Genetic influences on response to gait rehabilitation in Parkinson’s disease

遗传因素对帕金森病步态康复反应的影响

• 批准号: 10174833
• 负责人: CYRUS P ZABETIAN
• 金额: --
• 依托单位: VA PUGET SOUND HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10174833
• 关键词: Affect; Aging; Alleles; Alzheimer' s Disease; Area; Attention; Birth; Brain; Brain-Derived Neurotrophic Factor; Caregiver Burden; Clinical; Cognition; Cognitive; Complex; Cues; Data; Diagnosis; Disease; Enrollment; Exposure to; Foundations; Gait; Gait speed; Genes; Genetic; Genetic Variation; Genetic study; Genomics; Genotype; Goals; Health; Health system; Herbicides; Human Genome Project; Impaired cognition; Impairment; Individual; Intervention; Knowledge; Learning; Measures; Medicine; Memory; Military Personnel; Morbidity - disease rate; Motor; Nerve Degeneration; Neurodegenerative Disorders; Operative Surgical Procedures; Outcome; Parkinson Disease; Patients; Performance; Pharmacology; Physical Endurance; Physical Exercise; Physical Rehabilitation; Physical therapy; Play; Population; Process; Quality of life; Rehabilitation Outcome; Rehabilitation therapy; Research; Role; Services; Speed; Subgroup; Testing; Time; Training; Training Programs; Translating; Traumatic Brain Injury; United States; Variant; Veterans; Walking; Work; agent orange; apolipoprotein E-4; base; clinical care; cognitive benefits; cognitive change; cognitive function; cognitive performance; cognitive testing; common symptom; design; disability; dosage; effective therapy; executive function; experience; fall risk; follow-up; gait examination; gait rehabilitation; genetic profiling; genetic variant; health care quality; improved; individual variation; mortality; motor learning; patient population; patient response; patient subsets; precision medicine; processing speed; programs; rehabilitation strategy; relating to nervous system; repaired; response; treadmill; treadmill training; treatment response; virtual; walking speed

The completion of the Human Genome Project in 2003 marked the beginning of the genomic era and the birth of “personalized” (precision) medicine. In the last decade, genetics have provided a new understanding of predicting, diagnosing, and treating individual health conditions. Indeed, such precision medicine has begun to impact virtually all areas of medicine, with significant potential to influence the timing, dosage, and intensity of physical rehabilitation. The long-term goals of this research are: (1) to determine if certain genetic variants associated to learning impairments impact the motor and cognitive benefit experienced in response to physical rehabilitation in Veterans with Parkinson's disease (PD), and (2) to use that knowledge to identify subpopulations of patients that may require rehabilitative strategies tailored to their genotype to optimize physical rehabilitation. To achieve these goals we will enroll 30 Veterans with PD in a 10-week moderate intensity gait training program consisting of 2 times per week treadmill training with verbal cues for gait quality. Aim 1 will examine the association between variants in 2 genes known to affect cognition and motor learning (APOE-ɛ4 and BDNF-Met66), and motor improvements after gait training. Specifically, changes in walking from during and after training will be sensitively and objectively assessed using state-of-the-art quantitative gait analysis, and compared between three genotype groups (carriers of BDNF-Met66 (N=10), carriers of APOE-ɛ4 (N=10) and those not carrying either of those variants (N=10)). Aim 2 will examine the effect of APOE-ɛ4 and BDNF-Met66 genetic variants on cognitive changes in response to this training program. In order to do this we will measure cognitive performance pre- and post-training using a brief, targeted battery aimed at assessing attention, processing speed, executive function, and learning/memory, the domains more affected, and more likely to improve with physical exercise in PD. We will test the hypothesis that Veterans with PD who carry an APOE-ɛ4 or BDNF-Met66 allele will demonstrate smaller improvements in gait (Aim 1) and cognition (Aim 2) in response to a 10-week gait training program. Overall the results of this project will enhance our knowledge regarding the influence of different genetic profiles in the response to physical rehabilitation in Veterans with PD, and will generate supporting data that will translate to more personalized and effective rehabilitation programs for people with PD.

2003年人类基因组计划的完成标志着基因组时代的开始 “个性化”（精准）医学的诞生在过去十年中，遗传学提供了一种新的方法。 事实上，对预测、诊断和治疗个人健康状况的理解。 精准医疗已开始影响几乎所有医学领域，具有巨大的潜力 影响身体康复的时间、剂量和强度。 这项研究的长期目标是：（1）确定某些遗传变异是否与 学习障碍会影响身体反应中的运动和认知益处 患有帕金森病 (PD) 的退伍军人的康复，以及 (2) 利用这些知识来识别 可能需要根据其基因型制定康复策略的患者亚群 为了实现这些目标，我们将在 10 周内招募 30 名患有 PD 的退伍军人。 中等强度步态训练计划，包括每周 2 次跑步机训练和言语训练 目标 1 将检查已知影响步态的 2 个基因变异之间的关联。 认知和运动学习（APOE-ɛ4 和 BDNF-Met66），以及步态训练后的运动改善。 具体来说，训练期间和训练后步行的变化将被敏感且客观地记录下来。 使用最先进的定量步态分析进行评估，并在三种基因型之间进行比较 群体（BDNF-Met66 携带者 (N=10)、APOE-ɛ4 携带者 (N=10) 以及不携带其中任何一种的群体） 目标 2 将检查 APOE-ɛ4 和 BDNF-Met66 遗传变异对这些变异的影响。 为了做到这一点，我们将测量认知能力以响应该培训计划。 使用简短的、有针对性的电池来评估训练前和训练后的表现，旨在评估注意力， 处理速度、执行功能和学习/记忆、受影响较大的领域等等 患有帕金森病的退伍军人可能会通过体育锻炼而得到改善。 携带 APOE-ɛ4 或 BDNF-Met66 等位基因将在步态方面表现出较小的改善（目标 1）并且 总体而言，该项目的结果将是针对为期 10 周的步态训练计划的认知（目标 2）。 增强我们对不同基因谱对身体反应影响的了解 患有 PD 的退伍军人康复，并将生成支持数据，这些数据将转化为更多 为帕金森病患者提供个性化且有效的康复计划。

项目成果

Associations between baseline cognitive status and motor outcomes after treadmill training in people with Parkinson's disease: a pilot study.

帕金森病患者跑步机训练后基线认知状态与运动结果之间的关联：一项试点研究。

• DOI: 10.1080/09638288.2023.2189318
• 发表时间: 2024
• 期刊: Disability and rehabilitation
• 影响因子: 2.2
• 作者: Amin,RaimaM;Phillips,JamesJ;Humbert,AndrewT;Cholerton,BrennaA;Short,ValerieD;Smith,MelissaJ;Zabetian,CyrusP;Mata,IgnacioF;Kelly,ValerieE
• 通讯作者: Kelly,ValerieE