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Clinical, cognitive, and behavioural correlates of white matter damage in progressive supranuclear palsy

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Abstract

White matter (WM) tract alterations were assessed in patients with progressive supranuclear palsy (PSP) relative to healthy controls and patients with idiopathic Parkinson’s disease (PD) to explore the relationship of WM tract damage with clinical disease severity, performance on cognitive tests, and apathy. 37 PSP patients, 41 PD patients, and 34 healthy controls underwent an MRI scan and clinical testing to evaluate physical disability, cognitive impairment, and apathy. In PSP, the contribution of WM tract damage to global disease severity and cognitive and behavioural disturbances was assessed using Random Forest analysis. Relative to controls, PSP patients showed diffusion tensor (DT) MRI abnormalities of the corpus callosum, superior cerebellar peduncle (SCP), cingulum and uncinate fasciculus bilaterally, and right inferior longitudinal fasciculus. Corpus callosum and SCP DT MRI measures distinguished PSP from PD patients with high accuracy (area under the curve ranging from 0.89 to 0.72). In PSP, DT MRI metrics of the corpus callosum and superior cerebellar peduncles were the best predictors of global disease severity scale scores. DT MRI metrics of the corpus callosum, right superior longitudinal and inferior longitudinal fasciculus, and left uncinate were the best predictors of executive dysfunction. In PSP, apathy severity was related to the damage to the corpus callosum, right superior longitudinal, and uncinate fasciculi. In conclusion, WM tract damage contributes to the motor, cognitive, and behavioural deficits in PSP. DT MRI offers markers for PSP diagnosis, assessment, and monitoring.

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Acknowledgments

This project was partly supported by a grant from the Ministry of Science and Technology of the Republic of Serbia (Grant #175090) and a grant from the Italian Ministry of Health (Grant #GR-2009-1577482).

Conflicts of interest

Federica Agosta serves on the editorial board of the Journal of Neurology and has received research supports from the Italian Ministry of Health and AriSLA (Fondazione Italiana di ricerca per la Sclerosi Laterale Amiotrofica), funding for travel from Teva Pharmaceutical Industries Ltd., and speaker honoraria from Bayer Schering Pharma, Biogen Idec, Sanofi Aventis, and Serono Symposia International Foundation. Sebastiano Galantucci, Milica Ječmenica Lukić, Massimiliano Copetti, Kristina Davidovic, Aleksandra Tomić, and Edoardo G. Spinelli report no disclosures. Marina Svetel has received speaker honoraria from Glaxo-Smith-Kleine, Novartis, Boeringer-Ingelheim; and has received funding for travel from Boeringer-Ingelheim and Glaxo-Smith-Klein. Vladimir S. Kostic has received speaker honoraria from Novartis, Boehringer Ingelheim, Pfizer, Hemofarm-Stada, and GlaxoSmithKline and receives research support from the Ministry of Science and Technology of the Republic of Serbia, Pharmaswiss, and Boehringer Ingelheim. Massimo Filippi is Editor-in-Chief of the Journal of Neurology; serves on scientific advisory boards for Teva Pharmaceutical Industries and Genmab A/S; has received compensation for consulting services and/or speaking activities from Bayer Schering Pharma, Biogen Idec, Genmab A/S, Merck Serono, and Teva Pharmaceutical Industries; and receives research support from Bayer Schering Pharma, Biogen Idec, Genmab A/S, Merck Serono, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, Cure PSP, and the Jacques and Gloria Gossweiler Foundation (Switzerland).

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Authors and Affiliations

  1. Neuroimaging Research Unit, Division of Neuroscience, Institute of Experimental Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina, 60, 20132, Milan, Italy

    Federica Agosta, Sebastiano Galantucci, Edoardo G. Spinelli & Massimo Filippi

  2. Department of Neurology, Division of Neuroscience, Institute of Experimental Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy

    Edoardo G. Spinelli & Massimo Filippi

  3. Clinic of Neurology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia

    Marina Svetel, Milica Ječmenica Lukić, Kristina Davidovic, Aleksandra Tomić & Vladimir S. Kostić

  4. Biostatistics Unit, IRCCS-Ospedale Casa Sollievo della Sofferenza, Foggia, Italy

    Massimiliano Copetti

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  1. Federica Agosta
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  2. Sebastiano Galantucci
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  3. Marina Svetel
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  4. Milica Ječmenica Lukić
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Correspondence to Massimo Filippi.

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Agosta, F., Galantucci, S., Svetel, M. et al. Clinical, cognitive, and behavioural correlates of white matter damage in progressive supranuclear palsy. J Neurol 261, 913–924 (2014). https://doi.org/10.1007/s00415-014-7301-3

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  • DOI: https://doi.org/10.1007/s00415-014-7301-3

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