Corpus callosal atrophy in premanifest and early Huntington's disease.

BACKGROUND: Volumetric MRI studies have highlighted the pronounced loss of white matter in premanifest and early Huntington's Disease (HD). The current study focussed on the corpus callosum (CC) since it provides interhemispheric connections to vulnerable cortical areas. OBJECTIVES: To investigate cross-sectional and longitudinal group differences in CC volume and hypothesis-driven associations with three cognitive tasks. METHODS: Baseline and 24-month 3T MRI were analysed from 106 premanifest (PreHD), (59 preHD-A ≥10.8 and 47 preHD-B <10.8 years from predicted onset), 84 early HD (53 Stage 1 (HD1) and 31 Stage 2 (HD2)) and 101 control subjects from the TRACK-HD study, using a semi-automated technique for CC delineation. Between-group differences in volume and 24-month atrophy rates, and correlations with cognitive performance were investigated using regression models, adjusting for potential confounders. RESULTS: PreHD-B, HD1 and HD2 had statistically significantly smaller baseline CC volumes (p < 0.001) and all groups had elevated 24-month atrophy rates compared with controls (p < 0.001). Smaller baseline CC volume was associated with impaired performance in the Circle Tracing Indirect task in early HD (p < 0.05). Positive, non-statistically significant relationships with Stroop Word Reading were shown in both gene-positive groups. There was no evidence of an association with the Trail Making B task. CONCLUSIONS: We found reduced CC volume and elevated 24-month atrophy rates, even in individuals far from disease onset. Structural degeneration of interhemispheric connections may contribute to cognitive deficits, such as performance in the Circle Tracing Indirect task in HD. Examination of different image acquisitions may provide more specific information about underlying CC degeneration.

Evaluation of multi-modal, multi-site neuroimaging measures in Huntington's disease: Baseline results from the PADDINGTON study.

BACKGROUND: Macro- and micro-structural neuroimaging measures provide valuable information on the pathophysiology of Huntington's disease (HD) and are proposed as biomarkers. Despite theoretical advantages of microstructural measures in terms of sensitivity to pathology, there is little evidence directly comparing the two. METHODS: 40 controls and 61 early HD subjects underwent 3 T MRI (T1- and diffusion-weighted), as part of the PADDINGTON study. Macrostructural volumetrics were obtained for the whole brain, caudate, putamen, corpus callosum (CC) and ventricles. Microstructural diffusion metrics of fractional anisotropy (FA), mean-, radial- and axial-diffusivity (MD, RD, AD) were computed for white matter (WM), CC, caudate and putamen. Group differences were examined adjusting for age, gender and site. A formal comparison of effect sizes determined which modality and metrics provided a statistically significant advantage over others. RESULTS: Macrostructural measures showed decreased regional and global volume in HD (p < 0.001); except the ventricles which were enlarged (p < 0.01). In HD, FA was increased in the deep grey-matter structures (p < 0.001), and decreased in the WM (CC, p = 0.035; WM, p = 0.053); diffusivity metrics (MD, RD, AD) were increased for all brain regions (p < 0.001). The largest effect sizes were for putamen volume, caudate volume and putamen diffusivity (AD, RD and MD); each was significantly larger than those for all other metrics (p < 0.05). CONCLUSION: The highest performing macro- and micro-structural metrics had similar sensitivity to HD pathology quantified via effect sizes. Region-of-interest may be more important than imaging modality, with deep grey-matter regions outperforming the CC and global measures, for both volume and diffusivity. FA appears to be relatively insensitive to disease effects.