Brain structure in preclinical Huntington's disease: a multi-method approach.
BACKGROUND
Structural magnetic resonance imaging (MRI) of the brain could be a powerful tool for discovering early biomarkers in clinically presymptomatic carriers of the Huntington's disease gene mutation (preHD). So far, structural changes have been found mainly in preHD approaching the estimated motor onset of the disease (i.e., less than 15 years from onset), whereas structural findings in preHD far from the estimated motor onset have been inconclusive.


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


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


RESULTS
VBM analyses did not reveal significant between-group differences, whereas cortical surface modeling and subcortical segmentation analyses showed significant regional cortical thinning and striatal changes in preHD compared to controls. Significant correlations were found between striatal structure, estimated time to motor onset and executive performance, whereas cortical changes were not significantly correlated with these parameters.


CONCLUSIONS
These data suggest that a combined methodological approach to structural MRI data could increase the sensitivity for detecting subtle neurobiological changes in early preHD. As consistently shown across different methods, the association between striatal structure and clinical measures supports the notion that changes in striatal volume could represent a more robust marker of disease progression than cortical changes.
Center of Psychosocial Medicine, Department of General Psychiatry, University of Heidelberg, Heidelberg, Germany. christian.wolf@med.uni-heidelberg.de
Robert Christian
RC
Wolf
Philipp Arthur
PA
Thomann
Anne Kerstin
AK
Thomann
Nenad
N
Vasic
Nadine Donata
ND
Wolf
G Bernhard
GB
Landwehrmeyer
Michael
M
Orth
D000328:Adult; D058070:Asymptomatic Diseases; D001921:Brain / Q000473:pathology*; D003071:Cognition; D003342:Corpus Striatum / Q000473:pathology*; D003627:Data Interpretation, Statistical; D018450:Disease Progression; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000175:diagnosis / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D013788:Thalamus / Q000473:pathology