SAN FRANCISCO—Treatment with antioxidants has no effect on cognition in older adults with eye disease, investigators reported at the 128th Annual Meeting of the American Neurological Association. The results, from an NIH-sponsored trial, showed that the use of antioxidants with or without copper and zinc for an average of seven years did not result in better or worse cognition compared with placebo in older adults with macular degeneration.

“While several observational studies have found that antioxidant use is associated with protection against cognitive decline and dementia, none of the trials has been randomized,” said the trial’s principal investigator, Kristine Yaffe, MD, Associate Professor of Psychiatry, Neurology, and Epidemiology at the University of California at San Francisco and the San Francisco Veterans Administration Hospital. “Other studies have suggested that zinc or copper supplementation may actually increase the risk of Alzheimer’s disease.”

VITAMINES, MINERALS, AND COGNITION

Dr. Yaffe’s present study included adults enrolled in the 11-center Age-Related Eye Disease Study, a macular degeneration trial. Participants were randomized to one of four daily treatments: antioxidants (500 mg of vitamin C, 400 IU of vitamin E, and 15 mg of ß-carotene); zinc (80 mg of zinc oxide) and copper (2 mg of cupric oxide); antioxidants plus zinc/copper; or placebo.

After a median of 6.9 years of treatment, 2,166 participants underwent six standard neuropsychological tests that measured performance on several cognitive domains. The tests included the immediate recall and delayed recall components of Logical Memory, Modified Mini-Mental State Examination (MMSE), Letter Fluency, Animal Categories, the immediate recall and word list mean components of the Buschke Memory Test, and Digits Backwards.

The mean age of the study population was 75. The four treatment groups were similar with respect to baseline demographic and clinical characteristics (current smoking; history of hypertension, diabetes, coronary atherosclerotic disease, or depression; use of antihypertensive drugs, cholesterol-lowering drugs, nonsteroidal anti-inflammatory drugs; nutritional intake; and age at randomization) and the mean cognitive scores associated with age, education, and race.

After controlling for age, sex, race, education, length of supplementation, and depression, the mean cognitive scores remained similar among treatment groups, Dr. Yaffe said. There was a nonsignificant reduction in the likelihood of cognitive impairment (a score of less than 80 on the MMSE) among participants randomized to zinc. There was no association between antioxidant treatment and cognitive impairment.

NO C AND E

Dr. Yaffe emphasized that any interpretation of the results must take into account limitations of the trial. “For example, because the study was limited to a cross-sectional comparison, it was not possible to determine whether treatments influence the rate of cognitive decline,” she said. Also, the participants who did not undergo cognitive testing tended to be older and less educated. “If they had participated, there may be a greater proportion satisfying the criteria for cognitive impairment,” she suggested. An additional limitation is that all participants had some degree of eye disease, and the study did not assess visuospatial skills.

“The message is that, at least in our hands, the 400 IU dose of vitamin E and 500 mg of vitamin C did not seem to improve cognitive function in our non–Alzheimer’s disease study population,” Dr. Yaffe said. As for further research in this area, Dr. Yaffe reported that an NIH-funded study that will be launched next year will seek to determine whether antioxidants prevent Alzheimer’s disease.

NR

—Jill Stein

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