Skip Navigation


Brain Advance Access originally published online on August 18, 2009
Brain 2009 132(11):2970-2979; doi:10.1093/brain/awp209
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
132/11/2970    most recent
awp209v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Nandhagopal, R.
Right arrow Articles by Stoessl, A. J.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nandhagopal, R.
Right arrow Articles by Stoessl, A. J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author (2009). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Longitudinal progression of sporadic Parkinson's disease: a multi-tracer positron emission tomography study

R. Nandhagopal1, L. Kuramoto1, M. Schulzer1, E. Mak1, J. Cragg1, Chong S. Lee1, J. McKenzie1, S. McCormick1, A. Samii2, A. Troiano1, T. J. Ruth3, V. Sossi4, R. de la Fuente-Fernandez1, Donald B. Calne1 and A. J. Stoessl1

1 Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC V6T2B5 Canada 2 Department of Neurology, University of Washington, Seattle, WA 98195 USA 3 TRIUMF, Wesbrook Mall, Vancouver, BC V6T 2A3 Canada 4 Department of Physics & Astronomy, University of British Columbia, Vancouver Hospital and Health Sciences Centre, Purdy Pavilion, Vancouver, BC V6T2B5 Canada

Correspondence to: A. Jon Stoessl, CM, MD, FRCPC, Pacific Parkinson's Research Centre, University of British Columbia, Vancouver Hospital and Health Sciences Centre, Purdy Pavilion, 2221 Wesbrook Mall, Vancouver, BC, V6T2B5 Canada E-mail: jstoessl{at}interchange.ubc.ca

Parkinson's disease is a heterogeneous disorder with multiple factors contributing to disease initiation and progression. Using serial, multi-tracer positron emission tomography imaging, we studied a cohort of 78 subjects with sporadic Parkinson's disease to understand the disease course better. Subjects were scanned with radiotracers of presynaptic dopaminergic integrity at baseline and again after 4 and 8 years of follow-up. Non-linear multivariate regression analyses, using random effects, of the form BPND(t) or Kocc(t) = a*e(–bt–dA) + c, where BPND = tracer binding potential (nondispaceable), KOCC = tracer uptake constant a, b, c and d are regression parameters, t is the symptom duration and A is the age at onset, were utilized to model the longitudinal progression of radiotracer binding/uptake. We found that the initial tracer binding/uptake was significantly different in anterior versus posterior striatal subregions, indicating that the degree of denervation at disease onset was different between regions. However, the relative rate of decline in tracer binding/uptake was similar between the striatal subregions. While an antero-posterior gradient of severity was maintained for dopamine synthesis, storage and reuptake, the asymmetry between the more and less affected striatum became less prominent over the disease course. Our study suggests that the mechanisms underlying Parkinson's disease initiation and progression are probably different. Whereas factors responsible for disease initiation affect striatal subregions differently, those factors contributing to disease progression affect all striatal subregions to a similar degree and may therefore reflect non-specific mechanisms such as oxidative stress, inflammation or excitotoxicity.

Key Words: Parkinson's disease; PET; progression; asymmetry; dopaminergic dysfunction

Abbreviations: DA, dopamine; DAT, membrane dopamine transporter; DTBZ, dihydrotetrabenazine; FD, fluoro-L-dopa; MP, methylphenidate; PET, positron emission tomography; ROIs, regions of interest

Received January 24, 2009. Revised May 20, 2009. Accepted June 26, 2009.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.