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.

Full 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.

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Author information

Author/s: Cropley, Vanessa L (VL); Fujita, Masahiro (M); Bara-Jimenez, William (W); Brown, Amira K (AK); Zhang, Xiang-Yang (XY); Sangare, Janet (J); Herscovitch, Peter (P); Pike, Victor W (VW); Hallett, Mark (M); Nathan, Pradeep J (PJ); Innis, Robert B (RB);

Affiliation: Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-0135, USA. vcropley(-atsign-)groupwise.swin.edu.au

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Intramural

Journal: Psychiatry research (Psychiatry Res), published in Ireland. (Language: eng)

Reference: 2008-Jul; vol 163 (issue 2) : pp 171-82

Dates: Created 2008/06/09; Completed 2008/08/22;

PMID: 18504119, status: MEDLINE (last retrieval date: 11/6/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Attention - physiology
Benzazepines - diagnostic use
Benzofurans - diagnostic use
Brain Mapping
Carbon Radioisotopes - diagnostic use
Cognition Disorders - physiopathology; radionuclide imaging
Color Perception - physiology
Corpus Striatum - physiopathology; radionuclide imaging
Dihydroxyphenylalanine - analogs & derivatives; diagnostic use
Discrimination Learning - physiology
Dopamine - metabolism
Fluorine Radioisotopes - diagnostic use
Frontal Lobe - physiopathology; radionuclide imaging
Humans

Humans
Image Processing, Computer-Assisted
Magnetic Resonance Imaging
Mental Status Schedule
Nerve Net - physiopathology; radionuclide imaging
Neuropsychological Tests
Parkinson Disease - physiopathology; radionuclide imaging
Pattern Recognition, Visual - physiology
Positron-Emission Tomography
Presynaptic Terminals - physiology; radionuclide imaging
Problem Solving - physiology
Psychomotor Performance - physiology
Receptors, Dopamine D1 - metabolism
Synaptic Membranes - physiology; radionuclide imaging

Associated Chemicals: Benzazepines (0) ; Benzofurans (0) ; Carbon Radioisotopes (0) ; Fluorine Radioisotopes (0) ; Receptors, Dopamine D1 (0) ; NNC 112 (125341-24-4) ; Dopamine (51-61-6) ; Dihydroxyphenylalanine (63-84-3) ; fluorodopa F 18 (75290-51-6)

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