, current smoking, body mass index, prevalent stroke, and atrial fibrillation.Results: During a mean follow-up of 12.7 years (range, 1-25 years), 209 participants (142 women) developed AD.Women in the lowest (Ͻ1.0 mIU/L) and highest (Ͼ2.1 mIU/L) tertiles of serum thyrotropin concentration were at increased risk for AD (multivariate-adjusted hazard ratio, 2.39 [95% confidence interval, 1.47-3.87] [PϽ.001] and 2.15 [95% confidence interval, 1.31-3.52] [P=.003], respectively) compared with those in the middle tertile. Thyrotropin levels were not related to AD risk in men. Analyses excluding individuals receiving thyroid supplementation did not significantly alter these relationships. In analyses limited to participants with serum thyrotropin levels of 0.1 to 10.0 mIU/L, the U-shaped relationship between thyrotropin level and AD risk was maintained in women but not when analyses were limited to those with thyrotropin levels of 0.5 to 5.0 mIU/L. Conclusion:Low and high thyrotropin levels were associated with an increased risk of incident AD in women but not in men.