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定和步态困难（PIGD）特征的管理，如冻结 步态（FoG），可能代表帕金森病（PD）中最重要的未满足的临床需求。 前庭系统在FOG病因学中的作用研究在很大程度上被忽视了。年龄- 相关的前庭损害（老年性前庭病变，PVP）存在于大约一半的老年人中， 是造成不平衡和福尔斯的重要因素。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的初步数据显示PVP可能是一种 这是导致FoG的重要因素。确认前庭功能障碍与 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，如 家庭便携式热神经调节（TNM）治疗PD退伍军人，否则治疗难治性FoG。 计划：我们的主要目的是在64名患有PD的退伍军人中进行横断面研究，以调查 PVP和FoG的区别我们的探索性目标将是便携式TNM在PD中的机械可行性试验 拥有FoG和PVP的老兵。 方法：我们将进行详细的临床，包括专门的运动和前庭测试。PE 2 I多巴胺 将使用多巴胺转运体（DAT）PET来评估多巴胺能黑质纹状体神经支配的完整性。 假设1：有PVP证据的PD退伍军人的FoG患病率较高 与没有PVP的人相比，与黑质纹状体多巴胺能损失无关。 探索性假设：主动TNM刺激将导致FoG严重程度评级改善， PD退伍军人FoG和PVP的假刺激。