title: 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.
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 [(18)F]FDOPA (for dopamine synthesis) and [(11)C]NNC 112 (for D(1) receptors) PET scans and cognitive testing. Parametric images of [(18)F]FDOPA uptake (K(i)) and [(11)C]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 [(18)F]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 [(18)F]FDOPA uptake in PD difficult. We found no regional differences in D(1) receptor density between controls and PD, and no overall differences in frontostriatal performance. Although D(1) 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.
authors.affiliation: Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-0135, USA. vcropley@groupwise.swin.edu.au
authors.forename: Vanessa L
authors.initials: VL
authors.lastname: Cropley
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fujita
authors.forename: William
authors.initials: W
authors.lastname: Bara-Jimenez
authors.forename: Amira K
authors.initials: AK
authors.lastname: Brown
authors.forename: Xiang-Yang
authors.initials: XY
authors.lastname: Zhang
authors.forename: Janet
authors.initials: J
authors.lastname: Sangare
authors.forename: Peter
authors.initials: P
authors.lastname: Herscovitch
authors.forename: Victor W
authors.initials: VW
authors.lastname: Pike
authors.forename: Mark
authors.initials: M
authors.lastname: Hallett
authors.forename: Pradeep J
authors.initials: PJ
authors.lastname: Nathan
authors.forename: Robert B
authors.initials: RB
authors.lastname: Innis
mesh_terms: D001288:Attention / Q000502:physiology; D001552:Benzazepines; D001572:Benzofurans; D001931:Brain Mapping; D002250:Carbon Radioisotopes; D003072:Cognition Disorders / Q000000981:diagnostic imaging* / Q000503:physiopathology; D003118:Color Perception / Q000502:physiology; D003342:Corpus Striatum / Q000000981:diagnostic imaging* / Q000503:physiopathology; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives; D004193:Discrimination Learning / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D005462:Fluorine Radioisotopes; D005625:Frontal Lobe / Q000000981:diagnostic imaging* / Q000503:physiopathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008609:Mental Status Schedule; D009415:Nerve Net / Q000000981:diagnostic imaging / Q000503:physiopathology; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000000981:diagnostic imaging* / Q000503:physiopathology; D010364:Pattern Recognition, Visual / Q000502:physiology; D049268:Positron-Emission Tomography; D017729:Presynaptic Terminals / Q000000981:diagnostic imaging* / Q000502:physiology; D011340:Problem Solving / Q000502:physiology; D011597:Psychomotor Performance / Q000502:physiology; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D013570:Synaptic Membranes / Q000000981:diagnostic imaging* / Q000502:physiology
chemical_list: D001552:Benzazepines; D001572:Benzofurans; D002250:Carbon Radioisotopes; D005462:Fluorine Radioisotopes; D017447:Receptors, Dopamine D1; C077123:NNC 112; C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine; D004298:Dopamine