BACKGROUND: Very-long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) are suggested to be related to cognitive performance in older adults. However, limited data exist on the association between n-3 PUFAs and performance in specific cognitive domains. OBJECTIVE: We evaluated the association between plasma n-3 PUFA proportions and cognitive performance in 5 cognitive domains and determined whether plasma n-3 PUFA proportions predict cognitive change over 3 y. DESIGN: We used data from the FACIT trial, in which participants received folic acid or placebo capsules for 3 y. Fatty acid proportions in plasma cholesteryl esters at baseline were measured in 807 men and women aged 50-70 y. Cognitive performance for memory, sensorimotor speed, complex speed, information-processing speed, and word fluency was assessed at baseline and after 3 y. The cross-sectional analyses were based on all 807 participants; the longitudinal analyses were based only on 404 participants in the placebo group. RESULTS: Higher plasma n-3 PUFA proportions predicted less decline in sensorimotor speed (multiple linear regression coefficient, z score = 0.31; 95% CI: 0.06, 0.57) and complex speed (0.40; 95% CI: 0.10, 0.70) over 3 y. Plasma n-3 PUFA proportions did not predict 3-y changes in memory, information-processing speed, or word fluency. The cross-sectional analyses showed no association between plasma n-3 PUFA proportions and performance in any of the 5 cognitive domains. CONCLUSIONS: In this population, plasma n-3 PUFA proportions were associated with less decline in the speed-related cognitive domains over 3 y. These results need to be confirmed in randomized controlled trials.