title: Elevated brain iron is independent from atrophy in Huntington's Disease.
abstract: Increased iron in subcortical structures in patients with Huntington's Disease (HD) has been suggested as a causal factor of neuronal degeneration. The present study examines iron accumulation, measured using magnetic resonance imaging (MRI), in premanifest gene carriers and in early HD patients as compared to healthy controls. In total 27 early HD patients, 22 premanifest gene carriers and 25 healthy controls, from the Leiden site of the TRACK-HD study, underwent 3T MRI including high resolution 3D T(1)- and T(2)-weighted and asymmetric spin echo (ASE) sequences. Magnetic Field Correlation (MFC) maps of iron levels were constructed to assess magnetic field inhomogeneities and compared between groups in the caudate nucleus, putamen, globus pallidus, hippocampus, amygdala, accumbens nucleus, and thalamus. Subsequently the relationship of MFC value to volumetric data and disease state was examined. Higher MFC values were found in the caudate nucleus (p<0.05) and putamen (p<0.005) of early HD compared to controls and premanifest gene carriers. No differences in MFC were found between premanifest gene carriers and controls. MFC in the caudate nucleus and putamen is a predictor of disease state in HD. No correlation was found between the MFC value and volume of these subcortical structures. We conclude that Huntington's disease patients in the early stages of the disease, but not premanifest gene carriers, have higher iron concentrations in the caudate nucleus and putamen. We have demonstrated that the iron content of these structures relates to disease state in gene carriers, independently of the measured volume of these structures.
authors.affiliation: Department of Neurology, Leiden University Medical Center, The Netherlands. e.m.dumas@lumc.nl
authors.forename: Eve M
authors.initials: EM
authors.lastname: Dumas
authors.forename: Maarten J
authors.initials: MJ
authors.lastname: Versluis
authors.forename: Simon J A
authors.initials: SJ
authors.lastname: van den Bogaard
authors.forename: Matthias J P
authors.initials: MJ
authors.lastname: van Osch
authors.forename: Ellen P
authors.initials: EP
authors.lastname: Hart
authors.forename: Willeke M C
authors.initials: WM
authors.lastname: van Roon-Mom
authors.forename: Mark A
authors.initials: MA
authors.lastname: van Buchem
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Webb
authors.forename: Jeroen
authors.initials: J
authors.lastname: van der Grond
authors.forename: Raymund A C
authors.initials: RA
authors.lastname: Roos
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000375:Aging / Q000502:physiology; D001284:Atrophy; D001921:Brain / Q000473:pathology*; D001923:Brain Chemistry / Q000502:physiology*; D002421:Caudate Nucleus / Q000378:metabolism; D018450:Disease Progression; D004522:Educational Status; D004574:Electromagnetic Fields; D005260:Female; D006579:Heterozygote; D006801:Humans; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D007091:Image Processing, Computer-Assisted; D007501:Iron / Q000378:metabolism*; D016015:Logistic Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011699:Putamen / Q000378:metabolism; D012727:Sex Characteristics
chemical_list: D007501:Iron