Is a randomized trial of antioxidants in the primary prevention of Alzheimer disease warranted?

Alzheimer disease is a common condition that severely affects both persons with the illness and their families. Prevention of Alzheimer disease is an urgent priority, but study of potentially modifiable risk factors for the illness is at an early stage. Laboratory studies suggest that oxidative mechanisms may be involved in the pathogenesis of Alzheimer disease and raise the possibility that antioxidant nutrients could be used in disease prevention. Observational studies suggest that antioxidant nutrients may have protective effects against a number of other common chronic diseases, including cardiovascular disease and cancer. Because the protective effects, if any, of antioxidant nutrients are likely to be small to moderate in magnitude, large-scale randomized trials of primary prevention will likely be necessary to resolve this issue, and a major question is how quickly to progress to expensive and time consuming trials needed to provide more definitive evidence. This is a difficult question, but the severity of the disease, the current absence of preventive strategies and the likelihood that observational studies alone will not provide clear resolution of the issue all suggest that it may be prudent to strongly consider such trials in the near future.