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: 10179754
• 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/10179754
• 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; 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.

多巴胺抵抗性姿势不稳和步态困难 (PIGD) 特征的管理，例如冻结 步态（FoG）的监测可能代表了帕金森病（PD）中最重要的未满足的临床需求。 前庭系统在 FoG 病因学中的作用的研究在很大程度上被忽视了。年龄- 大约一半的老年社区存在相关的前庭功能障碍（老年前庭病，PVP） 居住的老年人是造成不平衡和跌倒的重要因素。 PVP 在 PD 中也很常见， 与年龄相关的神经退行性疾病。我们有新颖的初步数据表明 PVP 可能是一种 影响 FoG 的重要因素。证实前庭功能障碍与 FoG 具有很高的临床转化影响，可能预示着新的前庭康复干预措施，例如 家用便携式热神经调节 (TNM)，用于治疗 PD 退伍军人的其他难治性 FoG。 计划：我们的主要目标是对 64 名患有 PD 的退伍军人进行横断面研究，以调查两者之间的关系 介于PVP和FoG之间。我们的探索目标是便携式 TNM 在 PD 中的机械可行性试验 拥有 FoG 和 PVP 的退伍军人。 方法：我们将进行详细的临床，包括专门的运动和前庭测试。 PE2I多巴胺 转运蛋白 (DAT) PET 将用于评估多巴胺能黑质纹状体神经支配的完整性。 假设 1：患有 PD 并有 PVP 证据的退伍军人中 FoG 的患病率较高 与没有 PVP 的患者相比，与黑质纹状体多巴胺能损失无关。 探索性假设：与相比，主动 TNM 刺激将导致 FoG 严重程度评级改善 使用 FoG 和 PVP 对 PD 退伍军人进行假刺激。