A longitudinal study of baseline fatty acid levels and executive function over 12 months among adolescents with and without perinatal HIV exposure or infection from Kampala, Uganda.

Background: Adolescence is critical for executive function development, and fatty acids, vital for brain development, may influence this process. This influence is understudied in populations affected by HIV, where malnutrition and neuroinflammation persist.

Objective: To determine associations between serum fatty acid levels and executive function in Ugandan adolescents over 12 months and evaluate modification by perinatal HIV status. It was hypothesized that PUFA levels associated with improved executive function, while SFA levels associated with worse executive function, especially in adolescents affected by perinatal HIV exposure/infection.

Methods: Adolescents with perinatal HIV infection (APHIV, n=122), adolescents HIV exposed uninfected (AHEU, n=130), and adolescents HIV unexposed uninfected (AHUU, n=123) were analyzed. Serum fatty acid levels were measured at baseline. Questionnaire- and performance-based measures of executive function (analyzed as z-scores) were assessed at baseline, 6-, and 12-months. Linear mixed-effects models were used to analyze associations between baseline serum fatty acid tertiles and repeated executive function measures. Mean differences (MDs) and their 95% confidence intervals (CIs) are reported.

Results: Among all adolescents, moderate v. low ω-3 PUFA levels associated with decreases in self-report executive dysfunction (MD (95% CI) total ω-3 PUFA: -0.51 (-0.87, -0.15); Omega-3 Index: -0.52 (-0.88, -0.16); highly unsaturated fatty acid (HUFA) ratio: -0.42 (-0.79, -0.06); DHA: -0.58 (-0.94, -0.21)). Among APHIV, high EPA (1.07 (0.27, 1.87)) and select SFA levels (arachidic acid: 0.86 (0.38, 1.34); behenic acid: 0.76 (0.23, 1.29); lignoceric acid: 0.78 (0.24, 1.31)) correlated with increased self-report and performance-based executive dysfunction, respectively.

Conclusions: Overall, higher ω-3 PUFA levels associated with better questionnaire-based executive function, but high EPA and SFA levels associated with worse executive function among APHIV. These findings support the potential of ω-3 PUFAs to improve executive function in vulnerable populations and highlight the importance of further studying the relationship between fatty acids and executive function among APHIV.