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β-amyloid and postural instability and gait difficulty in Parkinson's disease at risk for dementia

Authors

  • Martijn L.T.M. Müller PhD,

    Corresponding author
    • Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA
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  • Kirk A. Frey MD, PhD,

    1. Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA
    2. Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA
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  • Myria Petrou MA, MBChB, MS,

    1. Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA
    2. Russell H. Morgan Department of Radiology, Johns Hopkins University, Baltimore, Maryland, USA
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  • Vikas Kotagal MD,

    1. Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA
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  • Robert A. Koeppe PhD,

    1. Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA
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  • Roger L. Albin MD,

    1. Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA
    2. Neurology Service and GRECC, VAAAHS, Ann Arbor, Michigan, USA
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  • Nicolaas I. Bohnen MD, PhD

    1. Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA
    2. Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA
    3. Neurology Service and GRECC, VAAAHS, Ann Arbor, Michigan, USA
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  • Funding agencies: This work was supported by National Institutes of Health (grant nos.: P01 NS015655 and R01 NS070856), the Michael J. Fox Foundation, and the Department of Veterans Affairs.

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

  • Full financial disclosures and author roles may be found in the online version of this article.

Correspondence to: Dr. Martijn L.T.M. Müller, Department of Radiology, Division of Nuclear Medicine, Functional Neuroimaging, Cognitive, and Mobility Laboratory, University of Michigan, 24 Frank LLoyd Wright Dr, Box #362, Ann Arbor MI 48105, USA; mtmuller@med.umich.edu

Abstract

Although motor impairments in Parkinson's disease (PD) are attributed to nigrostriatal dopaminergic denervation, postural instability and gait difficulty (PIGD) features are less responsive to dopaminergic medications. PIGD features are a risk factor also for the development of dementia in PD (PDD). These observations suggest that nondopaminergic mechanisms may contribute to axial motor impairments. The aim was to perform a correlative PET study to examine the relationship between neocortical β-amyloid deposition ([11C]-Pittsburgh Compound B), nigrostriatal dopaminergic denervation ([11C]-dihydrotetrabenazine), and PIGD feature severity in PD patients at risk for dementia. This was a cross-sectional study of 44 PD patients (11 female and 33 male; 69.5 ± 6.6 years of age; 7.0 ± 4.8 years motor disease duration; mean H & Y stage: 2.7 ± 0.5) who underwent PET, motor feature severity assessment using the Movement Disorder Society revised UPDRS, and the Dementia Rating Scale (DRS). Linear regression (R2adj = 0.147; F4,39 = 2.85; P = 0.036) showed that increased PIGD feature severity was associated with increased neocortical [11C]-Pittsburgh Compound B binding (β = 0.346; t39 = 2.13; P = 0.039) while controlling for striatal [11C]-dihydrotetrabenazine binding, age, and DRS total score. Increased neocortical β-amyloid deposition, even at low-range levels, is associated with higher PIGD feature severity in PD patients at risk for dementia. This finding may explain why the PIGD motor phenotype is a risk factor for the development of PDD. © 2012 Movement Disorder Society

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