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  Longitudinal diffusion tensor imaging resembles patterns of pathology progression in behavioral variant frontotemporal dementia (bvFTD)

Kassubek, J., Müller, H.-P., Del Tredici, K., Hornberger, M., Schroeter, M. L., Mueller, K., et al. (2018). Longitudinal diffusion tensor imaging resembles patterns of pathology progression in behavioral variant frontotemporal dementia (bvFTD). Frontiers in Aging Neuroscience, 10: 47. doi:10.3389/fnagi.2018.00047.

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Kassubek, Jan1, Author
Müller, Hans-Peter1, Author
Del Tredici, Kelly2, Author
Hornberger, Michael3, Author
Schroeter, Matthias L.4, Author           
Mueller, Karsten5, Author           
Anderl-Straub, Sarah1, Author
Uttner, Ingo1, Author
Grossman, Murray6, Author
Braak, Heiko2, Author
Hodges, John R.7, Author
Piguet, Olivier8, Author
Otto, Markus1, Author
Ludolph, Albert C.1, Author
1Department of Neurology, Ulm University, Germany, ou_persistent22              
2Clinical Neuroanatomy, Department of Neurology, Ulm University, Germany, ou_persistent22              
3Department of Clinical Neuroscience, University of Cambridge, United Kingdom, ou_persistent22              
4Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_634549              
5Methods and Development Unit Nuclear Magnetic Resonance, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_634558              
6Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA, ou_persistent22              
7School of Medical Sciences, University of New South Wales, Sydney, Australia, ou_persistent22              
8ARC Centre of Excellence in Cognition and its Disorders, Macquarie University, Sydney, Australia, ou_persistent22              


Free keywords: Frontotemporal lobar degeneration; Diffusion tensor imaging; Fractional anisotropy; Neuropathology; Staging
 Abstract: Objective: Recently, the characteristic longitudinal distribution pattern of the underlying phosphorylated TDP-43 (pTDP-43) pathology in the behavioral variant of frontotemporal dementia (bvFTD) excluding Pick's disease (PiD) across specific brain regions was described. The aim of the present study was to investigate whether in vivo investigations of bvFTD patients by use of diffusion tensor imaging (DTI) were consistent with these proposed patterns of progression. Methods: Sixty-two bvFTD patients and 47 controls underwent DTI in a multicenter study design. Of these, 49 bvFTD patients and 34 controls had a follow-up scan after ~12 months. Cross-sectional and longitudinal alterations were assessed by a two-fold analysis, i.e., voxelwise comparison of fractional anisotropy (FA) maps and a tract of interest-based (TOI) approach, which identifies tract structures that could be assigned to brain regions associated with disease progression. Results: Whole brain-based spatial statistics showed white matter alterations predominantly in the frontal lobes cross-sectionally and longitudinally. The TOIs of bvFTD neuroimaging stages 1 and 2 (uncinate fascicle—bvFTD pattern I; corticostriatal pathway—bvFTD pattern II) showed highly significant differences between bvFTD patients and controls. The corticospinal tract-associated TOI (bvFTD pattern III) did not differ between groups, whereas the differences in the optic radiation (bvFTD pattern IV) reached significance. The findings in the corticospinal tract were due to a “dichotomous” behavior of FA changes there. Conclusion: Longitudinal TOI analysis demonstrated a pattern of white matter pathways alterations consistent with patterns of pTDP-43 pathology.


Language(s): eng - English
 Dates: 2017-08-122018-02-122018-03-06
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.3389/fnagi.2018.00047
PMID: 29559904
PMC: PMC5845670
Other: eCollection 2018
 Degree: -



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Project name : German Consortium for Frontotemporal Lobar Degeneration
Grant ID : O1GI1007A
Funding program : -
Funding organization : German Federal Ministry of Education and Research (BMBF)
Project name : -
Grant ID : LU 336/15-1
Funding program : -
Funding organization : Deutsche Forschungsgemeinschaft (DFG)
Project name : -
Grant ID : APP1037746
Funding program : -
Funding organization : National Health and Medical Research Council (NHMRC)
Project name : Centre of Excellence in Cognition and its Disorders Memory Node
Grant ID : CE11000102
Funding program : -
Funding organization : Australian Research Council (ARC)
Project name : -
Grant ID : PDF-IRG-1307
Funding program : -
Funding organization : Parkinson's Disease Foundation
Project name : -
Grant ID : MJFF-11362
Funding program : -
Funding organization : Michael Fox Foundation
Project name : -
Grant ID : APP1103258
Funding program : Senior Research Fellowship
Funding organization : National Health and Medical Research Council (NHMRC)

Source 1

Title: Frontiers in Aging Neuroscience
  Abbreviation : Front Aging Neurosci
Source Genre: Journal
Publ. Info: Lausanne : Frontiers Research Foundation
Pages: - Volume / Issue: 10 Sequence Number: 47 Start / End Page: - Identifier: ISSN: 1663-4365
CoNE: https://pure.mpg.de/cone/journals/resource/1663-4365