Limited information exists on the influence of docosapentaenoic acid (DPA) on cognitive function. We investigated the association between serum n-3 and n-6 DPAs and cognitive performance in an elderly population from the National Health and Nutrition Examination Survey, 2011–2014. Restricted cubic spline and logistic regression analyses were utilized. A total of 1,366 older participants were included. Elevated proportions of DPA(n3) in total serum fatty acids were slightly associated with higher DSST scores (OR 0.61, 95% CI (0.38–0.97)), and higher proportions of DPA(n6) in total serum fatty acids were significantly associated with lower scores on different cognitive tests (CERAD (1.64, 1.02-2.65), AFT (2.31, 1.43- 3.75), DSST (3.21, 1.98-5.22) and global cognition (2.85, 1.74–4.66)). After multivariable adjustment, DPA(n3) exhibited no association with cognitive performance, whereas DPA(n6) remained correlated with AFT (1.98, 1.13–3.48), DSST (2.63, 1.43–4.82) and global cognition (2.15, 1.19–3.90). In stratified analyses, higher levels of DPA(n3) were associated with better performance in CERAD among participants aged ≥70, in DSST among those without diabetes and in global cognition among people with lower incomes. Increased DPA(n6) levels were associated with worse performance in AFT and DSST among those aged 60–70 and in all cognitive tests among those with better incomes. In conclusions, elevated levels of serum DPA(n3) may be beneficial for cognitive performance among elderly adults, especially in those over 70 years, with lower incomes and without diabetes. Serum n-6 DPA might be negatively associated with cognitive function, and this association is more pronounced among those who aged 60–70 with higher incomes.
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