title: An advanced white matter tract analysis in frontotemporal dementia and early-onset Alzheimer's disease.
abstract: Cortical and subcortical nuclei degenerate in the dementias, but less is known about changes in the white matter tracts that connect them. To better understand white matter changes in behavioral variant frontotemporal dementia (bvFTD) and early-onset Alzheimer's disease (EOAD), we used a novel approach to extract full 3D profiles of fiber bundles from diffusion-weighted MRI (DWI) and map white matter abnormalities onto detailed models of each pathway. The result is a spatially complex picture of tract-by-tract microstructural changes. Our atlas of tracts for each disease consists of 21 anatomically clustered and recognizable white matter tracts generated from whole-brain tractography in 20 patients with bvFTD, 23 with age-matched EOAD, and 33 healthy elderly controls. To analyze the landscape of white matter abnormalities, we used a point-wise tract correspondence method along the 3D profiles of the tracts and quantified the pathway disruptions using common diffusion metrics - fractional anisotropy, mean, radial, and axial diffusivity. We tested the hypothesis that bvFTD and EOAD are associated with preferential degeneration in specific neural networks. We mapped axonal tract damage that was best detected with mean and radial diffusivity metrics, supporting our network hypothesis, highly statistically significant and more sensitive than widely studied fractional anisotropy reductions. From white matter diffusivity, we identified abnormalities in bvFTD in all 21 tracts of interest but especially in the bilateral uncinate fasciculus, frontal callosum, anterior thalamic radiations, cingulum bundles and left superior longitudinal fasciculus. This network of white matter alterations extends beyond the most commonly studied tracts, showing greater white matter abnormalities in bvFTD versus controls and EOAD patients. In EOAD, network alterations involved more posterior white matter - the parietal sector of the corpus callosum and parahipoccampal cingulum bilaterally. Widespread but distinctive white matter alterations are a key feature of the pathophysiology of these two forms of dementia.
authors.affiliation: Imaging Genetics Center, Mark & Mary Stevens Institute for Neuroimaging & Informatics, University of Southern California, Marina del Rey, CA, USA.|Department of Neurology, UCLA School of Medicine, Los Angeles, CA, USA.
authors.forename: Madelaine
authors.initials: M
authors.lastname: Daianu
authors.affiliation: Behavioral Neurology Program, Department of Neurology, UCLA, Los Angeles, CA, USA.
authors.forename: Mario F
authors.initials: MF
authors.lastname: Mendez
authors.affiliation: Imaging Genetics Center, Mark & Mary Stevens Institute for Neuroimaging & Informatics, University of Southern California, Marina del Rey, CA, USA.
authors.forename: Vatche G
authors.initials: VG
authors.lastname: Baboyan
authors.affiliation: Imaging Genetics Center, Mark & Mary Stevens Institute for Neuroimaging & Informatics, University of Southern California, Marina del Rey, CA, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Brain, Behavior, and Aging Research Center, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA.|Departments of Psychiatry and Biobehavioral Sciences, UCLA School of Medicine, Los Angeles, CA, USA.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Melrose
authors.affiliation: Behavioral Neurology Program, Department of Neurology, UCLA, Los Angeles, CA, USA.
authors.forename: Elvira E
authors.initials: EE
authors.lastname: Jimenez
authors.affiliation: Imaging Genetics Center, Mark & Mary Stevens Institute for Neuroimaging & Informatics, University of Southern California, Marina del Rey, CA, USA. pthomp@usc.edu.|Department of Neurology, UCLA School of Medicine, Los Angeles, CA, USA. pthomp@usc.edu.|Departments of Neurology, Psychiatry, Radiology, Engineering, Pediatrics, and Ophthalmology, University of Southern California, Los Angeles, CA, USA. pthomp@usc.edu.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Thompson
mesh_terms: D017668:Age of Onset; D000544:Alzheimer Disease / Q000000981:diagnostic imaging*; D001921:Brain / Q000000981:diagnostic imaging*; D015331:Cohort Studies; D038524:Diffusion Magnetic Resonance Imaging; D056324:Diffusion Tensor Imaging; D005260:Female; D057180:Frontotemporal Dementia / Q000000981:diagnostic imaging*; D006801:Humans; D021621:Imaging, Three-Dimensional; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D066127:White Matter / Q000000981:diagnostic imaging*
keywords: Behavioral variant frontotemporal dementia; Diffusion tensor imaging (DTI); Early-onset Alzheimer’s disease; Tract analysis; White matter