Increased frontal [F-18]fluorodopa uptake in early Parkinson's Disease: sex differences in the prefrontal cortex

Previous imaging studies in Parkinson's disease have focused mainly on the striatum, a region with very high dopaminergic activity, Using modern high- sensitivity 3D [F-18]fluorodopa (Fdopa)-PET, mesocortical monoamine project ions can be studied. To study the frontal monoaminergic system in unmedicat ed early Parkinson's disease in vivo, we examined 20 early Parkinson's dise ase patients (10 women, 10 men) and 16 healthy subjects (nine women, seven men) with 3D Fdopa-PET, using standard region-of-interest-based analysis wi th MRI co-registration. Women with Parkinson's disease had 87% higher Fdopa uptake in the right dorsolateral prefrontal cortex (area 46) compared with men with Parkinson's disease, whereas there was no sex difference in the c ontrol group (sex x disease interaction, P = 0.03), The uptake in the right dorsolateral prefrontal cortex was 82% higher in men with Parkinson's dise ase and 219% higher in women with Parkinson's disease compared with control groups (effect of disease, P < 0.0001), Also in the left dorsolateral pref rontal cortex and in the medial frontal cortex, early Parkinson's disease p atients had significantly (18-94%) higher Fdopa uptake compared with health y controls. In the putamen, both men and women with Parkinson's disease had a significantly lower (27-46%) uptake compared with healthy controls. Thes e results indicate that frontal monoaminergic activity is increased and tha t there is a sex difference in the prefrontal monoaminergic system in early Parkinson's disease, The reported sex difference may be linked to clinical sex differences in the symptoms and treatment response in Parkinson's dise ase.