Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Sep 27:S0022-3166(25)00576-0.
doi: 10.1016/j.tjnut.2025.09.032. Online ahead of print.

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

Iolanda Lázaro  1 , Anna Brugulat-Serrat  2 , Marc Suárez-Calvet  3 , Karine Fauria  4 , Carolina Minguillon  5 , Juan-Domingo Gispert  6 , José Luis Molinuevo  7 , William S Harris  8 , Gonzalo Sánchez-Benavides  5 , Oriol Grau-Rivera  9 , Aleix Sala-Vila  10 ; ALFA study
Collaborators, Affiliations
Free article

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

Iolanda Lázaro et al. J Nutr. .
Free article

Abstract

Background: 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.

Objectives: 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).

Methods: 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.

Results: 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).

Conclusions: 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).

Keywords: biomarkers; diet; fatty acids; lifestyle; nutrition.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest MS-C has made presentations in symposia funded by Roche Diagnostics, S.L.U, Amirall, and Roche Farma, S.A; has also been a consultant and advisory board member for Grifols S.L. and Roche Diagnostics International; has received a research grant from Roche Diagnostics International, where payments were made to his institution (BBRC); and has received in-kind research support from Roche Diagnostics International, Avid Radiopharmaceuticals, Inc, Eli Lilly, and Janssen Research & Development. JLM is now employed full-time by H. Lundbeck A/S and earlier has provided consulting services or has served on advisory boards for a number of for-profit companies, and has given lectures at symposia supported by them, including Roche Diagnostics, Genentech, Novartis, Lundbeck, Oryzon, Biogen, Lilly, Janssen, Green Valley, MSD, Eisai, Alector, BioCross, GE Healthcare, and ProMIS Neurosciences. J-DG is currently a full-time employee of AstraZeneca; has received research funding from Roche Diagnostics, Hoffmann-La Roche, Life-MI, and GE Healthcare, along with consulting and/or speaker fees from Roche Diagnostics, Biogen, Philips Netherlands, Esteve, and Life-MI; has also served on the Molecular Neuroimaging Advisory Board of Prothena Neurosciences; and is a founder, shareholder, and member of the Board of Directors of Betascreen SL. WSH holds stock in OmegaQuant Analytics, LLC. AS-V has received research grant funding through his institution and support for attending professional meetings from the California Walnut Commission. The remaining authors declare no conflicts of interest.

Associated data

LinkOut - more resources