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Executive dysfunction in frontotemporal dementia is related to abnormalities in frontal white matter tracts

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Abstract

Cognitive deficits in behavioral-variant frontotemporal dementia (bvFTD) and AD are linked to frontal and temporal lobe gray matter (GM) pathology. The aim of this study was to assess the relative contribution of white (WM) and GM abnormalities to cognitive dysfunction in bvFTD and AD. Fractional anisotropy (FA) for the corpus callosum, cingulum (Cg), and uncinate fasciculus (Unc) was determined in 17 bvFTD and 10 AD patients who underwent neuropsychological testing. Regressions were performed to assess the relative contribution of WM and GM abnormalities to cognitive deficits. Multiple regression analysis revealed that in bvFTD, the left anterior Cg FA was related to executive function, the right anterior Cg FA to visual-spatial attention and working memory, the right posterior Cg to visual-constructional abilities and the left Unc FA to Modified Trails Errors. After adding corresponding GM volumes, the left anterior Cg FA, the right anterior cingulate FA, the right posterior cingulate FA and the left uncinate FA remained significant predictors of the cognitive tasks. In the AD group, the left posterior Cg FA and right descending Cg FA were related to visual recall performance but did not remain significant predictors when GM volumes were added to the regression. These results suggest that reduced integrity of specific WM tracts contribute to cognitive deficits observed in bvFTD after accounting for GM atrophy. In AD, memory impairment was related to WM tract injury but this relationship was no longer observed when GM volumes were included.

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Acknowledgments

We thank the participants and their families for their participation in this study. We thank Will Irwin for assistance with the figures. This publication was made possible by Grant numbers P01 AG019724 and P50 AG023501 from NIH National Institute on Aging. MCT is supported by Fonds de la recherche en santé du Québec.

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Authors and Affiliations

  1. Department of Neurology, Memory and Aging Center, University of California, San Francisco, CA, USA

    M. C. Tartaglia, V. Laluz, J. Neuhaus, J. Kramer, H. Rosen & B. Miller

  2. Neurology Clinic/Memory Clinic, Toronto Western Hospital, University of Toronto, West Wing 5-449, 399 Bathurst St., Toronto, ON, M5T 2S8, Canada

    M. C. Tartaglia

  3. Department of Radiology, Center for Imaging of Neurodegenerative Diseases, VA Medical Center, University of California San Francisco, San Francisco, CA, USA

    Y. Zhang, L. Chao & M. Weiner

  4. Departments of Neurological Surgery and Radiation Oncology, University of California, San Francisco, CA, USA

    C. Racine

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  1. M. C. Tartaglia
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  4. V. Laluz
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  5. J. Neuhaus
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Correspondence to M. C. Tartaglia.

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Tartaglia, M.C., Zhang, Y., Racine, C. et al. Executive dysfunction in frontotemporal dementia is related to abnormalities in frontal white matter tracts. J Neurol 259, 1071–1080 (2012). https://doi.org/10.1007/s00415-011-6300-x

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  • DOI: https://doi.org/10.1007/s00415-011-6300-x

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