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BACKGROUND: Unbiased longitudinal studies are needed to understand the distributed neurodegenerative changes of Huntington's disease (HD). They may also provide tools for assessing disease-modifying interventions. The authors investigated the progression of regional atrophy in premanifest and early HD compared with controls. METHODS: Nine controls, 17 premanifest and 21 early HD subjects underwent volumetric MRI at baseline and 2 years. Premanifest subjects were on average 18.1 years before predicted motor onset. Non-linear registration was used to model within-subject change over the scanning interval, and statistical parametric mapping was used to examine group differences and associations with clinical variables. RESULTS: In early HD, increased grey-matter (GM) atrophy rates were evident throughout the subcortical GM and over selective cortical regions compared with controls. This group also demonstrated strikingly widespread increases in white-matter (WM) atrophy rates. The authors observed no significant differences between premanifest HD and controls. Longer CAG was associated with higher atrophy rates over large WM areas including brainstem and internal capsule and over small GM regions including thalamus and occipital cortex. Worse baseline motor score was associated with regionally increased rates in the thalamus, internal capsule and occipital lobe. Sample-size calculations indicate that 19 and 24 early HD subjects per treatment arm would need to complete a 2-year trial in order to detect a 50% reduction in WM and GM atrophy rates respectively. CONCLUSIONS: Degeneration of structural connectivity may play an important role in early HD symptoms. Assessment of WM and GM changes will be important in understanding the complexity of HD and its treatment.

Original publication




Journal article


J Neurol Neurosurg Psychiatry

Publication Date





756 - 763


Adult, Atrophy, Brain, Cohort Studies, Disease Progression, Female, Humans, Huntington Disease, Image Processing, Computer-Assisted, Longitudinal Studies, Magnetic Resonance Imaging, Male, Middle Aged, Models, Statistical, Movement, Regression Analysis, Repetitive Sequences, Nucleic Acid, Sample Size