A1 Refereed original research article in a scientific journal
Extrastriatal dopamine D-2 receptors in Parkinson's disease: a longitudinal study
Authors: Kaasinen V, Aalto S, Nagren K, Hietala J, Sonninen P, Rinne JO
Publisher: SPRINGER-VERLAG WIEN
Publication year: 2003
Journal: Journal of Neural Transmission
Journal name in source: JOURNAL OF NEURAL TRANSMISSION
Journal acronym: J NEURAL TRANSM
Volume: 110
Issue: 6
First page : 591
Last page: 601
Number of pages: 11
ISSN: 0300-9564
DOI: https://doi.org/10.1007/s00702-003-0816-x
Abstract
Most antiparkinsonian drugs are known to act through central dopamine D-2 receptor agonism. A previous longitudinal positron emission tomography (PET) study has indicated that, in the striatum of Parkinson's disease (PD) patients, dopamine D-2 receptor binding declines at a relatively fast annual rate of 2-4% (compared to the rate of < 1%/year in healthy individuals). In the present study, the examination of longitudinal changes in D-2 receptors was extended to extrastriatal brain regions in PD. Eight early PD patients were examined twice with PET, similar to3 years apart, using a high-affinity extrastriatal D-2/D-3 receptor tracer, [C-11]FLB 457. Both the MRI-referenced region-of-interest method and the voxel-based statistical analysis method were used independently in the analysis. Regional D-2-like availabilities (binding potentials) in the left dorsolateral prefrontal cortex, the left temporal cortex and the left and right medial thalami were significantly decreased at the second examination by 20-37% (corresponding to an annual decline of 6-11%). Thus, the annual loss of extrastriatal D-2 availability in PD is up to three times faster than the rate previously reported in the putamen. Our longitudinal study shows first evidence concerning cortical D-2 receptor loss in the progression of PD, although it is not possible to distinguish between the effects of the therapy and the disease.
Most antiparkinsonian drugs are known to act through central dopamine D-2 receptor agonism. A previous longitudinal positron emission tomography (PET) study has indicated that, in the striatum of Parkinson's disease (PD) patients, dopamine D-2 receptor binding declines at a relatively fast annual rate of 2-4% (compared to the rate of < 1%/year in healthy individuals). In the present study, the examination of longitudinal changes in D-2 receptors was extended to extrastriatal brain regions in PD. Eight early PD patients were examined twice with PET, similar to3 years apart, using a high-affinity extrastriatal D-2/D-3 receptor tracer, [C-11]FLB 457. Both the MRI-referenced region-of-interest method and the voxel-based statistical analysis method were used independently in the analysis. Regional D-2-like availabilities (binding potentials) in the left dorsolateral prefrontal cortex, the left temporal cortex and the left and right medial thalami were significantly decreased at the second examination by 20-37% (corresponding to an annual decline of 6-11%). Thus, the annual loss of extrastriatal D-2 availability in PD is up to three times faster than the rate previously reported in the putamen. Our longitudinal study shows first evidence concerning cortical D-2 receptor loss in the progression of PD, although it is not possible to distinguish between the effects of the therapy and the disease.
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