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.

多巴胺抵抗姿势不稳定和步态困难(PIGD)特征的处理，如冻结 步态(雾)，可能是帕金森病(PD)最重要的未得到满足的临床需求。 前庭系统在雾的病因中的作用的研究在很大程度上被忽视了。年龄- 相关的前庭功能障碍(老年性前庭病变，PVP)出现在大约一半的老年社区- 老年人居住，是造成不平衡和跌倒的重要因素。PVP在帕金森氏病中也很常见， 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 造成大雾的重要因素。确认前庭功能障碍和前庭功能障碍之间的机制联系 雾具有很高的临床翻译影响，并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)治疗患有难治性雾的帕金森病退伍军人。 计划：我们的主要目标是对退伍军人与帕金森病的关系进行横断面研究 在PVP和雾之间。我们的探索性目标将是一项便携式TNM在PD中的机械可行性试验 有雾和PVP的退伍军人。 方法：我们将进行详细的临床检查，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黑质纹状体神经支配的完整性。 假设1：患有PD的退伍军人中雾的患病率更高，他们也有PVP的证据 与没有PVP的患者相比，黑质纹状体多巴胺能损失独立。 探索性假设：积极的TNM刺激将导致雾严重程度评级比 假刺激对伴有雾和PVP的PD退伍军人的影响