Association of Red Blood Cell Omega-3 Fatty Acids With MRI Markers and Cognitive Function in Midlife: The Framingham Heart Study.
Level 4 - case-series / case-control
Cross-sectional observational study evaluating associations at a single time point
PubMed 36198518 · doi:10.1212/WNL.0000000000201296
What was done
Researchers analyzed cross-sectional data from 2,183 dementia- and stroke-free participants (mean age 46 years, 53% women, 22% APOE-e4 carriers) from the Framingham Heart Study Third-Generation and Omni 2 cohorts. Red blood cell (RBC) concentrations of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) were measured using gas chromatography, and an Omega-3 index was calculated as EPA + DHA. Multivariable linear regression models evaluated associations of omega-3 levels with brain MRI measures (total brain, gray matter, hippocampal, and white matter hyperintensity volumes) and cognitive domain scores (episodic memory, processing speed, executive function, and abstract reasoning), adjusting for potential confounders and testing for interactions with APOE genotype.
What was found
Higher Omega-3 index was significantly associated with larger hippocampal volume (standard deviation unit beta ± standard error: 0.003 ± 0.001, p = 0.013) and higher abstract reasoning scores (0.17 ± 0.07, p = 0.013), with similar associations observed for DHA and EPA independently. In APOE-e4 noncarriers, higher DHA or Omega-3 index was associated with larger hippocampal volumes. In APOE-e4 carriers, higher EPA was related to better abstract reasoning, and higher levels across all omega-3 predictors were associated with lower white matter hyperintensity burden.
Why it matters
This study provides evidence that circulating omega-3 fatty acid levels correlate with favorable structural brain measures and cognitive performance as early as midlife, with patterns that may differ by APOE-e4 genetic risk.
Limits
The cross-sectional design precludes establishing causality or temporal order. Subgroup analyses by APOE status were exploratory, and results from this specific cohort may have limited generalizability or be subject to residual confounding.
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- supports A higher omega-3 index is dose-dependently associated with larger hippocampal brain volume in older adults.