Brain Iron Mediates the Relationship Between Cognition and Neighborhood Socioeconomic Status in Youth
Non-heme iron is a critical metabolic cofactor essential for healthy development. Iron deficiency is the most common nutritional disorder in the world, with greater prevalence of non-heme iron deficiency among individuals of lower socioeconomic status (SES). However, it remains unknown how brain iron accumulation during development may impact cognition. Brain iron can be measured in vivo using R2* weighted magnetic resonance imaging (MRI). Here, we used R2* MRI to quantify iron in the basal ganglia (BG) in a large sample of youth ages 8-23 imaged as part of the Philadelphia Neurodevelopmental Cohort (N=1,147, 54% female). Mean R2* signal within each bilateral BG region was modeled using generalized additive models with penalized splines to capture both linear and nonlinear developmental effects. As expected from prior reports, R2* increased in the BG throughout youth (all regions pfdr<0.001). Across all ages, lower R2* levels in the caudate (pfdr<0.02) was associated with diminished cognitive performance. Lower neighborhood SES was associated with both diminished cognition (p<0.001), as well as lower R2* in the caudate (pfdr=0.02). Critically, the relationship between cognition and SES was significantly mediated by caudate R2* (p=0.007). Taken together, these results suggest that brain iron is important for facilitating cognitive development in youth, and may provide a mechanism by which public health interventions focused on improving nutrition in low SES neighborhoods might aid cognitive development.
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