Longitudinal evolution of compensatory changes in striatal dopamine processing in Parkinson's disease

Ramachandiran Nandhagopal, Lisa Kuramoto, Michael Schulzer, Edwin Mak, Jacqueline Cragg, Jess McKenzie, Siobhan McCormick, Thomas J. Ruth, Vesna Sossi, Raul De La Fuente-Fernandez, A. Jon Stoessl

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Abstract

Parkinson's disease is a relentlessly progressive neurodegenerative disease. Breakdown of compensatory mechanisms influencing putaminal dopamine processing could contribute to the progressive motor symptoms. We studied a cohort of 78 subjects (at baseline) with sporadic Parkinson's disease and 35 healthy controls with multi-tracer positron emission tomography scans to investigate the evolution of adaptive mechanisms influencing striatal dopamine processing in Parkinson's disease progression. Presynaptic dopaminergic integrity was assessed with three radioligands: (i) [11C](±) dihydrotetrabenazine, to estimate the density of vesicular monoamine transporter type 2; (ii) [11C]d-threo-methylphenidate, to label the dopamine transporter; and (iii) 6-[18F]fluoro-l-DOPA, to assess the activity of aromatic amino acid decarboxylase and storage of 6-[18F]- fluorodopamine in synaptic vesicles. The subjects with Parkinson's disease and the healthy controls underwent positron emission tomography scans at the initial visit and after 4 and 8 years of follow-up. Non-linear multivariate regression analyses with random effects were utilized to model the longitudinal changes in tracer values in the putamen standardized relative to normal controls. We found evidence for possible upregulation of dopamine synthesis and downregulation of dopamine transporter in the more severely affected putamen in the early stage of Parkinson's disease. The standardized 6-[18F]fluoro-l-DOPA and [11C]d-threo-methylphenidate values tended to approach [ 11C](±)dihydrotetrabenazine values in the putamen in later stages of disease (i.e. for [11C](±)dihydrotetrabenazine values

Original languageEnglish
Pages (from-to)3290-3298
Number of pages9
JournalBrain
Volume134
Issue number11
DOIs
Publication statusPublished - 2011

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Keywords

  • compensatory changes
  • motor dysfunction
  • Parkinson's disease
  • PET
  • striatal dopamine processing

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Nandhagopal, R., Kuramoto, L., Schulzer, M., Mak, E., Cragg, J., McKenzie, J., ... Stoessl, A. J. (2011). Longitudinal evolution of compensatory changes in striatal dopamine processing in Parkinson's disease. Brain, 134(11), 3290-3298. https://doi.org/10.1093/brain/awr233