E15 Structural Connectivity In Huntington’s Disease

Background Structural imaging in HD shows that widespread degeneration of white matter (WM) precedes that of grey matter and is associated with disease progression. Examining WM tracts that connect cortical and subcortical brain regions provides additional information regarding WM microstructure. Existing studies show disrupted connectivity in both premanifest and clinically diagnosed HD, but these have generally been small single-site studies and there is still uncertainty as to the precise nature of structural connectivity changes in HD. Aims To identify disease-related structural connectivity differences in HD gene carriers Methods Diffusion imaging data from the multi-site TrackHD study for 47 premanifest and 45 early-HD subjects were analysed using whole-brain Tract-Based Spatial Statistics. Four measures of diffusivity were analysed: fractional anisotropy (FA) - a surrogate marker for tract integrity; mean diffusivity (MD), plus axial (AD) and radial (RD) diffusivity–indicators of axonal degeneration and myelination respectively. Simple regression analyses were performed on all gene carriers to investigate the relationships between disease progression and WM diffusivity using two measures of disease load: clinical – cumulative probability to onset and structural – caudate volume. Results Reduced FA and increased levels of MD, AD and RD in WM tracts throughout the brain were positively correlated with disease progression. This was the case for both measures of disease load. Conclusions Abnormal WM microstructure is associated with HD disease progression. Reduced FA and increased MD commonly suggest a reduction in fibre organisation, while increased levels of axial and radial diffusivity suggest both axonal degeneration and reduced myelination in HD.