Extrastriatal dopamine D₂ receptors in Parkinson's disease: a longitudinal study

Summary.

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.