Bohnen Nicolaas I, Frey Kirk A, Studenski Stephanie, Kotagal Vikas, Koeppe Robert A, Constantine Gregory M, Scott Peter J H, Albin Roger L, Müller Martijn L T M
Department of Radiology, Division of Nuclear Medicine, University of Michigan, Ann Arbor, MI, USA; Department of Neurology, University of Michigan, Ann Arbor, MI, USA; Neurology Service and GRECC, VAAAHS, Ann Arbor, MI, USA.
Mov Disord. 2014 Aug;29(9):1118-24. doi: 10.1002/mds.25929. Epub 2014 Jun 7.
Cholinergic denervation has been associated with falls and slower gait speed and β-amyloid deposition with greater severity of axial motor impairments in Parkinson disease (PD). However, little is known about the association between the presence of extra-nigral pathological conditions and freezing of gait (FoG). Patients with PD (n = 143; age, 65.5 ± 7.4 years, Hoehn and Yahr stage, 2.4 ± 0.6; Montreal Cognitive Assessment score, 25.9 ± 2.6) underwent [(11) C]methyl-4-piperidinyl propionate acetylcholinesterase and [(11) C]dihydrotetrabenazine dopaminergic PET imaging, and clinical, including FoG, assessment in the dopaminergic "off" state. A subset of subjects (n = 61) underwent [(11) C]Pittsburgh compound-B β-amyloid positron emission tomography (PET) imaging. Normative data were used to dichotomize abnormal β-amyloid uptake or cholinergic deficits. Freezing of gait was present in 20 patients (14.0%). Freezers had longer duration of disease (P = 0.009), more severe motor disease (P < 0.0001), and lower striatal dopaminergic activity (P = 0.013) compared with non-freezers. Freezing of gait was more common in patients with diminished neocortical cholinergic innervation (23.9%, χ(2) = 5.56, P = 0.018), but not in the thalamic cholinergic denervation group (17.4%, χ(2) = 0.26, P = 0.61). Subgroup analysis showed higher frequency of FoG with increased neocortical β-amyloid deposition (30.4%, Fisher Exact test: P = 0.032). Frequency of FoG was lowest with absence of both pathological conditions (4.8%), intermediate in subjects with single extra-nigral pathological condition (14.3%), and highest with combined neocortical cholinopathy and amyloidopathy (41.7%; Cochran-Armitage trend test, Z = 2.63, P = 0.015). Within the group of freezers, 90% had at least one of the two extra-nigral pathological conditions studied. Extra-nigral pathological conditions, in particular the combined presence of cortical cholinopathy and amyloidopathy, are common in PD with FoG and may contribute to its pathophysiology. © 2014 International Parkinson and Movement Disorder Society.
胆碱能去神经支配与帕金森病（PD）患者的跌倒和步态速度减慢有关，而β-淀粉样蛋白沉积与轴性运动障碍的严重程度增加有关。然而，关于黑质外病理状况与步态冻结（FoG）之间的关联知之甚少。对143例PD患者（年龄65.5±7.4岁，Hoehn和Yahr分期2.4±0.6；蒙特利尔认知评估得分25.9±2.6）进行了[（11）C]甲基-4-哌啶基丙酸酯乙酰胆碱酯酶和[（11）C]二氢丁苯那嗪多巴胺能PET成像，并在多巴胺能“关”状态下进行了包括FoG在内的临床评估。一部分受试者（n = 61）进行了[（11）C]匹兹堡化合物-Bβ-淀粉样蛋白正电子发射断层扫描（PET）成像。使用正常数据将异常的β-淀粉样蛋白摄取或胆碱能缺陷进行二分法分类。20例患者（14.0%）存在步态冻结。与非步态冻结者相比，步态冻结者的病程更长（P = 0.009），运动疾病更严重（P < 0.0001），纹状体多巴胺能活性更低（P = 0.013）。步态冻结在新皮质胆碱能神经支配减少的患者中更常见（23.9%，χ（2）= 5.56，P = 0.018），但在丘脑胆碱能去神经支配组中并不常见（17.4%，χ（2）= 0.26，P = 0.61）。亚组分析显示，随着新皮质β-淀粉样蛋白沉积增加，FoG的发生率更高（30.4%，Fisher精确检验：P = 0.032）。在两种病理状况均不存在的情况下，FoG的发生率最低（4.8%），在存在单一黑质外病理状况的受试者中为中等（14.3%），而在合并新皮质胆碱病和淀粉样变性的情况下最高（41.7%； Cochr an-Armitage趋势检验，Z = 2.63，P = 0.015）。在步态冻结组中，9
