Kato Takashi
Department of Brain Science and Molecular Imaging, National Center for Geriatrics and Gerontology.
Rinsho Shinkeigaku. 2007 Nov;47(11):829-31.
[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.
[F-18]氟多巴（[F-18] DOPA）根据将多巴转化为多巴胺的酶活性在多巴胺能神经元的突触末端积聚。酶活性可因疾病状态而上调或下调，而多巴胺转运体的数量被认为由突触数量决定。多巴胺能投射系统有四条主要通路。黑质纹状体通路作为基底神经节运动环路系统的一部分，尤其参与运动的产生。中脑皮质/边缘通路参与认知功能、动机和情绪反应。通过[F-18] DOPA正电子发射断层扫描（PET）与统计图像分析相结合，已在体内观察到纹状体以外的脑外区域的多巴胺能功能。伊藤·K发现，通过逐像素Patlak分析计算的帕金森病（PD）、帕金森病痴呆（PDD）和正常对照组之间的流入率（Ki）存在显著差异。与正常组相比，统计参数映射（SPM）显示PD组双侧壳核、右侧尾状核和左侧腹侧中脑的[F-18] DOPA Ki下降。与正常组相比，PDD组双侧纹状体、中脑和前扣带回的[F-18] DOPA Ki降低。PD和PDD之间18F-多巴摄取的相对差异在于PDD组前扣带回区域和腹侧纹状体以及右侧尾状核的双侧下降。因此，我们得出结论，PD中的痴呆与中脑边缘和尾状核多巴胺能功能受损有关。下一个问题是中脑的神经节中是否存在相应的多巴胺能变化。我们开发了一种针对脑干统计分析进行优化的方法。PD显示中缝核和蓝斑核的Ki略有增加。相比之下，PDD在中缝核和蓝斑核中显示出Ki下降的趋势。这些表明PDD中的认知障碍是由起源于腹侧被盖区的中脑边缘多巴胺能系统受影响所致。这一发现与与PD相关的脑内包涵体病理学的Braak分期相对应。
