Longitudinal progression of sporadic Parkinson's disease

A multi-tracer positron emission tomography study

R. Nandhagopal, L. Kuramoto, M. Schulzer, E. Mak, J. Cragg, Chong S. Lee, J. McKenzie, S. McCormick, A. Samii, A. Troiano, T. J. Ruth, V. Sossi, R. De La Fuente-Fernandez, Donald B. Calne, A. J. Stoessl

Research output: Contribution to journalArticle

141 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2970-2979
Number of pages10
JournalBrain
Volume132
Issue number11
DOIs
Publication statusPublished - Nov 2009

Fingerprint

Corpus Striatum
Positron-Emission Tomography
Parkinson Disease
Disease Progression
Denervation
Age of Onset
Dopamine
Oxidative Stress
Multivariate Analysis
Regression Analysis
Inflammation

Keywords

  • Asymmetry
  • Dopaminergic dysfunction
  • Parkinson's disease
  • PET
  • Progression

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Nandhagopal, R., Kuramoto, L., Schulzer, M., Mak, E., Cragg, J., Lee, C. S., ... Stoessl, A. J. (2009). Longitudinal progression of sporadic Parkinson's disease: A multi-tracer positron emission tomography study. Brain, 132(11), 2970-2979. https://doi.org/10.1093/brain/awp209

Longitudinal progression of sporadic Parkinson's disease : A multi-tracer positron emission tomography study. / Nandhagopal, R.; Kuramoto, L.; Schulzer, M.; Mak, E.; Cragg, J.; Lee, Chong S.; McKenzie, J.; McCormick, S.; Samii, A.; Troiano, A.; Ruth, T. J.; Sossi, V.; De La Fuente-Fernandez, R.; Calne, Donald B.; Stoessl, A. J.

In: Brain, Vol. 132, No. 11, 11.2009, p. 2970-2979.

Research output: Contribution to journalArticle

Nandhagopal, R, Kuramoto, L, Schulzer, M, Mak, E, Cragg, J, Lee, CS, McKenzie, J, McCormick, S, Samii, A, Troiano, A, Ruth, TJ, Sossi, V, De La Fuente-Fernandez, R, Calne, DB & Stoessl, AJ 2009, 'Longitudinal progression of sporadic Parkinson's disease: A multi-tracer positron emission tomography study', Brain, vol. 132, no. 11, pp. 2970-2979. https://doi.org/10.1093/brain/awp209
Nandhagopal, R. ; Kuramoto, L. ; Schulzer, M. ; Mak, E. ; Cragg, J. ; Lee, Chong S. ; McKenzie, J. ; McCormick, S. ; Samii, A. ; Troiano, A. ; Ruth, T. J. ; Sossi, V. ; De La Fuente-Fernandez, R. ; Calne, Donald B. ; Stoessl, A. J. / Longitudinal progression of sporadic Parkinson's disease : A multi-tracer positron emission tomography study. In: Brain. 2009 ; Vol. 132, No. 11. pp. 2970-2979.
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