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BACKGROUND: Oxidative stress mayplay a key role in the development of cognitive impairment. Long-termsupplementation with vitamin E, a strong antioxidant, may provide cognitivebenefits. METHODS: The Women's Health Study is a randomized, double-blind,placebo-controlled trial of vitamin E supplementation (600 IU [alpha-tocopherolacetate], on alternate days) begun between 1992 and 1995 among 39 876 healthy US women. From1998, 6377 women 65 years or older participated in a cognitive substudy. Threecognitive assessments of general cognition, verbal memory, and category fluencywere administered by telephone at 2-year intervals. The primary outcome was aglobal composite score averaging performance on all tests. Repeated measuresanalyses were conducted to examine mean performance and mean differences incognitive change, and logistic regression was used to estimate relative risksof substantial decline. RESULTS: There were no differences in global scorebetween the vitamin E and placebo groups at the first assessment (5.6 years afterrandomization: mean difference, -0.01; 95% confidence interval [CI], -0.04 to0.03) or at the last assessment (9.6 years of treatment: mean difference, 0.00;95% CI, -0.04 to 0.04). Mean cognitive change over time was also similar in thevitamin E group compared with the placebo group for the global score (meandifference in change, 0.02; 95% CI, -0.01 to 0.05; P = .16). The relative riskof substantial decline in the global score in the vitamin E group compared withthe placebo group was 0.92 (95% CI, 0.77 to 1.10). CONCLUSION: Long-term use ofvitamin E supplements did not provide cognitive benefits among generallyhealthy older women.Leggil'articolo