Background: Dietary n-3 polyunsaturated fatty acids improve brain functioning in animal studies, but there is limited study of whether this type of fat protects against Alzheimer disease.

Objective: To examine whether fish consumption and intake of different types of n-3 fatty acids protect against Alzheimer disease.

Design: Prospective study conducted from 1993 through 2000, of a stratified random sample from a geographically defined community. Participants were followed up for an average of 3.9 years for the development of Alzheimer disease.

Patients: A total of 815 residents, aged 65 to 94 years, who were initially unaffected by Alzheimer disease and completed a dietary questionnaire on average 2.3 years before clinical evaluation of incident disease.

Main Outcome Measure: Incident Alzheimer disease diagnosed in a structured neurologic examination by means of standardized criteria.

Results: A total of 131 sample participants developed Alzheimer disease. Participants who consumed fish once per week or more had 60% less risk of Alzheimer disease compared with those who rarely or never ate fish (relative risk, 0.4; 95% confidence interval, 0.2-0.9) in a model adjusted for age and other risk factors. Total intake of n-3 polyunsaturated fatty acids was associated with reduced risk of Alzheimer disease, as was intake of docosahexaenoic acid (22:6n-3). Eicosapentaenoic acid (20:5n-3) was not associated with Alzheimer disease. The associations remained unchanged with additional adjustment for intakes of other dietary fats and of vitamin E and for cardiovascular conditions.

Conclusion: Dietary intake of n-3 fatty acids and weekly consumption of fish may reduce the risk of incident Alzheimer disease.