Essential Fatty Acid Deficiency as a modifiable determinant of cognitive dysfunction among 6-18-year-old Ugandan children of varying perinatal HIV status

 This longitudinal investigation examined baseline serum fatty acid concentrations and their relationships with executive function over 12 months in adolescents from Kampala, Uganda, stratified by perinatal HIV status. The cohort included three groups: adolescents with perinatal HIV infection (APHIV; n = 122), adolescents perinatally exposed but uninfected (AHEU; n = 130), and adolescents perinatally unexposed and uninfected (AHUU; n = 123). Baseline serum fatty acids were measured and categorized into tertiles. Executive function was assessed using both questionnaire-based self-report measures and performance-based tests, with outcomes analyzed as z-scores at baseline, 6 months, and 12 months. Linear mixed-effects models were used to relate baseline fatty acid tertiles to repeated executive function measures across the follow-up period, and mean differences with 95% confidence intervals are reported for the principal associations.

The study centered on polyunsaturated fatty acids (PUFAs), particularly omega-3 (ω-3) PUFAs and their components, and on saturated fatty acids (SFAs), testing the hypotheses that higher PUFA concentrations would be associated with improved executive function while higher SFA concentrations would be associated with worse executive function, especially among adolescents affected by perinatal HIV exposure or infection. Across the full sample of adolescents, moderate compared with low ω-3 PUFA concentrations were associated with reductions in self-reported executive dysfunction. Specifically, the total ω-3 PUFA measure, the Omega-3 Index, the highly unsaturated fatty acid ratio, and DHA each showed mean differences indicative of less reported executive dysfunction for moderate versus low concentrations (total ω-3 PUFA—MD: −0.51; 95% CI: −0.87, −0.15; Omega-3 Index—MD: −0.52; 95% CI: −0.88, −0.16; highly unsaturated fatty acid ratio—MD: −0.42; 95% CI: −0.79, −0.06; DHA—MD: −0.58; 95% CI: −0.94, −0.21).

When analyses focused on adolescents with perinatal HIV infection (APHIV), different patterns emerged. High concentrations of EPA were associated with increased self-reported executive dysfunction (MD: 1.07; 95% CI: 0.27, 1.87). Select saturated fatty acids — arachidic acid, behenic acid, and lignoceric acid — were associated with increased executive dysfunction on performance-based measures among APHIV (arachidic acid—MD: 0.86; 95% CI: 0.38, 1.34; behenic acid—MD: 0.76; 95% CI: 0.23, 1.29; lignoceric acid—MD: 0.78; 95% CI: 0.24, 1.31). 

The researchers concluded that higher ω-3 PUFA concentrations relate to better questionnaire-based executive function across adolescents, whereas among APHIV, high EPA and certain SFAs relate to worse executive function. The findings underscore potential roles for ω-3 PUFAs in supporting executive function in vulnerable populations and point to the need for further research into fatty acid–executive function relationships among adolescents affected by perinatal HIV.