Effects of n-3 fatty acids on cognitive decline: A randomized, double-blind, placebo-controlled trial in stable myocardial infarction patients

Background: Epidemiological studies suggest a protective effect of n-3 fatty acids derived from fish (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) against cognitive decline. For alpha-linolenic acid (ALA) obtained from vegetable sources, the effect on cognitive decline is unknown. We examined the effect of n-3 fatty acid supplementation on cognitive decline in coronary heart disease patients. Methods: The analysis included 2911 coronary patients (78% men) aged 60 to 80 years who participated in a double-blind placebo-controlled trial of n-3 fatty acids and cardiovascular diseases (Alpha Omega Trial). By using a 2 X 2 factorial design, patients were randomly assigned to margarines that provided 400 mg/d of EPA DHA, 2 g/d of ALA, both EPA DHA and ALA, or placebo for 40 months. Cognitive function was assessed by the Mini-Mental State Examination (MMSE) at baseline and after 40 months. The effect of n-3 fatty acids on change in MMSE score was assessed using analysis of variance. Logistic regression analysis was used to examine the effects on risk of cognitive decline, defined as a decrease of 3 or more points in MMSE score or incidence of dementia. Results: Patients in the active treatment groups had an additional intake of 384 mg of EPA DHA, 1.9 g of ALA, or both. The overall MMSE score in this cohort was 28.3 +/- 1.6 points, which decreased by 0.67 +/- 2.25 points during follow-up. Changes in MMSE score during intervention did not differ significantly between EPA DHA and placebo (-0.65 vs -0.65 points, P = .44) or between ALA and placebo (-0.60 vs -0.74 points, P = .12). The risk of cognitive decline was 1.03 (95% confidence interval: 0.84-1.26, P = .80) for EPA DHA (vs placebo) and 0.90 (0.74-1.10, P = .31) for ALA (vs placebo). Conclusion: This large intervention study showed no effect of dietary doses of n-3 fatty acids on global cognitive decline in coronary heart disease patients. (C) 2012 The Alzheimer's Association. All rights reserved.