Association of Red Blood Cell Omega-3 Fatty Acids With MRI Markers and Cognitive Function in Midlife
Claudia L. Satizábal, Jayandra J. Himali, Alexa Beiser, Ramachandran S. Vasan, Debora Melo van Lent, Dibya Himali, Hugo J. Aparicio, Pauline Maillard, Charles DeCarli, William S. Harris, Sudha Seshadri
Abstract
<h3>Background and Objectives</h3> Diet may be a key contributor to brain health in midlife. In particular, omega-3 fatty acids have been related to better neurologic outcomes in older adults. However, studies focusing on midlife are lacking. We investigated the cross-sectional association of red blood cell (RBC) omega-3 fatty acid concentrations with MRI and cognitive markers of brain aging in a community-based sample of predominantly middle-aged adults and further explore effect modification by <i>APOE</i> genotype. <h3>Methods</h3> We included participants from the Third-Generation and Omni 2 cohorts of the Framingham Heart Study attending their second examination. Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) concentrations were measured from RBC using gas chromatography, and the Omega-3 index was calculated as EPA + DHA. We used linear regression models to relate omega-3 fatty acid concentrations to brain MRI measures (i.e., total brain, total gray matter, hippocampal, and white matter hyperintensity volumes) and cognitive function (i.e., episodic memory, processing speed, executive function, and abstract reasoning) adjusting for potential confounders. We further tested for interactions between omega-3 fatty acid levels and <i>APOE</i> genotype (e4 carrier vs noncarrier) on MRI and cognitive outcomes. <h3>Results</h3> We included 2,183 dementia-free and stroke-free participants (mean age of 46 years, 53% women, 22% <i>APOE</i>-e4 carriers). In multivariable models, higher Omega-3 index was associated with larger hippocampal volumes (standard deviation unit beta ±standard error; 0.003 ± 0.001, <i>p</i> = 0.013) and better abstract reasoning (0.17 ± 0.07, <i>p</i> = 0.013). Similar results were obtained for DHA or EPA concentrations individually. Stratification by <i>APOE</i>-e4 status showed associations between higher DHA concentrations or Omega-3 index and larger hippocampal volumes in <i>APOE</i>-e4 noncarriers, whereas higher EPA concentrations were related to better abstract reasoning in <i>APOE</i>-e4 carriers. Finally, higher levels of all omega-3 predictors were related to lower white matter hyperintensity burden but only in <i>APOE</i>-e4 carriers. <h3>Discussion</h3> Our results, albeit exploratory, suggest that higher omega-3 fatty acid concentrations are related to better brain structure and cognitive function in a predominantly middle-aged cohort free of clinical dementia. These associations differed by <i>APOE</i> genotype, suggesting potentially different metabolic patterns by APOE status. Additional studies in middle-aged populations are warranted to confirm these findings.