Red blood cell omega-3 status and longitudinal cognition in individuals at risk of Alzheimer's disease

Background: Many observational studies on dietary omega-3 fatty acids (FAs) and cognition focused on docosahexaenoic acid (DHA), because its significant role in brain. There is growing interest in whether other omega-3 FAs may also display cognitive benefits.

Objectives: To examine the associations between the blood levels of three different omega-3 FAs (DHA; eicosapentaenoic acid [EPA]; and alpha-linolenic acid [ALA]) and 3-year changes in cognitive performance in a cohort of cognitively unimpaired individuals at high risk of Alzheimer's disease (AD).

Methods: Prospective longitudinal study conducted in 323 participants from the ALFA (ALzheimer and FAmilies) Study. We determined the baseline levels of omega-3 FAs in red blood cells (RBCs) using gas-chromatography. Participants underwent a comprehensive neuropsychological battery at baseline and after 3 yrs. We studied cognitive outcomes as rate of change between visits. We first constructed multivariate models to examine the association between RBC-DHA and the preclinical Alzheimer's cognitive composite (PACC) score, also examining the effect of gender, APOE-ε4 carriership, and AD pathology (defined cerebrospinal fluid amyloid-beta and tau). As exploratory analysis, we examined associations between RBC-EPA and RBC-ALA with PACC, as well as those between omega-3 FAs and composite z-scores for attention, executive functioning, episodic memory, visual processing, and language domains.

Results: RBC-DHA was associated with a positive (improved) global cognition (PACC) rate of change (estimate = 0.011, 95% confidence interval [CI] = 0.001;0.021, P = 0.024). No statistically significant interactions were observed for sex, APOE-ε4 carriership, or AD pathology. Higher RBC-ALA status was associated with positive rate of change (better performing) in visual processing (estimate = 0.425, 95% CI = 0.168;0.682, P = 0.001).

Conclusions: In individuals at risk of AD, RBC-DHA and RBC-ALA showed positive associations with longitudinal cognition. These findings add to the observational evidence linking omega-3 FAs with improved brain health.