[Evaluation of dopaminergic presynaptic function by [F-18] DOPA PET].

[F-18] fluorodopa ([F-18] DOPA) accumulates in the synaptic terminal of the dopaminergic neuron depending on the enzyme activity converting dopa into dopamine. The enzyme activity can be up/down-regulated by disease conditions, while the number of dopamine transporter is thought to be defined by the number of the synapse. There are four major pathways of dopaminergic projection systems. The nigrostriatal pathway is particularly involved in the production of movement, as part of a system called the basal ganglia motor loop. The mesocortila/ limbic pathway is be involved in cognitive function and motivation and emotional response. Dopaminergic functions in the extrastriatal area in addition to the striatum in vivo have been visualized with the combination of [F-18] DOPA PET and statistical image analyses. Ito K found the significant differences of influx rate (Ki) calculated with voxel-by-voxel Patlak analysis among Parkinson's disease (PD), PD with dementia (PDD), and normal control. Compared with the normal group, SPM localized declines of the [F-18] DOPA Ki bilaterally in the putamen, the right caudate nucleus and the left ventral midbrain for the PD group. Compared with the normal group, the PDD group showed reduced [F-18] DOPA Ki bilaterally in the striatum, midbrain and anterior cingulate. A relative difference in 18F-dopa uptake between PD and PDD was the bilateral decline in the anterior cingulate area and ventral striatum and in the right caudate nucleus in the PDD group. Accordingly, we conclude that dementia in PD is associated with impaired mesolimbic and caudate dopaminergic function. The next question is whether the corresponding dopaminergic change exists in the neural ganglia in the midbrain. We developed a method optimaized for the statistical analysis of the brain stem. PD showed slight increase of Ki in the raphe nucleus and the locus ceruleus. In contrast, PDD demonstrated decline tendency of Ki in the raphe and the locus ceruleus. These suggest cognitive impairment in PDD is caused by the affected the mesolimbic dopaminergic system which originates in the ventral tegmental area. This finding corresponds to Braak's staging of the intracerebral inclusion body pathology associated with PD.