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Omega-3 fatty acid concentrations in red blood cells were linked with brain structure and cognitive function in midlife, an exploratory cross-sectional study showed.

In about 2,200 people with an average age of 46, a higher omega-3 index was associated with a larger hippocampal volume and better abstract reasoning, according to Claudia Satizabal, PhD, of the University of Texas Health Science Center at San Antonio, and colleagues.

In addition, APOE4 carriers with a higher omega-3 index had a lower white matter hyperintensity burden, they reported in .

The omega-3 index combined docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) concentrations measured by gas chromatography.

The study is one of the first to identify relationships between omega-3 polyunsaturated fatty acids (PUFA), like DHA and EPA, and brain health in a younger population.

"The new contribution here is that, even at younger ages, if you have a diet that includes some omega-3 fatty acids, you are already protecting your brain for most of the indicators of brain aging that we see at middle age," Satizabal said in a statement.

Omega-3 fatty acids are obtained largely from dietary sources like cold-water, oily fish or omega-3 fortified foods, or through nutritional supplements. In the brain, DHA is incorporated into neuronal and glial cell membranes. Both DHA and EPA are metabolized into bioactive molecules involved in neurogenesis, neurotransmission, and inflammation resolution.

In older adults, observational studies have suggested that higher DHA and EPA intake may be disease. Omega-3 fatty acid levels also may protect older brains from environmental exposures like air pollution. Studies have linked pro-inflammatory diets, which are low in omega-3s, to brain volume and other markers of brain aging in older people.

"Despite the beneficial associations observed for brain outcomes in population-based and experimental studies, results from dietary intervention studies using omega-3 PUFA supplementation have been inconsistent," Satizabal and colleagues pointed out.

"These studies may be hampered in part by interventions that are deemed too late in the course of the disease, when individuals may have already experienced significant neuronal damage," they noted.

The researchers evaluated 2,183 predominantly middle-aged people in the Framingham Heart Study Third-Generation and Omni 2 cohorts who were dementia-free and stroke-free at baseline. Overall, 53% were women and 22% were APOE4 carriers.

Participants had brain MRI and cognitive function tests for episodic memory, processing speed, executive function, and abstract reasoning.

Higher levels of all omega-3 predictors -- EPA, DHA, and the omega-3 index -- were linked with larger hippocampal volumes when modeled continuously. Every standard deviation unit increase of log-transformed omega-3 index was related to 0.003 cm³ larger hippocampal volume relative to intracranial volume. Associations between higher omega-3 PUFA and larger hippocampal volumes remained significant after accounting for vascular risk factors.

All three omega-3 predictors were tied to better abstract reasoning test scores. Participants in the top three quartiles of EPA levels had better abstract reasoning performance than those in the bottom EPA quartile. Again, associations remained after adjusting for vascular risk factors.

Higher levels of all omega-3 predictors also were linked with reduced white matter hyperintensity volume in APOE4 carriers. Increasing EPA levels were tied to better performance in abstract reasoning tests in APOE4 carriers, but not in non-carriers.

The findings suggest that modest omega-3 consumption may be enough to preserve brain function, the researchers noted. "This is in line with the current dietary guidelines to consume at least two servings of fish per week to improve cardiovascular health," Satizabal said.

"These results need to be confirmed with additional research, but it's exciting that omega-3 levels could play a role in improving cognitive resilience, even in middle-aged people," she added.

Limitations include a largely white population in the study cohort and the cross-sectional design of the study, which provided only a snapshot in time, the researchers acknowledged.

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