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

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 [¹⁸F]FDOPA (for dopamine synthesis) and [¹¹C]NNC 112 (for D₁ receptors) PET scans and cognitive testing. Parametric images of [¹⁸F]FDOPA uptake (K_i) and [¹¹C]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 [¹⁸F]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 [¹⁸F]FDOPA uptake in PD difficult. We found no regional differences in D₁ receptor density between controls and PD, and no overall differences in frontostriatal performance. Although D₁ 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.