Background—Cardiovascular factors are associated with cognitive decline. Antioxidants may be beneficial.

Methods and Results—The Women's Antioxidant Cardiovascular Study was a trial of vitamin E (402 mg every other day), beta carotene (50 mg every other day), and vitamin C (500 mg daily) for the secondary prevention of cardiovascular disease. From 1995 to 1996, women 40 years of age with cardiovascular disease or 3 coronary risk factors were randomized. From 1998 to 1999, a cognitive function substudy was initiated among 2824 participants 65 years of age. With 5 cognitive tests, cognition was assessed by telephone 4 times over 5.4 years. The primary outcome was a global composite score averaging all scores; repeated-measures analyses were used to examine cognitive change over time. Vitamin E supplementation and beta carotene supplementation were not associated with slower rates of cognitive change (mean difference in change for vitamin E versus placebo, -0.01; 95% confidence interval, -0.05 to 0.04; P=0.78; for beta carotene, 0.03; 95% confidence interval, -0.02 to 0.07; P=0.28). Although vitamin C supplementation was associated with better performance at the last assessment (mean difference, 0.13; 95% confidence interval, 0.06 to 0.20; P=0.0005), it was not associated with cognitive change over time (mean difference in change, 0.02; 95% confidence interval, -0.03 to 0.07; P=0.39). Vitamin C was more protective against cognitive change among those with new cardiovascular events during the trial (P for interaction=0.009).

Conclusions—Antioxidant supplementation did not slow cognitive change among women with preexisting cardiovascular disease or cardiovascular disease risk factors. A possible late effect of vitamin C or beta carotene among those with low dietary intake on cognition warrants further study.