Health, Psychology and Communities Research Centre, Department of Psychology, Manchester Metropolitan University, Manchester, United Kingdom.
School of Sport, Exercise and Rehabilitation Sciences, and Centre for Human Brain Health, the University of Birmingham, Birmingham, United Kingdom.
Mov Disord. 2020 Jul;35(7):1199-1207. doi: 10.1002/mds.28051. Epub 2020 May 13.
There is an urgent need to identify individuals at risk of postural instability and gait difficulties, and the resulting propensity for falls, in Parkinson's disease.
Given known relationships between posture and gait and degeneration of the cholinergic pedunculopontine nucleus, we investigated whether metrics of pedunculopontine nucleus microstructural integrity hold independent utility for predicting future postural instability and gait difficulties and whether they could be combined with other candidate biomarkers to improve prognostication of these symptoms.
We used stereotactic mapping of the pedunculopontine nucleus and diffusion tensor imaging to extract baseline pedunculopontine nucleus diffusivity metrics in 147 participants with Parkinson's disease and 65 controls enrolled in the Parkinson's Progression Markers Initiative. We also recorded known candidate markers of posture and gait changes: loss of caudate dopamine and CSF β-amyloid 1-42 levels at baseline; as well as longitudinal progression motor symptoms over 72-months.
Survival analyses revealed that reduced dopamine in the caudate and increased axial diffusivity in the pedunculopontine nucleus incurred independent risk of postural instability and gait difficulties. Binary logistic regression and receiver operating characteristics analysis in 117 participants with complete follow-up data at 60 months revealed that only pedunculopontine nucleus microstructure provided more accurate discriminative ability for predicting future postural instability and gait difficulties than clinical and demographic variables alone.
Dopaminergic and cholinergic loss incur independent risk for future postural instability and gait difficulties, and pedunculopontine nucleus microstructure can be used to prognosticate these symptoms from early Parkinson's disease stages. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
迫切需要识别帕金森病患者中存在姿势不稳定和步态困难风险，以及由此导致跌倒倾向的个体。
鉴于姿势和步态与胆碱能脑桥被盖核退化之间的已知关系，我们研究了脑桥被盖核微观结构完整性的指标是否对预测未来的姿势不稳定和步态困难具有独立的效用，以及它们是否可以与其他候选生物标志物结合使用以改善对这些症状的预后。
我们使用立体定向脑桥被盖核图谱和弥散张量成像，从帕金森病进展标志物倡议中纳入的 147 名帕金森病患者和 65 名对照者中提取基线脑桥被盖核弥散率指标。我们还记录了已知的姿势和步态变化候选标志物：基线时尾状核多巴胺丢失和 CSF β-淀粉样蛋白 1-42 水平；以及 72 个月的纵向进展运动症状。
生存分析表明，尾状核多巴胺减少和脑桥被盖核轴突弥散度增加与姿势不稳定和步态困难具有独立的风险。在 117 名有 60 个月完整随访数据的参与者中进行二元逻辑回归和接受者操作特征分析显示，只有脑桥被盖核微观结构为预测未来的姿势不稳定和步态困难提供了比临床和人口统计学变量更准确的鉴别能力。
多巴胺能和胆碱能丧失与未来的姿势不稳定和步态困难有独立的风险，并且脑桥被盖核微观结构可用于从帕金森病早期阶段预测这些症状。
