The diet may significantly impact brain health in midlife, especially omega-3 fatty acids, which have been linked to better neurological outcomes in older people. However, there have been few studies focusing on midlife. 

This study examined the cross-sectional relationship between red blood cell (RBC) Omega-3 fatty acid concentrations, brain MRI, and cognitive markers of brain aging in a community-based sample of predominantly middle-aged adults. In addition, it explored whether the APOE genotype affected the effect.

Previous studies have shown that dietary intake and circulating levels of EPA and DHA are associated with dementia risk, but the underlying mechanisms remain unclear. 

A team of researchers compared omega-3 levels in red blood cells from 2,183 dementia- and stroke-free participants for possible correlations with brain MRI and cognitive function measurements, adjusting for potential confounders.

The authors further explored whether omega-3 levels and APOE genotype could be correlated with cognitive outcomes on MRI since APOE genotypes determine whether you are at risk for Alzheimer’s disease.

This present study included participants from the Third-Generation and Omni 2 cohorts of the Framingham Heart Study who attended their second examination. The researchers used a gas chromatography method to measure the concentration of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) in RBC, and EPA + DHA was used to calculate an Omega-3 index. 

As a result of linear regression modeling, Omega-3 fatty acid concentrations were related to brain MRI measures (i.e., total brain, total gray matter, hippocampal hyperintensity volumes, and white matter hyperintensity volumes) and cognitive functions (i.e., episodic memory, processing speed, executive function, and abstract reasoning) after adjusting for possible confounders.

Results of the Study

Among 2,183 participants who were free of dementia and stroke (average age 46 years, 53% female, 22% APOE-e4), a higher Omega-3 index was associated with larger hippocampal volumes (standard deviation unit beta±standard error; 0.003 ±0.001, p=0.04), and better abstract reasoning (0.17 ±0.07, p=0.013).

Individual concentrations of DHA or EPA also showed similar results. APOE-e4 non-carriers were associated with a larger hippocampal volume with higher DHA concentrations or Omega-3 indexes, while APOE-e4 carriers had better abstract reasoning because of higher EPA concentrations. 

The presence of all Omega-3 predictors was associated with lower white matter hyperintensity burden only in APOE-e4 carriers.

Despite being exploratory, the results suggest that higher omega-3 fatty acids are associated with better brain structure and cognitive function in a predominantly middle-aged population free of clinical dementia. 

There was a significant difference in metabolic patterns based on the APOE genotype, suggesting that metabolic practices may differ based on the APOE genotype. However, further studies in middle-aged populations are needed to confirm these results.

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