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The relationship between clinical and pathological variables in Richardson’s syndrome

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Abstract

In order to determine the relationship between regional neuropathology and severity of clinical features in Richardson’s syndrome (PSP-RS), the following hypotheses were tested: (1) executive dysfunction relates to prefrontal pathology; (2) language difficulties to pathology in Broca’s area and/or the perirhinal cortex; and (3) visuospatial impairment to pathology in the supramarginal region. A prospectively studied case series of brain donors at a specialist clinic in Addenbrooke’s Hospital Cambridge, UK, were examined. All those fulfilling postmortem criteria for PSP-RS and their last cognitive assessment within 24 months of death (N = 11/25) were included. The degree of regional neuronal loss and neuronal tau deposition across a number of cortical brain regions was performed and compared to 10 age- and sex-matched controls from the Sydney Brain Bank. Stepwise multiple linear regressions were used to determine the neuropathological correlates to cognitive scores and revealed the following. Executive dysfunction, as indexed by letter fluency, related to the degree of tau deposition in the superior frontal gyrus and supramarginal cortices (p < 0.020), language deficits related to neuron loss in the perirhinal gyrus (p < 0.001) and tau deposition in Broca’s area (p = 0.020), while visuospatial dysfunction and global cognitive impairment related to tau deposition in the supramarginal gyrus (p < 0.007). The severity of cognitive deficits relate to regional cortical tau deposition in PSP-RS, although language impairment related to neuronal loss in the perirhinal region. Global cognitive dysfunction related most to the severity of tau deposition in the supramarginal gyrus warranting further research on the role of this brain region in PSP-RS.

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Acknowledgments

Tissues were received from the Cambridge Brain Bank, which is supported by the Medical Research Council, UK and the Sydney Brain Bank, which is supported by the National Health and Medical Research Council (NHMRC) of Australia (Enabling Grant 282933 & 052009), Neuroscience Research Australia and the University of New South Wales. The study was supported through research grants from the PSP Association. ES was supported by a NHMRC biomedical postgraduate research scholarship 300672. JH was supported by an ARC Federation Fellowship. GH was supported by a NHMRC Senior Principal Research Fellowships 350827 & 630434.

Conflict of interest

The authors declare that they have no conflict of interest and have no further financial disclosures to make.

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Authors and Affiliations

  1. Neuroscience Research Australia and the University of New South Wales, Barker Street, Randwick, Sydney, NSW 2031, Australia

    Emma C. Schofield, John R. Hodges & Glenda M. Halliday

  2. Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK

    John R. Hodges

  3. MRC Cognition and Brain Sciences Unit, Cambridge, UK

    John R. Hodges

  4. Department of Pathology, University of Cambridge, Cambridge, UK

    John H. Xuereb

  5. Human Cognitive Neuroscience, University of Edinburgh, Edinburgh, UK

    Thomas H. Bak

  6. Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK

    Thomas H. Bak

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  1. Emma C. Schofield
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  2. John R. Hodges
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  5. Glenda M. Halliday
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Correspondence to John R. Hodges.

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Schofield, E.C., Hodges, J.R., Bak, T.H. et al. The relationship between clinical and pathological variables in Richardson’s syndrome. J Neurol 259, 482–490 (2012). https://doi.org/10.1007/s00415-011-6205-8

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  • DOI: https://doi.org/10.1007/s00415-011-6205-8

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