Erythrocyte omega-3 index, ambient fine particle exposure, and brain aging

Abstract

Objective: To examine whether long-chain omega-3 polyunsaturated fatty acid (LCn3PUFA) levels modify the potential neurotoxic effects of particle matter with diameters <2.5 µm (PM_2.5) exposure on normal-appearing brain volumes among dementia-free elderly women.

Methods: A total of 1,315 women (age 65-80 years) free of dementia were enrolled in an observational study between 1996 and 1999 and underwent structural brain MRI in 2005 to 2006. According to prospectively collected and geocoded participant addresses, we used a spatiotemporal model to estimate the 3-year average PM_2.5 exposure before the MRI. We examined the joint associations of baseline LCn3PUFAs in red blood cells (RBCs) and PM_2.5 exposure with brain volumes in generalized linear models.

Results: After adjustment for potential confounders, participants with higher levels of RBC LCn3PUFA had significantly greater volumes of white matter and hippocampus. For each interquartile increment (2.02%) in omega-3 index, the average volume was 5.03 cm³ (p < 0.01) greater in the white matter and 0.08 cm³ (p = 0.03) greater in the hippocampus. The associations with RBC docosahexaenoic acid and eicosapentaenoic acid levels were similar. Higher LCn3PUFA attenuated the inverse associations between PM_2.5 exposure and white matter volumes in the total brain and multimodal association areas (frontal, parietal, and temporal; all p for interaction <0.05), while the associations with other brain regions were not modified. Consistent results were found for dietary intakes of LCn3PUFAs and nonfried fish.

Conclusions: Findings from this prospective cohort study among elderly women suggest that the benefits of LCn3PUFAs on brain aging may include the protection against potential adverse effects of air pollution on white matter volumes.

Figure 1. Associations between PM_2.5 exposure and brain normal-appearing WMVs stratified by RBC omega-3 index

All models (A–C) were constructed by using linear regression model with adjustment for intracranial volume, age, race/ethnicity, US regions, education attainment, family income, employment, smoking status, alcohol consumption, body mass index, moderate or strenuous activity ≥20 min/d, prior depression, random assignment to hormone therapy, and medical histories (hypertension, diabetes mellitus, hypercholesterolemia, and cardiovascular diseases). Associations are expressed as the linear regression coefficients per interquartile (3.22 μg/m³) increment in the continuous variable of 3-year moving average particle matter with diameters <2.5 µm (PM_2.5) exposure before the MRI examination. For example, in panel A, for each interquartile increase in PM_2.5 exposure, the average white matter volume (WMV) was 11.52 cm³ smaller among participants with lower omega-3 index (less than median level) and 0.12 cm³ smaller among participants with higher omega-3 index (median level or greater). DHA = docosahexaenoic acid; EPA = eicosapentaenoic acid; RBC = red blood cell. Significance of p values: *p < 0.05, **p < 0.001, ***p < 0.0001.

Figure 2. Associations between PM_2.5 exposure and brain normal-appearing WMVs stratified by intakes of LCn3PUFAs and nonfried fish

All models (A–D) were constructed using linear regression models with the adjustment for intracranial volume, age, race/ethnicity, US regions, education attainment, family income, employment, smoking status, alcohol consumption, body mass index, moderate or strenuous activity ≥20 min/d, prior depression, random assignment to hormone therapy, and medical histories (hypertension, diabetes mellitus, hypercholesterolemia, and cardiovascular diseases). Associations are expressed as the linear regression coefficients per interquartile (3.22 μg/m³) increment in the continuous variable of particle matter with diameters <2.5 µm (PM_2.5) exposure before the MRI examination. For example, in panel A, for each interquartile increase in PM_2.5 exposure, the average white matter volume (WMV) was 11.92 cm³ smaller among participants with lower long chain omega-3 polyunsaturated fatty acid (LCn3PUFA) intake (less than median level) and 0.59 cm³ greater among participants with higher LCn3PUFA intake (median level or greater). DHA = docosahexaenoic acid; EPA = eicosapentaenoic acid. Significance of p values (main and interaction): *p < 0.05, **p < 0.001, ***p < 0.0001.