Peter P. Zandi, PhD; James C. Anthony, PhD; Ara S. Khachaturian, PhD; Stephanie V. Stone, PhD; Deborah Gustafson, PhD; JoAnn T. Tschanz, PhD; Maria C. Norton, PhD; Kathleen A. Welsh-Bohmer, PhD; John C. S. Breitner, MD; for the Cache County Study Group Arch Neurol.2004;61:82-88.

Background Antioxidants may protect the aging brain against oxidative damage associated with pathological changes of Alzheimer disease (AD).

Objective To examine the relationship between antioxidant supplement use and risk of AD.

Design Cross-sectional and prospective study of dementia. Elderly (65 years or older) county residents were assessed in 1995 to 1997 for prevalent dementia and AD, and again in 1998 to 2000 for incident illness. Supplement use was ascertained at the first contact.

Setting Cache County, Utah.

Participants Among 4740 respondents (93%) with data sufficient to determine cognitive status at the initial assessment, we identified 200 prevalent cases of AD. Among 3227 survivors at risk, we identified 104 incident AD cases at follow-up.

Main Outcome Measure Diagnosis of AD by means of multistage assessment procedures.

Results Analyses of prevalent and incident AD yielded similar results. Use of vitamin E and C (ascorbic acid) supplements in combination was associated with reduced AD prevalence (adjusted odds ratio, 0.22; 95% confidence interval, 0.05-0.60) and incidence (adjusted hazard ratio, 0.36; 95% confidence interval, 0.09-0.99). A trend toward lower AD risk was also evident in users of vitamin E and multivitamins containing vitamin C, but we saw no evidence of a protective effect with use of vitamin E or vitamin C supplements alone, with multivitamins alone, or with vitamin B–complex supplements.

Conclusions Use of vitamin E and vitamin C supplements in combination is associated with reduced prevalence and incidence of AD. Antioxidant supplements merit further study as agents for the primary prevention of AD. From the Department of Mental Health, Bloomberg School of Public Health (Drs Zandi, Anthony, and Khachaturian), and Advanced Academic Programs: Developmental Psychology (Dr Stone), The Johns Hopkins University, Baltimore, Md; Departments of Nutrition and Food Sciences (Dr Gustafson), Psychology (Drs Tschanz and Norton), and Family, Consumer, and Human Development (Dr Norton), and the Center for Epidemiologic Studies (Drs Tschanz and Norton), Utah State University, Logan; Department of Psychiatry and Behavioral Reduced Risk of Alzheimer Disease in Users of Antioxidant Vitamin Supplements

Sciences and the Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC (Dr Welsh-Bohmer); and Veterans Affairs Puget Sound Health Care System and Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle (Dr Breitner).