Balance and Gait Disorders Associated with Genetic Inheritance in PD

项目3（霍拉克）：摘要 与PD遗传相关的平衡/步态障碍 认知缺陷和平衡/步态（B&G）障碍都是进行性的，但在人群中是异质性的 帕金森病（PD），可能部分是由于遗传因素。首届PANUC奖 研究表明，APOE ε4或GBA变异增加了不同类型认知障碍的风险， 警局项目3将检验以下假设，即B&G异常的模式，部分是各种 不同类型的认知功能障碍，在APOE ε4、GBA变异或两者都不存在的PD受试者中不同。B&G将成为 在所有临床核心参与者中使用佩戴在脚、腰带和手腕上的新型惯性传感器进行表征。一 快速仪器站立和行走协议，包括安静站立30秒，然后是步骤- 启动、2分钟步行和几个180度转弯量化了行动能力障碍的各个领域， 如姿势摆动面积、步态步速和步态节律。B&G方案也将在同时进行期间重复。 定量认知任务的表现，以确定分散注意力对B&G的影响。我们将测试 我们的假设有三个具体目标：1）横断面：确定PD患者B&G功能障碍的模式， APOE ε4、GBA变体或两者都不存在，并将B&G与这些遗传定义的认知障碍联系起来。 PD的亚类; 2）生理学：将用SAI测量的中枢胆碱能张力与B&G的损害相关联 和注意力在遗传定义的PD子集;和3）纵向：确定纵向下降， 遗传学定义的PD亚群中的B&G、注意力和胆碱能张力这项工作意义重大，因为它 将扩大我们对严重程度和活动性下降的遗传风险的了解，因为它们与认知功能有关。 帕金森病的损害，并奠定了潜在的胆碱能机制与B&G连接的基础 功能障碍该项目的见解，整合在PANUC中，将为认知功能提供新的生物标志物。 和活动能力下降，以改善PD患者的预后和干预措施。

PROJECT 3 (HORAK): ABSTRACT Balance/gait disorders associated with genetic inheritance in PD Cognitive deficits and balance/gait (B&G) disorders are both progressive but heterogeneous among people with Parkinson's disease (PD), and may be due in part to genetic factors. The inaugural PANUC award demonstrated that APOE ε4 or GBA variants increases the risk for different types of cognitive impairment in PD. Project 3 will test the hypothesis that the pattern of B&G abnormalities, in part an expression of various types of cognitive impairment, differ in PD subjects with APOE ε4, GBA variants, or neither. B&G will be characterized in all Clinical Core participants using novel, inertial-sensors worn on the feet, belt, and wrist. A quick Instrumented Stand and Walk protocol that involves standing quietly for 30 seconds, followed by step- initiation, a 2-minute walk, and several 180 degree turns quantifies various domains of mobility disability, such as postural sway area, gait pace, and gait rhythm. The B&G protocol will also be repeated during simultaneous performance of a quantitative cognitive task to determine the effects of divided attention on B&G. We will test our hypotheses with three specific aims: 1) Cross-sectional: Determine patterns of B&G dysfunction in PD with APOE ε4, GBA variants, or neither, and relate B&G to cognitive impairments in these genetically-defined subsets of PD; 2) Physiological: Relate central cholinergic tone, measured with SAI, to impairments of B&G and attention in in genetically-defined subsets of PD; and 3) Longitudinal: Determine the longitudinal decline of B&G, attention, and cholinergic tone in genetically-defined subsets of PD. This work is significant because it will expand our knowledge of genetic risk for severity and decline in mobility as they relate to cognitive impairments in PD, and lay the foundation for potential cholinergic mechanisms linking cognitive with B&G dysfunction. Insights from this project, integrated within the PANUC, will provide new biomarkers for cognitive and mobility decline for better prognosis and interventions for patients with PD.