title: Microstructural brain abnormalities in Huntington's disease: A two-year follow-up.
abstract: OBJECTIVE
  To investigate both cross-sectional and time-related changes of striatal and whole-brain microstructural properties in different stages of Huntington's disease (HD) using diffusion tensor imaging.
  
  
  METHODS
  From the TRACK-HD study, premanifest gene carriers (preHD), early manifest HD and controls were scanned at baseline and 2-year follow-up. Stratification of the preHD group into a far (preHD-A) and near (preHD-B) to predicted disease onset was performed. Age-corrected histograms of whole-brain white matter (WM), gray matter (GM) and striatal diffusion measures were computed and normalised by the number of voxels in each subject's data set.
  
  
  RESULTS
  Higher cross-sectional mean, axial and radial diffusivities were found in both WM (P ≤ 0.001) and GM (P ≤ 0.001) of the manifest HD compared to the preHD and control groups. In preHD, only WM axial diffusivity (AD) was higher than in controls (P ≤ 0.01). This finding remained valid only in preHD-B (P ≤ 0.001). AD was also higher in the striatum of preHD-B compared to controls and preHD-A (P ≤ 0.01). Fractional anisotropy (FA) lacked sensitivity in differentiating between the groups. Histogram peak heights were generally lower in manifest HD compared to the preHD and control groups. No longitudinal differences were found in the degree of diffusivity change between the groups in the two year follow-up. There was a significant relationship between diffusivity and neurocognitive measures.
  
  
  CONCLUSIONS
  Alterations in cross-sectional diffusion profiles between manifest HD subjects and controls were evident, both in whole-brain and striatum. In the preHD stage, only AD alterations were found, a finding suggesting that this metric is a sensitive marker for early change in HD prior to disease manifestation. The individual diffusivities were superior to FA in revealing pathologic microstructural brain alterations. Diffusion measures were well related to clinical functioning and disease stage.
authors: Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
authors: Omar F F
authors: OF
authors: Odish
authors: Alexander
authors: A
authors: Leemans
authors: Robert H A M
authors: RH
authors: Reijntjes
authors: Simon J A
authors: SJ
authors: van den Bogaard
authors: Eve M
authors: EM
authors: Dumas
authors: Ron
authors: R
authors: Wolterbeek
authors: Chantal M W
authors: CM
authors: Tax
authors: Hugo J
authors: HJ
authors: Kuijf
authors: Koen L
authors: KL
authors: Vincken
authors: Jeroen
authors: J
authors: van der Grond
authors: Raymund A C
authors: RA
authors: Roos
mesh_terms: D000328:Adult; D016880:Anisotropy; D001921:Brain / Q000473:pathology*; D056324:Diffusion Tensor Imaging; D005260:Female; D005500:Follow-Up Studies; D066128:Gray Matter / Q000473:pathology; D006801:Humans; D006816:Huntington Disease / Q000473:pathology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D066127:White Matter / Q000473:pathology
keywords: Huntington's disease; TRACK-HD; cognitive; diffusion tensor imaging; gray matter; histogram analysis; longitudinal biomarker; premanifest; striatum; white matter
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