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

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

doi:10.1016/j.pscychresns.2007.11.003

« Previous Next »Psychiatry Research: Neuroimaging
Volume 163, Issue 2 , Pages 171-182, 15 July 2008

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
- Molecular Imaging Branch, National Institute of Mental Health, Bethesda, MD, USA
- Brain Sciences Institute, Swinburne University of Technology, Hawthorn, Victoria, Australia
- Corresponding authors. National Institute of Mental Health, National Institutes of Health, Bldg. 31, Rm. B2-B37, 1 Center Drive, MSC 0135, Bethesda, MD 20892-0135, USA. Tel.: +301 594 1368; fax: +301 480 3610.
Masahiro Fujita
- Molecular Imaging Branch, National Institute of Mental Health, Bethesda, MD, USA
William Bara-Jimenez
- Human Motor Control Section, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA
Amira K. Brown
- Molecular Imaging Branch, National Institute of Mental Health, Bethesda, MD, USA
Xiang-Yang Zhang
- Molecular Imaging Branch, National Institute of Mental Health, Bethesda, MD, USA
Janet Sangare
- Molecular Imaging Branch, National Institute of Mental Health, Bethesda, MD, USA
Peter Herscovitch
- PET Department, Clinical Center, National Institutes of Health, Bethesda, MD, USA
Victor W. Pike
- Molecular Imaging Branch, National Institute of Mental Health, Bethesda, MD, USA
Mark Hallett
- Human Motor Control Section, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA
Pradeep J. Nathan
- School of Psychology, Psychiatry and Psychological Medicine, Monash University, Clayton, Victoria, Australia
Robert B. Innis
- Molecular Imaging Branch, National Institute of Mental Health, Bethesda, MD, USA
- Corresponding authors. National Institute of Mental Health, National Institutes of Health, Bldg. 31, Rm. B2-B37, 1 Center Drive, MSC 0135, Bethesda, MD 20892-0135, USA. Tel.: +301 594 1368; fax: +301 480 3610.

Received 15 August 2007; received in revised form 12 November 2007; accepted 14 November 2007.

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 (K_i) and [¹¹C]NNC 112 binding potential (BP_ND) were calculated using reference tissue models. Group differences in K_i and BP_ND 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 K_i 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, K_i 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.