Effects of iron repletion on brain iron content, myelination, neural network activation, and cognition.
Authors
Affiliations (8)
Affiliations (8)
- Department of Pathology and Cell Biology, Columbia University College of Physicians and Surgeons - New York Presbyterian Hospital, New York, United States of America.
- Cognitive Neuroscience Division in Neurology, Columbia University College of Physicians and Surgeons - New York Presbyterian Hospital, New York, United States of America.
- Department of Radiology, Weill Cornell Medical College, New York, United States of America.
- New York Blood Center, New York, United States of America.
- Department of Neurology, Columbia University College of Physicians and Surgeons - New York Presbyterian Hospital, New York, United States of America.
- Department of Pediatrics, Columbia University College of Physicians and Surgeons - New York Presbyterian Hospital, New York, United States of America.
- Department of Radiology, Columbia University College of Physicians and Surgeons - New York Presbyterian Hospital, New York, United States of America.
- Department of Medicine, Columbia University College of Physicians and Surgeons - New York Presbyterian Hospital, New York, United States of America.
Abstract
Blood donation increases the risk of iron deficiency, but its impact on brain iron, myelination, and neurocognition remains unclear. 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. 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). 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. gov NCT02990559. NIH grants HL133049, HL139489, and UL1TR001873.