Pre- and post-synaptic dopamine imaging and its relation with frontostriatal cognitive function in Parkinson disease: PET studies with [11C]NNC 112 and [18F]FDOPA

Vanessa L. Cropley, Masahiro Fujita, William Bara-Jimenez, Amira K. Brown, Xiang Yang Zhang, Janet Sangare, Peter Herscovitch, Victor W. Pike, Mark Hallett, Pradeep J. Nathan, Robert B. Innis

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

Frontostriatal cognitive dysfunction is common in Parkinson disease (PD), but the explanation for its heterogeneous expressions remains unclear. This study examined the dopamine system within the frontostriatal circuitry with positron emission tomography (PET) to investigate pre- and post-synaptic dopamine function in relation to the executive processes in PD. Fifteen non-demented PD patients and 14 healthy controls underwent [18F]FDOPA (for dopamine synthesis) and [11C]NNC 112 (for D1 receptors) PET scans and cognitive testing. Parametric images of [18F]FDOPA uptake (Ki) and [11C]NNC 112 binding potential (BPND) were calculated using reference tissue models. Group differences in Ki and BPND were assessed with both volume of interest and statistical parametric mapping, and were correlated with cognitive tests. Measurement of [18F]FDOPA uptake in cerebral cortex was questionable because of higher Ki values in white than adjacent gray matter. These paradoxical results were likely to be caused by violations of the reference tissue model assumption rendering interpretation of cortical [18F]FDOPA uptake in PD difficult. We found no regional differences in D1 receptor density between controls and PD, and no overall differences in frontostriatal performance. Although D1 receptor density did not relate to frontostriatal cognition, Ki decreases in the putamen predicted performance on the Wisconsin Card Sorting Test in PD only. These results suggest that striatal dopamine denervation may contribute to some frontostriatal cognitive impairment in moderate stage PD.

Original languageEnglish (US)
Pages (from-to)171-182
Number of pages12
JournalPsychiatry Research - Neuroimaging
Volume163
Issue number2
DOIs
StatePublished - Jul 15 2008

Keywords

  • Dopamine
  • Frontostriatal cognition
  • PET
  • Parkinson disease
  • [C]NNC 112
  • [F]FDOPA

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Radiology Nuclear Medicine and imaging
  • Psychiatry and Mental health

Fingerprint Dive into the research topics of 'Pre- and post-synaptic dopamine imaging and its relation with frontostriatal cognitive function in Parkinson disease: PET studies with [<sup>11</sup>C]NNC 112 and [<sup>18</sup>F]FDOPA'. Together they form a unique fingerprint.

Cite this