Background: The pathogenesis of dementia may be related to oxidative stress, and an early stage of Alzheimer's disease is oxidative neuronal damage. One strong antioxidant that has been shown to protect against neuronal damage is vitamin E. Some biologic and epidemiologic studies have suggested that antioxidant therapy could reduce neuronal damage if it is started before the onset of major cognitive decline and taken for a long duration. Clinical trials of patients with Alzheimer's disease or mild cognitive impairment and older patients with normal cognitive function have shown no benefit from antioxidant therapy. However, these studies lacked long-term follow-up. Kang and colleagues evaluated the long-term effect of vitamin E supplementation on cognitive function in women.

The Study: This randomized, double-blind, placebo-controlled trial of vitamin E supplementation was part of the Women's Health Study. Women were randomly assigned to receive 600 IU of vitamin E daily or placebo. The trial started in 1992; in 1998, a cognitive function subgroup was initiated with participants who were 65 years or older. Each year, all participants were sent a 12-month supply of medication or placebo and were asked to complete a questionnaire about compliance, adverse events, lifestyle characteristics, and clinical outcomes. In 1998, those in the subgroup had an initial cognitive function assessment over the telephone, which included five tests measuring general cognition, verbal memory, and category fluency. The assessment was repeated in 2000 and 2002. The main outcome was the global composite score on the five tests over time.

Results: At the end of the trial, the total study population was 5,845, and the mean follow-up time was 9.6 years. The vitamin E and placebo groups had similar characteristics except for a higher level of education in the placebo group. Cognitive function scores at the start of the study were similar for the placebo and treatment groups. There was no difference between the groups with regard to cognitive change over time.

Conclusions: Vitamin E supplementation does not offer cognitive benefits in healthy older women. Although the study did not address the use of vitamin E at younger ages, it showed that vitamin E supplementation of 10 years or less did not offer neuroprotection.