Extrastriatal dopamine D2 receptors in Parkinson's disease: a longitudinal study
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Most antiparkinsonian drugs are known to act through central dopamine D2 receptor agonism. A previous longitudinal positron emission tomography (PET) study has indicated that, in the striatum of Parkinson's disease (PD) patients, dopamine D2 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 D2 receptors was extended to extrastriatal brain regions in PD. Eight early PD patients were examined twice with PET, ∼3 years apart, using a high-affinity extrastriatal D2/D3 receptor tracer, [11C]FLB 457. Both the MRI-referenced region-of-interest method and the voxel-based statistical analysis method were used independently in the analysis. Regional D2-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 D2 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 D2 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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