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Reduced Cerebral White Matter Integrity Assessed by DTI in Cognitively Normal H63D‐HFE Polymorphism Carriers
Author(s) -
Meadowcroft Mark D.,
Wang Jianli,
Purnell Carson J.,
Eslinger Paul J.,
Neely Elizabeth B.,
Yang Qing X.,
Connor James R.
Publication year - 2017
Publication title -
journal of neuroimaging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.822
H-Index - 64
eISSN - 1552-6569
pISSN - 1051-2284
DOI - 10.1111/jon.12461
Subject(s) - white matter , fractional anisotropy , diffusion mri , medicine , magnetic resonance imaging , single nucleotide polymorphism , myelin , nuclear magnetic resonance , pathology , endocrinology , genetics , biology , genotype , central nervous system , physics , gene , radiology
ABSTRACT BACKGROUND AND PURPOSE The H63D‐HFE single nucleotide polymorphism (SNP) has been associated with brain iron dysregulation; however, the emergent role of this missense variant in brain structure and function has yet to be determined. Previous work has demonstrated that HFE SNP carriers have reduced white matter magnetic resonance imaging (MRI) proton relaxation rates. The mechanism by which white matter alterations perturb MRI relaxation is unknown as is how these metrics are related to myelin integrity. METHODS Fifteen subjects heterozygous for the HFE‐H63D SNP and 25 controls with wild‐type HFE had diffusion‐weighted, anatomical MRIs taken, and underwent cognitive assessment. Fractional anisotropy (FA), mean diffusion (MD), and mode of anisotropy (MO) were calculated from the diffusion dataset to investigate the relationship between the H63D‐HFE SNP and myelin integrity. RESULTS A decrease in FA, an increase in MD, and an increase in MO are demonstrated in multiple H63D‐HFE polymorphism carrier white matter tracts. Regions with altered diffusion metrics are notably located in heavily myelinated white matter association fibers, such as the anterior corona radiata and longitudinal fasciculi. CONCLUSIONS The MRI data presented here demonstrate that H63D‐HFE polymorphism carriers have diffusivity changes in white matter compared to wild‐type subjects. The reduced integrity white matter tracts in H63D‐HFE carriers are hypothesized to be related to increased susceptibility of these late‐myelinating regions to cellular stress induced by oligodendrocyte iron dyshomeostasis.