title: Profiles of white matter tract pathology in frontotemporal dementia.
abstract: Despite considerable interest in improving clinical and neurobiological characterisation of frontotemporal dementia and in defining the role of brain network disintegration in its pathogenesis, information about white matter pathway alterations in frontotemporal dementia remains limited. Here we investigated white matter tract damage using an unbiased, template-based diffusion tensor imaging (DTI) protocol in a cohort of 27 patients with the behavioral variant of frontotemporal dementia (bvFTD) representing both major genetic and sporadic forms, in relation both to healthy individuals and to patients with Alzheimer's disease. Widespread white matter tract pathology was identified in the bvFTD group compared with both healthy controls and Alzheimer's disease group, with prominent involvement of uncinate fasciculus, cingulum bundle and corpus callosum. Relatively discrete and distinctive white matter profiles were associated with genetic subgroups of bvFTD associated with MAPT and C9ORF72 mutations. Comparing diffusivity metrics, optimal overall separation of the bvFTD group from the healthy control group was signalled using radial diffusivity, whereas optimal overall separation of the bvFTD group from the Alzheimer's disease group was signalled using fractional anisotropy. Comparing white matter changes with regional grey matter atrophy (delineated using voxel based morphometry) in the bvFTD cohort revealed co-localisation between modalities particularly in the anterior temporal lobe, however white matter changes extended widely beyond the zones of grey matter atrophy. Our findings demonstrate a distributed signature of white matter alterations that is likely to be core to the pathophysiology of bvFTD and further suggest that this signature is modulated by underlying molecular pathologies.
authors: Dementia Research Centre, UCL Institute of Neurology, University College London, London, United Kingdom.
authors: Colin J
authors: CJ
authors: Mahoney
authors: Gerard R
authors: GR
authors: Ridgway
authors: Ian B
authors: IB
authors: Malone
authors: Laura E
authors: LE
authors: Downey
authors: Jonathan
authors: J
authors: Beck
authors: Kirsi M
authors: KM
authors: Kinnunen
authors: Nicole
authors: N
authors: Schmitz
authors: Hannah L
authors: HL
authors: Golden
authors: Jonathan D
authors: JD
authors: Rohrer
authors: Jonathan M
authors: JM
authors: Schott
authors: Martin N
authors: MN
authors: Rossor
authors: Sebastien
authors: S
authors: Ourselin
authors: Simon
authors: S
authors: Mead
authors: Nick C
authors: NC
authors: Fox
authors: Jason D
authors: JD
authors: Warren
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis / Q000473:pathology*; D016880:Anisotropy; D001284:Atrophy; D001921:Brain / Q000473:pathology*; D000073885:C9orf72 Protein; D015331:Cohort Studies; D056324:Diffusion Tensor Imaging; D005260:Female; D057180:Frontotemporal Dementia / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D060005:Genotyping Techniques; D066128:Gray Matter / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D011506:Proteins / Q000235:genetics; D012680:Sensitivity and Specificity; D066127:White Matter / Q000473:pathology*; D016875:tau Proteins / Q000235:genetics
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; C054369:MAPT protein, human; D011506:Proteins; D016875:tau Proteins
keywords: DTI; frontotemporal dementia; tract; tractography; white matter