Longitudinal white matter changes in frontotemporal dementia subtypes

Abstract

Frontotemporal lobe dementia is a degenerative brain condition characterised by focal atrophy affecting the frontal and temporal lobes predominantly. Changes in white matter with disease progression and their relationship to grey matter atrophy remain unknown in FTD. This study aimed to establish longitudinal white matter changes and compare these changes to regional grey matter atrophy in the main FTD subtypes Diffusion and T1-weighted images were collected from patients with behavioural-variant FTD (bvFTD: 12), progressive nonfluent aphasia (PNFA: 10), semantic dementia (SD: 11) , and 15 controls12 months apart. Changes in white matter integrity were established using fractional anisotropy, mean, axial and radial diffusivity measurements and patterns of cortical grey matter atrophy were measured using voxel-based morphometry. At baseline, bvFTD showed severe white matter changes in orbitofrontal and anterior temporal tracts, which progressed to involve posterior temporal and occipital white matter. In PNFA, initial degeneration occurred bilaterally in frontotemporal white matter (left > right), with subsequent changes more prominent on the right. Initial white matter changes in SD were circumscribed to the left temporal lobe, with subsequent changes extending to bilateral frontotemporal tracts. In contrast, progression of grey matter change over time was less pronounced in all FTD subtypes. Mean diffusivity was most sensitive in detecting baseline changes while fractional anisotropy and radial diffusivity revealed greatest changes over time, possibly reflecting different underlying pathological processes with disease progression. Our results indicate that investigations of white matter changes appear to be a sensitive approach to detect disease progression in FTD subtypes.