Age-Specific Progression of Nigrostriatal Dysfunction in Parkinson's Disease
Age-Specific Progression of Nigrostriatal Dysfunction in Parkinson's Disease
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DOI：
10.1002/ana.22284
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发表时间：
2011-05-01
影响因子：
11.2
通讯作者：
Stoessl, A. Jon
中科院分区：
文献类型：
--
作者：
de la Fuente-Fernandez, Raul;Schulzer, Michael;Stoessl, A. Jon
目的：目的：探讨帕金森病（PD）患者黑质纹状体多巴胺功能障碍与年龄的关系。方法：对78例PD患者和35例健康对照者进行了正电子发射断层扫描（PET）研究，采用3种突触前多巴胺标记物：（1）[C-11]（+/-）二氢丁苯那嗪（DTBZ），测定囊泡单胺转运体2型密度;（2）[C-11]d-threo-methylphenidate，用于估计质膜多巴胺转运蛋白的密度;（3）6-[F-18]-fluoro-L-dopa，用于估计多巴脱羧酶的活性。在症状发作时，与老年PD患者相比，年轻患者的壳核DTBZ结合损失显著更大（p = 0.015）。然而，值得注意的是，DTBZ结合丢失的进展速度在年轻患者中明显较慢（p < 0.05）。估计的症状前阶段的疾病跨越超过20年的年轻患者，相比之下，1十年的老年patients.Interpretation：我们的研究结果表明，与老年患者相比，年轻的PD患者进展更慢，能够忍受更多的损害多巴胺能系统的第一个运动症状出现之前。这些观察结果表明，年轻的PD患者有更有效的代偿机制。神经网络2011; 69：803-810
Objective: To investigate in vivo the impact of age on nigrostriatal dopamine dysfunction in Parkinson's disease (PD).Methods: PD patients (n = 78) and healthy control subjects (n = 35) underwent longitudinal positron emission tomography assessments using 3 presynaptic dopamine markers: (1) [C-11](+/-)dihydrotetrabenazine (DTBZ), to estimate the density of the vesicular monoamine transporter type 2; (2) [C-11]d-threo-methylphenidate, to estimate the density of the plasma membrane dopamine transporter; and (3) 6-[F-18]-fluoro-L-dopa, to estimate the activity of the enzyme dopa-decarboxylase.Results: The study comprised 438 PD scans and 241 control scans (679 scans in total). At symptom onset, the loss of putamen DTBZ binding was substantially greater in younger compared to older PD patients (p = 0.015). Remarkably, however, the rate of progression of DTBZ binding loss was significantly slower in younger patients (p < 0.05). The estimated presymptomatic phase of the disease spanned more than 2 decades in younger patients, compared to 1 decade in older patients.Interpretation: Our results suggest that, compared to older patients, younger PD patients progress more slowly and are able to endure more damage to the dopaminergic system before the first motor symptoms appear. These observations suggest that younger PD patients have more efficient compensatory mechanisms. ANN NEUROL 2011; 69: 803-810