Abstract
BACKGROUND Blood donation increases the risk of iron deficiency, but its effect 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) 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 i.v. iron repletion (1 g iron) or placebo, and outcome measures repeated approximately 4 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.REGISTRATION ClinicalTrials.gov NCT02990559FUNDING This work was funded by the NIH.
Authors
Eldad A. Hod, Christian Habeck, Hangwei Zhuang, Alexey Dimov, Pascal Spincemaille, Debra Kessler, Zachary C. Bitan, Yona Feit, Daysha Fliginger, Elizabeth F. Stone, David Roh, Lisa Eisler, Stephen Dashnaw, Elise Caccappolo, Donald J. McMahon, Yaakov Stern, Yi Wang, Steven L. Spitalnik, Gary M. Brittenham
Graphical abstract
