title: Clinical impairment in premanifest and early Huntington's disease is associated with regionally specific atrophy.
abstract: TRACK-HD is a multicentre longitudinal observational study investigating the use of clinical assessments and 3-Tesla magnetic resonance imaging as potential biomarkers for future therapeutic trials in Huntington's disease (HD). The cross-sectional data from this large well-characterized dataset provide the opportunity to improve our knowledge of how the underlying neuropathology of HD may contribute to the clinical manifestations of the disease across the spectrum of premanifest (PreHD) and early HD. Two hundred and thirty nine gene-positive subjects (120 PreHD and 119 early HD) from the TRACK-HD study were included. Using voxel-based morphometry (VBM), grey and white matter volumes were correlated with performance in four domains: quantitative motor (tongue force, metronome tapping, and gait); oculomotor [anti-saccade error rate (ASE)]; cognition (negative emotion recognition, spot the change and the University of Pennsylvania smell identification test) and neuropsychiatric measures (apathy, affect and irritability). After adjusting for estimated disease severity, regionally specific associations between structural loss and task performance were found (familywise error corrected, P < 0.05); impairment in tongue force, metronome tapping and ASE were all associated with striatal loss. Additionally, tongue force deficits and ASE were associated with volume reduction in the occipital lobe. Impaired recognition of negative emotions was associated with volumetric reductions in the precuneus and cuneus. Our study reveals specific associations between atrophy and decline in a range of clinical modalities, demonstrating the utility of VBM correlation analysis for investigating these relationships in HD.
authors.affiliation: Department of Neurodegenerative Disease, UCL Institute of Neurology, London, United Kingdom. r.scahill@ion.ucl.ac.uk
authors.forename: Rachael I
authors.initials: RI
authors.lastname: Scahill
authors.forename: Nicola Z
authors.initials: NZ
authors.lastname: Hobbs
authors.forename: Miranda J
authors.initials: MJ
authors.lastname: Say
authors.forename: Natalie
authors.initials: N
authors.lastname: Bechtel
authors.forename: Susie M D
authors.initials: SM
authors.lastname: Henley
authors.forename: Harpreet
authors.initials: H
authors.lastname: Hyare
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Langbehn
authors.forename: Rebecca
authors.initials: R
authors.lastname: Jones
authors.forename: Blair R
authors.initials: BR
authors.lastname: Leavitt
authors.forename: Raymund A C
authors.initials: RA
authors.lastname: Roos
authors.forename: Alexandra
authors.initials: A
authors.lastname: Durr
authors.forename: Hans
authors.initials: H
authors.lastname: Johnson
authors.forename: Stéphane
authors.initials: S
authors.lastname: Lehéricy
authors.forename: David
authors.initials: D
authors.lastname: Craufurd
authors.forename: Christopher
authors.initials: C
authors.lastname: Kennard
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Hicks
authors.forename: Julie C
authors.initials: JC
authors.lastname: Stout
authors.forename: Ralf
authors.initials: R
authors.lastname: Reilmann
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Tabrizi
mesh_terms: D000328:Adult; D001284:Atrophy / Q000209:etiology; D001921:Brain / Q000473:pathology*; D001931:Brain Mapping; D003072:Cognition Disorders / Q000209:etiology / Q000473:pathology; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D020233:Gait Disorders, Neurologic / Q000209:etiology / Q000473:pathology; D006801:Humans; D006816:Huntington Disease / Q000150:complications* / Q000473:pathology*; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D015835:Ocular Motility Disorders / Q000209:etiology / Q000473:pathology; D011596:Psychomotor Disorders / Q000209:etiology / Q000473:pathology; D014059:Tongue / Q000503:physiopathology
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