Dataset Information

Reduced Cerebral White Matter Integrity Assessed by DTI in Cognitively Normal H63D-HFE Polymorphism Carriers.

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.

SUBMITTER: Meadowcroft MD

PROVIDER: S-EPMC5760459 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Reduced Cerebral White Matter Integrity Assessed by DTI in Cognitively Normal H63D-HFE Polymorphism Carriers.

Meadowcroft Mark D MD Wang Jianli J Purnell Carson J CJ Eslinger Paul J PJ Neely Elizabeth B EB Yang Qing X QX Connor James R JR

Journal of neuroimaging : official journal of the American Society of Neuroimaging 20170803 1

<h4>Background and purpose</h4>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 ...[more]

PMID: 28771940

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Project description:IntroductionAlzheimer's disease (AD) is a neurodegenerative disorder characterized by changes in beta amyloid (Aß) and tau as well as changes in cerebral glucose metabolism and gray matter volume. This has been categorized as three distinct stages of amyloid, tau, and neurodegeneration. Past studies have shown asymmetric Aβ accumulation and its association with asymmetric cerebral metabolism in preclinical AD. We analyzed data to replicate these findings and extend them to associations with gray matter volume and cognitive function.MethodsWe recruited 93 (mean age = 76.4±6.1 years) cognitively normal adults who underwent magnetic resonance imaging (MRI) and positron emission tomography (PET) with Pittsburgh compound B (PiB) and Fluorodeoxyglucose (FDG) tracers (to estimate Aβ and glucose metabolism, respectively). We conducted voxel-wise paired t-test on PiB (left vs. right hemispheres) to identify regions that differ in Aβ between the left and right cortex. We identified whether these regions showed asymmetry in FDG and gray matter volume using paired t-tests on each region. We then conducted correlations between asymmetry indices for each region that had significant asymmetry in PiB, FDG, and gray matter volume. We ran a group regression analysis on cognitive functions.ResultsWe found 26 regions that had significant rightward asymmetry in PiB including prefrontal cortex, temporal cortex, insula, parahippocampus, caudate, and putamen. All these regions showed significant gray matter rightward asymmetry, and most of these regions showed significant FDG asymmetry except the caudate, orbital cortex, medial frontal gyrus, and superior temporal gyrus. Only in the superior frontal gyrus, we found that greater rightward asymmetry in PiB was associated with greater rightward asymmetry in FDG, r(82) =0.38, p<0.005 (FDR corrected) - no other regions showed significant Aß asymmetry correlation with either FDG or gray matter volume asymmetry. We found that greater rightward FDG asymmetry in the superior frontal gyrus was associated with greater visuospatial processing scores in our cognitive domain group regression analysis.DiscussionAD has previously been modeled in three-stages: however, our results indicate that cerebral glucose metabolism may be dynamic throughout the disease progression and may serve as a compensatory pathway for maintaining cognitive functioning.

Dataset Information

Reduced Cerebral White Matter Integrity Assessed by DTI in Cognitively Normal H63D-HFE Polymorphism Carriers.

Publications

Reduced Cerebral White Matter Integrity Assessed by DTI in Cognitively Normal H63D-HFE Polymorphism Carriers.

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