Clinical impairment in premanifest and early Huntington's disease is associated with regionally specific atrophy

• Published in: Human brain mapping Vol. 34; no. 3; pp. 519 - 529
• Main Authors: Scahill, Rachael I., Hobbs, Nicola Z., Say, Miranda J., Bechtel, Natalie, Henley, Susie M.D., Hyare, Harpreet, Langbehn, Douglas R., Jones, Rebecca, Leavitt, Blair R., Roos, Raymund A.C., Durr, Alexandra, Johnson, Hans, Lehéricy, Stéphane, Craufurd, David, Kennard, Christopher, Hicks, Stephen L., Stout, Julie C., Reilmann, Ralf, Tabrizi, Sarah J.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.03.2013; Wiley-Liss; John Wiley & Sons, Inc
• Subjects: Adult; Atrophy - etiology; Biological and medical sciences; Brain - pathology; Brain Mapping; Cognition Disorders - etiology; Cognition Disorders - pathology; Cohort Studies; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease Progression; Female; Gait Disorders, Neurologic - etiology; Gait Disorders, Neurologic - pathology; Humans; Huntington Disease - complications; Huntington Disease - pathology; Image Processing, Computer-Assisted; Investigative techniques, diagnostic techniques (general aspects); Magnetic Resonance Imaging; Male; Medical sciences; Middle Aged; Nervous system; Neurology; Neuropsychological Tests; Ocular Motility Disorders - etiology; Ocular Motility Disorders - pathology; Psychomotor Disorders - etiology; Psychomotor Disorders - pathology; Radiodiagnosis. Nmr imagery. Nmr spectrometry; Tongue - physiopathology; TRACK-HD; voxel-based morphometry; TRACK-HD; Nervous system diseases; magnetic resonance imaging; Radiodiagnosis; Huntington disease; voxel-based morphometry; Nuclear magnetic resonance imaging; Genetic disease; Cerebral disorder; Atrophy; Voxel; Central nervous system disease; Degenerative disease; Morphometry; Extrapyramidal syndrome
• ISSN: 1065-9471; 1097-0193
• DOI: 10.1002/hbm.21449

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. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.