Effects of iron repletion on brain iron content, myelination, neural network activation, and cognition.
Academic Article
Overview
abstract
BACKGROUND: Blood donation increases the risk of iron deficiency, but its impact on brain iron, myelination, and neurocognition remains unclear. METHODS: This ancillary study enrolled 67 iron-deficient blood donors, 19-73 years of age, participating in a double-blind, randomized trial. After donating blood, positive and negative susceptibility were measured using Quantitative Susceptibility Mapping (QSM) magnetic resonance imaging (MRI) to estimate brain iron and myelin levels, respectively. Furthermore, neurocognitive function was evaluated using the NIH Toolbox, and neural network activation patterns were assessed during neurocognitive tasks using functional MRI (fMRI). Donors were randomized to intravenous iron repletion (one-gram iron) or placebo, and outcome measures repeated approximately four months later. RESULTS: Iron repletion corrected systemic iron deficiency and led to trends toward increased whole brain iron (P=0.04) and myelination (P=0.02), with no change in the placebo group. Although overall cognitive performance did not differ significantly between groups, iron-treated participants showed improved engagement of functional neural networks (e.g., memory pattern activation during speed tasks, P<0.001). Brain region-specific changes in iron and myelin correlated with cognitive performance: iron in the putamen correlated with working memory scores (P<0.01), and thalamic myelination correlated with attention and inhibitory control (P<0.01). CONCLUSION: Iron repletion in iron-deficient blood donors may influence brain iron, myelination, and function, with region-specific changes in iron and myelination linked to distinct cognitive domains. CLINICALTRIALS: gov NCT02990559. FUNDING: NIH grants HL133049, HL139489, and UL1TR001873.
