White matter abnormalities in Parkinson's disease patients with glucocerebrosidase gene mutations

Authors

  • Federica Agosta MD, PhD,

    1. Neuroimaging Research Unit, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
    Search for more papers by this author
  • Vladimir S. Kostic MD,

    1. Clinic of Neurology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
    Search for more papers by this author
  • Kristina Davidovic MD,

    1. Neuroimaging Research Unit, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
    2. Clinic of Neurology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
    Search for more papers by this author
  • Nikola Kresojević MD,

    1. Clinic of Neurology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
    Search for more papers by this author
  • Lidia Sarro MD,

    1. Neuroimaging Research Unit, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
    2. Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
    Search for more papers by this author
  • Marina Svetel MD,

    1. Clinic of Neurology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
    Search for more papers by this author
  • Iva Stanković MD,

    1. Clinic of Neurology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
    Search for more papers by this author
  • Giancarlo Comi MD,

    1. Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
    Search for more papers by this author
  • Christine Klein MD,

    1. Section of Clinical and Molecular Neurogenetics, Department of Neurology, University of Lubeck, Luebeck, Germany
    Search for more papers by this author
  • Massimo Filippi MD

    Corresponding author
    1. Neuroimaging Research Unit, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
    2. Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
    • Correspondence to: Prof. Massimo Filippi, Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina, 60, 20132 Milan, Italy; m.filippi@hsr.it.

    Search for more papers by this author

  • Funding agencies: This study was partially supported by a grant from the Italian Ministry of Health (grant GR-2009–1577482) and the Ministry of Science and Technology of the Republic of Serbia (grant 175095).

  • Relevant conflicts of interest/financial disclosures: Nothing to disclose.

  • Full financial disclosures may be found in the online version of the article.

ABSTRACT

Glucocerebrosidase gene mutations represent a genetic risk factor for the development of Parkinson's disease. This study investigated brain alterations in Parkinson's disease patients carrying heterozygous glucocerebrosidase gene mutations using structural and diffusion tensor magnetic resonance imaging. Among 360 Parkinson's disease patients screened for glucocerebrosidase gene mutations, 19 heterozygous mutation carriers (5.3%) were identified. Of these, 15 patients underwent a neuropsychological evaluation and a magnetic resonance imaging scan. Sixteen age- and sex-matched healthy controls and 14 idiopathic Parkinson's disease patients without glucocerebrosidase gene mutations were also studied. Tract-based spatial statistics was used to perform a white matter voxel-wise analysis of diffusion tensor magnetic resonance imaging metrics. Mean fractional anisotropy values were obtained from white matter tracts of interest. Voxel-based morphometry was used to assess gray-matter atrophy. Cognitive deficits were found in 9 mutation carrier patients (60%). Compared with controls, Parkinson's disease patients carrying glucocerebrosidase gene mutations showed decreased fractional anisotropy in the olfactory tracts, corpus callosum, and anterior limb of the internal capsule bilaterally, as well as in the right anterior external capsule, and left cingulum, parahippocampal tract, parietal portion of the superior longitudinal fasciculus, and occipital white matter. Mutation carrier patients also had decreased fractional anisotropy of the majority of white matter tracts compared with Parkinson's disease patients with no mutations. No white matter abnormalities were found in Parkinson's disease patients without glucocerebrosidase gene mutations. No gray matter difference was found between patients and controls. In Parkinson's disease patients, verbal fluency scores correlated with white matter abnormalities. Parkinson's disease patients carrying glucocerebrosidase gene mutations experience a distributed pattern of white matter abnormalities involving the interhemispheric, frontal corticocortical, and parahippocampal tracts. White matter pathology in these patients may have an impact on the clinical manifestations of the disease, including cognitive impairment. © 2013 Movement Disorder Society

Ancillary