Neurology
Mixtures of key components of the external exposome in association with MRI biomarkers of brain structure: Multi-Ethnic Study of Atherosclerosis Cameron J. Reimer* Cameron Reimer Yorghos Tripodis Koichiro Shiba Peter James Kipruto Kirwa Susan R. Heckbert Jana Hirsch Lilah Besser Timothy M. Hughes Joel Kaufman M Maria Glymour Marcia Pescador Jimenez
Background: Environmental risk factor research in Alzheimer’s disease and related dementias (ADRD) has primarily focused on individual environmental exposures. However, it remains unknown how combinations of components of the ‘external exposome’ (i.e., environmental mixtures) are associated with cognitive health.
Methods: In the Multi-Ethnic Study of Atherosclerosis (MESA), we evaluated the associations between a mixture of environmental exposures and Magnetic Resonance Imaging (MRI) biomarkers of brain structure for 1,156 participants (mean age: 74.2 years) using Weighted Quantile Sum regression, adjusted for individual sociodemographic factors and MESA field center. We examined exposures including: outdoor air pollutants, street view-derived greenspace, neighborhood amenities, walkability, population density, and neighborhood socioeconomic status, and assigned exposures as cumulative averages based on residential address beginning at baseline (2000-2002). MRI biomarkers (assessed 2017-2021) included total: gray matter volume (GMV), white matter hyperintensity (WMH) volume, and fractional anisotropy (WM-FA).
Results: The environmental mixture was negatively associated with WM-FA (-0.0036, 95% CI: [-0.0054, -0.0018]). The negative association with gray matter volume (mL) was not statistically significant (-2.24, 95% CI: [-4.63, 0.15]). Higher mixture values indicate greater levels of potentially harmful exposures (e.g., increased air pollution, decreased greenspace). The observed mixture effect was largely driven by exposure to fine particulate matter for models of WM-FA, and both walkability and nitrogen dioxide for models of GMV. The environmental mixture was not associated with WMH volume.
Conclusion: The environmental mixture was associated with lower total GMV and WM-FA, measures of macrostructural and microstructural integrity, respectively. These models indicate that specific exposures may present higher risks to particular aspects of brain health.