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Imaging
G02 Brain structure in preclinical Huntington's disease: a multi-method approach
  1. RC Wolf1,2,
  2. PA Thomann1,
  3. AK Thomann1,
  4. N Vasic2,
  5. ND Wolf3,
  6. GB Landwehrmeyer4,
  7. M Orth4
  1. 1Department of General Psychiatry, Center of Psychosocial Medicine, University of Heidelberg, Heidelberg, Germany
  2. 2Department of Psychiatry and Psychotherapy III, University of Ulm, Ulm, Germany
  3. 3Central Institute of Mental Health, Mannheim, Germany
  4. 4Department of Neurology, University of Ulm, Ulm, Germany

Abstract

Background Structural MRI of the brain could be a powerful tool for discovering early biomarkers in clinically pre-symptomatic carriers of the Huntington's disease gene mutation (preHD).

Aims The aim of this study was to investigate the sensitivity of different methodological approaches to structural data in far-from onset preHD (mean time to motor onset = 21.4 years) and to explore the relationship between the time to motor onset, cognition and brain structure.

Methods High-resolution MRI data at 3 Tesla were obtained from 20 preHD individuals and 20 healthy participants and subsequently analysed using voxel-based morphometry (VBM), cortical surface modelling and subcortical segmentation analysis techniques.

Results VBM analyses did not reveal significant between-group differences. In contrast, cortical surface modelling and subcortical segmentation analyses showed significant regional cortical thinning and striatal changes in preHD compared to controls (p<0.05, corrected for multiple comparisons). Significant correlations were found between striatal structure, time-to-motor-onset and behavioural performance during card sorting, whereas cortical changes were not significantly correlated with time-to-motor-onset or behavioural parameters.

Conclusions These data suggest that a combined methodological approach to structural MRI data could increase sensitivity to very early neurobiological changes in far-from-onset preHD. As demonstrated across different methodological modalities, the association between striatal structure and clinical measures supports the notion that striatal volume might represent a more robust marker of change than cortical alterations.

  • Voxel-based-morphometry
  • striatum
  • neuropsychology

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