Vestibulopathy, imbalance and gait disturbances in Parkinson disease

帕金森病的前庭病、失衡和步态障碍

• 批准号: 10396478
• 负责人: Nicolaas Ida Bohnen
• 金额: --
• 依托单位: VETERANS HEALTH ADMINISTRATION
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10396478
• 关键词: Accounting; Activities of Daily Living; Acute; Address; Affect; Age; Area; Behavior; Bilateral; Brain; Brain Pathology; Chronic; Clinical; Clinical assessments; Communities; Cross-Sectional Studies; Data; Denervation; Disease; Dopamine; Elderly; Eligibility Determination; Emerging Technologies; Equilibrium; Etiology; Feasibility Studies; Freezing; Frequencies; Functional disorder; Gait; Gait abnormality; Goals; Home; Impairment; Intervention; Knowledge; Link; Long-Term Effects; Methods; Motor; Movement; Nature; Neurodegenerative Disorders; Parkinson Disease; Participant; Pathologic; Persons; Pharmaceutical Preparations; Phase II Clinical Trials; Physical activity; Play; Population; Positron-Emission Tomography; Prevalence; Quality of life; Refractory; Rehabilitation therapy; Research; Resistance; Rest Tremor; Risk Factors; Role; Severities; Societies; System; Testing; Veterans; age related neurodegeneration; caloric stimulation; clinical application; clinical practice; deconditioning; dopamine transporter; fall risk; falls; fear of falling; feasibility trial; improved; motor function improvement; neglect; nerve supply; novel; portability; posture instability; programs; sedentary; translational impact; treatment responders; treatment response

The management of dopamine resistant postural instability and gait difficulty (PIGD) features, such as freezing of gait (FoG), represents perhaps the most important unmet clinical need in Parkinson's disease (PD). Research into the role of the vestibular system in the etiology of FoG has largely been neglected. Age- associated vestibular impairment (presbyvestibulopathy, PVP) is present in about half of older community- dwelling older persons and is a significant contributor to imbalance and falls. PVP is also common in PD, an age-related neurodegenerative disorder. We have novel preliminary data showing that PVP may be an important factor contributing to FoG. Confirmation of a mechanistic link between vestibular dysfunction and FoG has high clinical translational impact and may augur novel vestibular rehabilitation interventions, such as in-home portable thermoneuromodulation (TNM) to treat PD Veterans with otherwise treatment-refractory FoG. Plan: Our main aim will be a cross-sectional study in 64 Veterans with PD to investigate the relationship between PVP and FoG. Our exploratory aim will be a mechanistic feasibility trial of portable TNM in PD Veterans with FoG and PVP. Methods: We will perform detailed clinical, including dedicated motor and vestibular testing. PE2I dopamine transporter (DAT) PET will be used to assess the integrity of dopaminergic nigrostriatal innervation. Hypothesis 1: The prevalence of FoG is higher in Veterans with PD who also have evidence of PVP compared to those without PVP independent of nigrostriatal dopaminergic losses. Exploratory hypothesis: Active TNM stimulation will result in improved FoG severity ratings compared to sham stimulation in PD Veterans with FoG and PVP.

耐多巴胺的姿势不稳定性和步态难度（PIGD）的管理，例如冷冻 步态（雾）的含量可能代表了帕金森氏病（PD）中最重要的未满足临床需求。 对前庭系统在雾的病因中的作用的研究在很大程度上被忽略了。年龄- 相关的前庭障碍（Persbyvestibulopathy，PVP）大约有一半的较老的社区 - 居住的老年人，是失衡和跌倒的重要贡献者。 PVP在PD中也很常见 与年龄有关的神经退行性疾病。我们有新的初步数据，表明PVP可能是 造成雾的重要因素。确认前庭功能障碍与 雾具有较高的临床翻译影响，可能会增强新型的前庭康复干预措施，例如 内部便携式热素调节（TNM），以治疗难治性雾对PD退伍军人进行治疗。 计划：我们的主要目的是在64名有PD退伍军人的退伍军人中进行横断面研究 在PVP和雾之间。我们的探索目标将是PD中便携式TNM的机械可行性试验 带有雾和PVP的退伍军人。 方法：我们将执行详细的临床，包括专用运动和前庭测试。 PE2I多巴胺 转运蛋白（DAT）PET将用于评估多巴胺能神经支配的完整性。 假设1：PD的退伍军人中雾的患病率较高，他们也有PVP证据 与没有PVP的人相比，独立于黑质纹状体多巴胺能损失。 探索性假设：主动TNM刺激将导致与 PD退伍军人的假刺激，具有雾和PVP。