Progression of monoaminergic dysfunction in Parkinson's disease: A longitudinal 18F-dopa PET study
Progression of monoaminergic dysfunction in Parkinson's disease: A longitudinal 18F-dopa PET study
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DOI：
10.1016/j.neuroimage.2011.03.012
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发表时间：
2011-06-01
期刊：
影响因子：
5.7
通讯作者：
Brooks, David J.
中科院分区：
文献类型：
--
作者：
Pavese, Nicola;Rivero-Bosch, Maria;Brooks, David J.
帕金森病（PD）的尸检和神经影像学研究表明，与黑质纹状体多巴胺神经元的特征性变性有关的脑血清素能、去甲肾上腺素能和胆碱能通路。这些肋外区退行性过程的进展速度尚不清楚。我们使用F-18-dopa PET（单胺能神经元中芳香氨基酸脱羧酶活性的标记物）来评估一组早期PD患者在3年内脑去甲肾上腺素能、血清素能和脑外多巴胺能结构中示踪剂摄取的纵向变化。10例PD患者在基线和37.1 +/- 21.5个月随访后进行两次f -18-多巴PET检查。使用标准目标图提取11个纹状体和纹状体外区域的示踪剂内流常数（Ki）。在随访期间，大多数研究区域的f -18多巴胺含量都出现了渐进式下降，壳核（8.1%）、蓝斑（7.8%）和内白球（7.7%）的年下降速度最快。尾状体和下丘脑Ki的年降幅分别为6.3%和6.1%。在基线时，PD中一些结构的f -18多巴摄取水平比对照组（内部苍白球、蓝斑）有所增加，表明可能存在单胺转换的代偿性上调。这些增加的水平在随访中已正常化（内部苍白球）或变为亚正常（蓝斑），表明这些机制在疾病的头几年耗尽。正如f -18多巴PET所反映的那样，纹状体外区单胺功能的丧失是延迟的，并且与黑质纹状体变性无关。评估新型神经保护剂对帕金森病黑质纹状体功能障碍的疗效。F-18-dopa PET可提供有关胃外单胺能结构功能的补充信息。(C) 2011爱思唯尔公司版权所有。
Post-mortem and neuroimaging studies in Parkinson's disease (PD) have shown involvement of the brain serotoninergic, noradrenergic and cholinergic pathways alongside the characteristic degeneration of nigrostriatal dopamine neurons. The rate of progression of the degenerative process in these extrastriatal areas is still unclear.We used F-18-dopa PET, a marker of aromatic aminoacid decarboxylase activity in monoaminergic neurons, to assess longitudinal changes in tracer uptake in brain noradrenergic, serotoninergic and extrastriatal dopaminergic structures over a 3-year period in a group of early PD patients.Ten PD patients had F-18-dopa PET twice: at baseline and again after 37.1 +/- 21.5 months follow up. A standard object map was used to extract tracer influx constants (Ki) in 11 striatal and extrastriatal regions. Progressive decreases in F-18-dopa Ki occurred over the follow-up period in the majority of the investigated areas, the fastest annual declines occurring in putamen (8.1%), locus coeruleus (7.8%), and globus pallidus interna (7.7%). Caudate and hypothalamus showed 6.3% and 6.1% annual Ki declines, respectively. At baseline, some structures showed increased levels of F-18-dopa uptake in PD compared to controls (internal pallidum, locus coeruleus), indicating possible compensatory upregulation of monoamine turnover. These increased levels had normalised (globus pallidus interna) or become subnormal (locus coeruleus) at follow-up suggesting exhaustion of these mechanisms within the first years of disease.Loss of monoaminergic function in extrastriatal regions, as reflected by F-18-dopa PET, is delayed and occurs independently from nigrostriatal degeneration. When assessing the efficacy of novel neuroprotective agents on nigrostriatal dysfunction in PD. F-18-dopa PET could provide supplementary information concerning function of extrastriatal monoaminergic structures. (C) 2011 Elsevier Inc. All rights reserved.