Exercise Intervention for Slowing HD Progression

运动干预可减缓 HD 进展

• 批准号: 9149031
• 负责人: VINCENT A MAGNOTTA
• 金额: $ 19.06万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-30 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9149031
• 关键词: Accounting; Adenine; Aerobic; Affect; Age; Age of Onset; Area; Atrophic; Basal Ganglia; Blood Vessels; Body Weight decreased; Brain; Brain imaging; Brain-Derived Neurotrophic Factor; Cerebrum; Cognitive; Corpus striatum structure; Creatine; Cytosine; Data; Diagnosis; Diffusion; Diffusion Magnetic Resonance Imaging; Disease Progression; Dose; Eating; Energy Supply; Enzymes; Equilibrium; Event; Exercise; Genes; Glucose; Goals; Growth; Guanine; Health; Home environment; Huntington Disease; Huntington gene; Image; Individual; Intervention; Intervention Studies; Iowa; Lead; Learning; Length; Literature; Magnetic Resonance Imaging; Measures; Metabolic; Metabolic Marker; Metabolism; Moderate Exercise; Motor; Neurodegenerative Disorders; Neurons; Nutrient; Onset of illness; Performance; Physical Exercise; Physical activity; Positioning Attribute; Production; Randomized Controlled Trials; Relaxation; Rest; Strenuous Exercise; Symptoms; Testing; Therapeutic Effect; Time; Triad Acrylic Resin; Universities; VO2max; Walking; Work; base; brain health; exercise intensity; exercise intervention; exercise program; fitness; glucose metabolism; improved; in vivo; insight; lifestyle factors; mitochondrial dysfunction; motor impairment; motor symptom; public health relevance; putamen; randomized trial; symptom treatment; treatment response; vigorous intensity; white matter

 DESCRIPTION (provided by applicant): Recent work suggests that exercise that moderate-to-vigorous intensity physical exercise is associated with slowing of symptom progression (motor, cognitive, and psychiatric) in prodromal Huntington's Disease (HD). In addition, the literature shows that the intervention is well tolerated in prodromal HD. In subjects without HD, moderate intensity physical exercise has been shown to improve white matter integrity, increase caudate neuronal activity, and increase striatum activation in spatial learning. Exercise has been shown to increase metabolic enzymes, promote growth of blood vessels to provide increased nutrient and energy supply, increase central BDNF expression, and to promote local glucose metabolism in the basal ganglia. We hypothesize that initiating a moderate intensity physical exercise program will substantially slow progressive striatal volume loss and improve connectivity in prodromal HD. To test this hypothesis, we will undertake a six- month randomized controlled study of home-based moderate intensity aerobic walking exercise program or balance and toning control. In the proposed study, MR will be used to assess the impact of fitness and an exercise intervention on well established markers for HD progression in the brain including: volume of the caudate and putamen and white matter integrity using diffusion weighted imaging. In addition, we will employ a quantitative relaxation parameter, T1 relaxation in the rotating frame (T1ρ), which we have shown to be sensitive to prodromal HD progression. To evaluate the influence of fitness and therapeutic effect of moderate intensity exercise in prodromal HD, we propose two specific aims: 1) Does baseline fitness account for variance in motor function and brain imaging measures in prodromal HD? and 2) Does a moderate-to-vigorous exercise intervention influence the progression of motor impairment and brain degeneration in prodromal HD? This study will provide insight into the cascade of events that lead to anatomical changes in prodromal HD and will help reveal how exercise improves motor, cognitive, and psychiatric health in subjects with the Htt gene expansion.

 描述（由申请人提供）：最近的研究表明，中等至剧烈强度的体育锻炼与前驱期亨廷顿病（HD）的症状进展（运动、认知和精神）减缓相关。此外，文献显示，前驱HD患者对干预的耐受性良好。在没有HD的受试者中，中等强度的体育锻炼已被证明可以改善白色物质的完整性，增加尾状核神经元的活动，并增加空间学习中的纹状体激活。运动已被证明增加代谢酶，促进血管生长以提供增加的营养和能量供应，增加中枢BDNF表达，并促进基底神经节中的局部葡萄糖代谢。我们假设，开始一个中等强度的体育锻炼计划将大大减缓进行性纹状体体积损失和改善连接前驱HD。为了验证这一假设，我们将进行一项为期六个月的随机对照研究，以家庭为基础的中等强度有氧步行锻炼计划或平衡和调整控制。在拟定的研究中，MR将用于评估健身和运动干预对脑内HD进展的既定标志物的影响，包括：使用弥散加权成像的尾状核和壳核体积以及白色物质完整性。此外，我们将采用一个定量弛豫参数，旋转坐标系中的T1弛豫（T1ρ），我们已经证明它对前驱HD进展敏感。为了评估适能和中等强度运动对前驱期HD的治疗效果的影响，我们提出了两个具体目标：1）基线适能是否能解释前驱期HD运动功能和脑成像测量的差异？中度至剧烈运动干预是否会影响前驱HD患者运动障碍和脑变性的进展？这项研究将深入了解导致前驱HD解剖学变化的事件级联，并将有助于揭示运动如何改善Htt基因扩增受试者的运动，认知和精神健康。