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Whole-brain white matter disruption in semantic and nonfluent variants of primary progressive aphasia

Authors

  • Graeme C. Schwindt,

    Corresponding author
    1. Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada
    2. L.C. Campbell Cognitive Neurology Research Unit, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
    3. Brain Sciences Research Program, Sunnybrook Research Institute, Toronto, Ontario, Canada
    • Sunnybrook Health Sciences Centre, Room A-421, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada
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  • Naida L. Graham,

    1. Department of Speech-Language Pathology, University of Toronto, Toronto, Ontario, Canada
    2. Toronto Rehabilitation Institute, Toronto, Ontario, Canada
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  • Elizabeth Rochon,

    1. Department of Speech-Language Pathology, University of Toronto, Toronto, Ontario, Canada
    2. Toronto Rehabilitation Institute, Toronto, Ontario, Canada
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  • David F. Tang-Wai,

    1. Department of Medicine (Neurology), University of Toronto, Toronto, Ontario, Canada
    2. Division of Neurology, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada
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  • Nancy J. Lobaugh,

    1. L.C. Campbell Cognitive Neurology Research Unit, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
    2. Brain Sciences Research Program, Sunnybrook Research Institute, Toronto, Ontario, Canada
    3. Department of Medicine (Neurology), University of Toronto, Toronto, Ontario, Canada
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  • Tiffany W. Chow,

    1. Department of Medicine (Neurology), University of Toronto, Toronto, Ontario, Canada
    2. Rotman Research Institute, Toronto, Ontario, Canada
    3. Department of Psychiatry (Geriatric Psychiatry), University of Toronto, Toronto, Ontario, Canada
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  • Sandra E. Black

    1. Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada
    2. L.C. Campbell Cognitive Neurology Research Unit, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
    3. Brain Sciences Research Program, Sunnybrook Research Institute, Toronto, Ontario, Canada
    4. Toronto Rehabilitation Institute, Toronto, Ontario, Canada
    5. Department of Medicine (Neurology), University of Toronto, Toronto, Ontario, Canada
    6. Rotman Research Institute, Toronto, Ontario, Canada
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Abstract

Semantic (svPPA) and nonfluent (nfPPA) variants of primary progressive aphasia are associated with distinct patterns of cortical atrophy and underlying pathology. Little is known, however, about their contrasting spread of white matter disruption and how this relates to grey matter (GM) loss. We undertook a structural MRI study to investigate this relationship. We used diffusion tensor imaging, tract-based spatial statistics, and voxel-based morphometry to examine fractional anisotropy (FA) and directional diffusivities in nine patients with svPPA and nine patients with nfPPA, and compared them to 16 matched controls after accounting for global GM atrophy. Significant differences in topography of white matter changes were found, with more ventral involvement in svPPA patients and more widespread frontal involvement in nfPPA individuals. However, each group had both ventral and dorsal tract changes, and both showed spread of diffusion abnormalities beyond sites of local atrophy. There was a clear dissociation in sensitivity of diffusion tensor imaging measures between groups. SvPPA patients showed widespread changes in FA and radial diffusivity, whereas changes in axial diffusivity were more restricted and proximal to sites of GM atrophy. NfPPA patients showed isolated changes in FA, but widespread axial and radial diffusivity changes. These findings reveal the extent of white matter disruption in these variants of PPA after accounting for GM loss. Further, they suggest that differences in the relative sensitivity of diffusion metrics may reflect differences in the nature of underlying white matter pathology in these two subtypes. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.

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