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

Many observational studies on dietary ω-3 (n-3) fatty acids (FAs) and cognition have focused on DHA, because of its significant role in brain. There is growing interest in whether other ω-3 FAs may also display cognitive benefits.

This study examined the associations between the blood concentrations of 3 different ω-3 FAs [DHA; 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 disease (AD).

Prospective longitudinal study conducted in 323 participants from the ALFA (Alzheimer and Families) Study. We determined the baseline concentrations of ω-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 cognitive composite (PACC) score, also examining the effect of gender, APOE-ε4 carriership, and AD pathology (defined cerebrospinal fluid amyloid-β and τ). As exploratory analysis, we examined associations between RBC EPA and RBC ALA with PACC, as well as those between ω-3 FAs and composite z-scores for attention, executive functioning, episodic memory, visual processing, and language domains.

RBC DHA was associated with a positive (improved) global cognition (PACC) rate of change (estimate: 0.011; 95% 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).

In individuals at risk of AD, RBC DHA and RBC ALA show positive associations with longitudinal cognition. These findings add to the observational evidence linking ω-3 FAs with improved brain health. This trial was registered at clinicaltrials.gov as NCT02485730 (https://clinicaltrials.gov/study/NCT02485730).