Bohnen N I, Müller M L T M, Koeppe R A, Studenski S A, Kilbourn M A, Frey K A, Albin R L
Department of Radiology, Division of Nuclear Medicine, University of Michigan, Ann Arbor 48105-9755, USA.
Neurology. 2009 Nov 17;73(20):1670-6. doi: 10.1212/WNL.0b013e3181c1ded6.
To investigate the relationships between history of falls and cholinergic vs dopaminergic denervation in patients with Parkinson disease (PD).
There is a need to explore nondopaminergic mechanisms of gait control as the majority of motor impairments associated with falls in PD are resistant to dopaminergic treatment. Alterations in cholinergic neurotransmission in PD may be implicated because of evidence that gait control depends on cholinergic system-mediated higher-level cortical and subcortical processing, including pedunculopontine nucleus (PPN) function.
In this cross-sectional study, 44 patients with PD (Hoehn & Yahr stages I-III) without dementia and 15 control subjects underwent a clinical assessment and [(11)C]methyl-4-piperidinyl propionate (PMP) acetylcholinesterase (AChE) and [(11)C]dihydrotetrabenazine (DTBZ) vesicular monoamine transporter type 2 (VMAT2) brain PET imaging.
Seventeen patients (38.6%) reported a history of falls and 27 patients had no falls. Analysis of covariance of the cortical AChE hydrolysis rates demonstrated reduced cortical AChE in the PD fallers group (-12.3%) followed by the PD nonfallers (-6.6%) compared to control subjects (F = 7.22, p = 0.0004). Thalamic AChE activity was lower only in the PD fallers group (-11.8%; F = 4.36, p = 0.008). There was no significant difference in nigrostriatal dopaminergic activity between PD fallers and nonfallers.
Unlike nigrostriatal dopaminergic denervation, cholinergic hypofunction is associated with fall status in Parkinson disease (PD). Thalamic AChE activity in part represents cholinergic output of the pedunculopontine nucleus (PPN), a key node for gait control. Our results are consistent with other data indicating that PPN degeneration is a major factor leading to impaired postural control and gait dysfunction in PD.
探讨帕金森病（PD）患者跌倒史与胆碱能和多巴胺能去神经支配之间的关系。
由于与PD跌倒相关的大多数运动障碍对多巴胺能治疗有抵抗性，因此有必要探索步态控制的非多巴胺能机制。PD中胆碱能神经传递的改变可能与之有关，因为有证据表明步态控制依赖于胆碱能系统介导的高级皮质和皮质下加工，包括脚桥核（PPN）功能。
在这项横断面研究中，44例无痴呆的PD患者（Hoehn & Yahr分期I-III）和15名对照受试者接受了临床评估以及[（11）C]甲基-4-哌啶丙酸酯（PMP）乙酰胆碱酯酶（AChE）和[（11）C]二氢丁苯那嗪（DTBZ）囊泡单胺转运体2（VMAT2）脑PET成像。
17例患者（38.6%）报告有跌倒史，27例患者无跌倒史。对皮质AChE水解率的协方差分析表明，与对照受试者相比，PD跌倒者组的皮质AChE降低（-12.3%），其次是PD未跌倒者组（-6.6%）（F = 7.22，p = 0.0004）。仅PD跌倒者组的丘脑AChE活性较低（-11.8%；F = 4.36，p = 0.008）。PD跌倒者和未跌倒者之间黑质纹状体多巴胺能活性无显著差异。
与黑质纹状体多巴胺能去神经支配不同，胆碱能功能减退与帕金森病（PD）的跌倒状态相关。丘脑AChE活性部分代表脚桥核（PPN）的胆碱能输出，PPN是步态控制的关键节点。我们的结果与其他数据一致，表明PPN变性是导致PD姿势控制受损和步态功能障碍的主要因素。
