Frontal, midbrain and striatal dopaminergic function in early and advancedParkinson's disease A 3D [F-18]dopa-PET study

We have studied focal changes in dopaminergic function throughout the brain volume in early and advanced Parkinson's disease by applying statistical p arametric mapping (SPM) to 3D [F-18]dopa-PET. Data from seven early hemi-Pa rkinson's disease and seven advanced bilateral Parkinson's disease patients were compared with that from 12 normal controls. Parametric images of [F-1 8]dopa influx rate constant (K-i(o)) were generated for each subject from d ynamic 3D [F-18]dopa datasets and transformed into standard stereotactic sp ace. Significant changes in mean voxel [F-18]dopa K-i(o) values between the normal control group and each Parkinson's disease group were localized wit h SPM. Conventional region of interest analysis was also applied to compara ble regions on the untransformed image datasets. In early left hemi-Parkins on's disease, significant extrastriatal increases in [F-18]dopa K-i(o) were observed in the left anterior cingulate gyrus and the dorsal midbrain regi on (P < 0.05, corrected) along with decreases in striatal [F-18]dopa K-i(o) . In advanced Parkinson's disease, significant extrastriatal decreases in [ F-18]dopa K-i(o) were observed in the ventral and dorsal midbrain regions ( P < 0.05, corrected). No significant changes in [F-18]dopa K-i(o) were obse rved in the anterior cingulate region. In a direct comparison between the e arly and late Parkinson's disease groups, we observed relative [F-18]dopa K -i(o) reductions in ventral and dorsal midbrain, and dorsal pontine regions along with striatal [F-18]dopa K-i(o) reductions. Similiar results were fo und with a region of interest approach, on non-transformed data, except for the focal midbrain [F-18]dopa K-i(o) increase seen in early Parkinson's di sease. In conclusion, using SPM with [F-18]dopa-PET, we have objectively lo calized changes in extrastriatal, pre-synaptic dopaminergic function in Par kinson's disease. The significance of the increased dopaminergic activity o f anterior cingulate in early Parkinson's disease remains unclear, but may be compensatory. The [F-18]dopa signal in dorsal midbrain and pontine regio ns suggests that [F-18]dopa is taken up by serotonergic and noradrenergic n eurons which also degenerate in advanced Parkinson's disease. This suggests , therefore, that Parkinson's disease is a monoaminergic neurodegenerative disorder.