Gait variability is linked to the atrophy of the Nucleus Basalis of Meynert and is resistant to STN DBS in Parkinson's disease.
Gait variability is linked to the atrophy of the Nucleus Basalis of Meynert and is resistant to STN DBS in Parkinson's disease.
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DOI：
10.1016/j.nbd.2020.105134
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发表时间：
2020-12
影响因子：
6.1
通讯作者：
Bronte-Stewart HM
中科院分区：
文献类型：
--
作者：
Wilkins KB;Parker JE;Bronte-Stewart HM
帕金森病（PD）是一种全身性脑疾病，其中皮质胆碱能网络在疾病过程的早期开始退化。皮质胆碱能网络缺乏容易获得的、定量的和特异性的行为标记物。虽然多巴胺能网络的退化可能是主要运动体征缺陷的原因，但步态的控制是一个复杂的过程，并且步态的高阶方面（如步态变异性）的控制可能受到胆碱能网络认知过程的影响。我们研究了摆动时间变异性，步态变异性的度量，是独立于步态速度，是一个定量的行为标记的皮质胆碱能网络的完整性在PD。22名接受PD和丘脑底核（DBS）脑深部电刺激的个体（PD-DBS队列）和29名年龄匹配的对照者进行了经验证的原地踏步（SIP）任务，以评估所有治疗的摆动时间变异性。PD-DBS队列接受了结构MRI扫描，以测量Meynert基底核（NBM）的灰质体积，NBM是皮质胆碱能网络中的关键节点。为了确定多巴胺能系统对挥杆时间变异性的作用，在PD-DBS队列中测量了开启和关闭DBS，并在第二个32人的PD队列（PD-med）中测量了开启和关闭多巴胺能药物。PD-DBS队列中的11名患者在连续DBS治疗3年后再次完成了SIP任务，以评估步态障碍的进展。摆动时间变异性显著更大（即，与对照组相比，PD患者的摆动时间变异性更大，与步态速度一样，摆动时间变异性与NBM萎缩程度更大相关。DBS显著改善了主要运动体征和步态速度，但没有改善摆动时间变异性，这在使用多巴胺能药物的第二个队列中得到了复制。在连续三年的DBS治疗后，PD患者的摆动时间变异性继续恶化，NBM萎缩显示出预测增加程度的趋势。相反，主要运动体征没有进展。这些结果表明，摆动时间的变异性是一个可靠的标记皮质胆碱能健康，并支持一个框架，其中高阶方面的步态控制在PD依赖于皮质胆碱能系统，相比之下，其他运动方面的PD依赖于多巴胺能网络。
Parkinson’s disease (PD) is a systemic brain disorder where the cortical cholinergic network begins to degenerate early in the disease process. Readily accessible, quantitative, and specific behavioral markers of the cortical cholinergic network are lacking. Although degeneration of the dopaminergic network may be responsible for deficits in cardinal motor signs, the control of gait is a complex process and control of higher-order aspects of gait, such as gait variability, may be influenced by cognitive processes attributed to cholinergic networks. We investigated whether swing time variability, a metric of gait variability that is independent from gait speed, was a quantitative behavioral marker of cortical cholinergic network integrity in PD. Twenty-two individuals with PD and subthalamic nucleus (STN) deep brain stimulation (PD-DBS cohort) and twenty-nine age-matched controls performed a validated stepping-in-place (SIP) task to assess swing time variability off all therapy. The PD-DBS cohort underwent structural MRI scans to measure gray matter volume of the Nucleus Basalis of Meynert (NBM), the key node in the cortical cholinergic network. In order to determine the role of the dopaminergic system on swing time variability, it was measured ON and OFF STN DBS in the PD-DBS cohort, and on and off dopaminergic medication in a second PD cohort of thirty-two individuals (PD-med). A subset of eleven individuals in the PD-DBS cohort completed the SIP task again off all therapy after three years of continuous DBS to assess progression of gait impairment. Swing time variability was significantly greater (i.e., worse) in PD compared to controls and greater swing time variability was related to greater atrophy of the NBM, as was gait speed. STN DBS significantly improved cardinal motor signs and gait speed but did not improve swing time variability, which was replicated in the second cohort using dopaminergic medication. Swing time variability continued to worsen in PD, off therapy, after three years of continuous STN DBS, and NBM atrophy showed a trend for predicting the degree of increase. In contrast, cardinal motor signs did not progress. These results demonstrate that swing time variability is a reliable marker of cortical cholinergic health, and support a framework in which higher-order aspects of gait control in PD are reliant on the cortical cholinergic system, in contrast to other motor aspects of PD that rely on the dopaminergic network.
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胆碱能和尾状核多巴胺能缺陷的频率在帕金森氏病的预测认知范围内以及相互作用效应的证据。
影响因子：
29
作者：
Bohnen NI;Albin RL;Müller ML;Petrou M;Kotagal V;Koeppe RA;Scott PJ;Frey KA
通讯作者：
Frey KA
影响因子：
4.8
作者：
Bronte-Stewart, Helen;Louie, Stephanie;Henderson, Jaimie M.
通讯作者：
Henderson, Jaimie M.
影响因子：
5.3
作者：
Gratton, Caterina;Yousef, Sahar;Silver, Michael A.
通讯作者：
Silver, Michael A.
影响因子：
48
作者：
Henderson, Emily J.;Lord, Stephen R.;Ben-Shlomo, Y.
通讯作者：
Ben-Shlomo, Y.
影响因子：
9.9
作者：
Bohnen, Nicolaas I.;Frey, Kirk A.;Mueller, Martijn L. T. M.
通讯作者：
Mueller, Martijn L. T. M.