Carrying the APOE ɛ4 allele is the strongest genetic risk factor for developing late-onset Alzheimer’s disease. Animal studies suggest that early and high dose docosahexaenoic acid (DHA, an omega-3) can prevent cognitive decline. The goal of this project is to identify whether supplementation with high doses of DHA (2 grams per day) can slow cognitive decline in carriers of the APOE ɛ4 allele when started before the onset of cognitive impairment. We therefore propose a randomized clinical trial of DHA vs. placebo over two years in 320 adults without cognitive impairment but at risk for cognitive decline, stratified by APOE ɛ4 genotype.  Given the large risk associated with this genotype, the potential public health impact of a safe and inexpensive supplementation could have wide-spread applicability, especially in terms of reduced AD incidence.