A – 95 Investigating the Mediating Role of Brain Volume in the Relationship Between Omega-3 Levels and Cognitive Performance in Healthy Older Adults

Abstract Objective We aim to investigate how omega-3 red cell blood count (RBC) correlates with cognitive performance and whether brain volume mediates this relationship. Method Forty participants drawn from the Adventist Health Study-2 Cognitive and Neuroimaging Substudy (M=76.25, SD=8.29; 48.9% female) completed cognitive testing from the Cogstate Brief Battery (CBB): One Back (ONB) and Two Back (TWOB). Brain volume was assessed using Freesurfer analysis of 3D T1-weighted MPRAGE sequences on a 3T Siemens MRI. Docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and an omega-3 index (sum of DHA and EPA) were measured from blood. Linear regression analyses, controlling for age and sex, examined the relationships between omega-3, brain volume, and CBB performance. Hayes Process Macro Mediation analysis assessed the potential mediating effect of brain volume on the relationship between omega-3 and cognitive performance. Results EPA, DHA, and the omega-3 index were significantly associated with ONB reaction time (β=-0.235, p=0.05; β=-0.285, p=0.02; β=-0.284, p=0.02), and accuracy (β=0.346, p=0.007; β=0.358, p=0.005; β=.378, p=.003), respectively. A negative relationship was found between DHA and TWOB reaction time (β=-0.217, p=0.05), but not TWOB accuracy. There were no significant indirect effects of omega-3 RBC on ONB or TWOB scores through brain volume. Conclusion Higher levels of omega-3s were associated with improved cognitive performance in tasks of working memory. Brain volume did not mediate these relationships, suggesting that the beneficial effects of omega-3s on cognitive function may operate through mechanisms independent of regional brain volume. These findings highlight the potential role of omega-3s in cognitive health in aging populations.