Exercise training and cognitive and physical function in CKD

描述（由申请人提供）：慢性肾脏疾病（CKD）在老年人中越来越普遍，并伴有超过进展到肾衰竭的后遗症。这些后遗症包括神经认知和身体功能障碍，即使考虑到潜在心血管疾病和糖尿病等常见合并症的差异，CKD患者出现这两种疾病的比例也明显更高。可能解释这些损伤的因素包括内皮功能障碍和炎症，这两者在CKD中更常见，并且与一般人群的认知和身体功能障碍有关。迄今为止，没有任何医学干预措施被证明可以预防这一高危人群的认知和身体功能障碍。然而，几项针对CKD患者的初步研究已经检查了运动对身体表现、有氧能力和健康相关生活质量（HRQoL）的影响，表明有监督的运动训练计划可能会引起功能改善。此外，对健康成人的研究表明，有氧运动训练可以改善认知功能、身体表现、血管功能、炎症和血管危险因素。我们假设运动训练可以改善老年非透析CKD患者的神经认知功能、身体功能和健康相关的生活质量，这些结果部分是由炎症、血管功能、血脂、血压和胰岛素抵抗的改善所介导的。我们提出了一项双中心随机平行组临床试验，以评估12个月有氧和阻力运动训练与定向健康教育对照对120名老年社区3b-4期CKD患者神经认知功能、身体表现和HRQoL的影响。我们将在基线和6个月和12个月后对以下结果进行详细测量：1)精神运动速度、执行功能和记忆/学习的神经认知测试；2)有氧能力（峰值V02）；3)体能表现包括次最大步行速度、定时起走测试、膝关节伸肌力量、短体能表现电池；4) HRQoL（简写-36）；5)微血管功能激光多普勒血流仪；6)炎症（hs-CRP和IL-6）和血管危险因素（血脂、血压、胰岛素抵抗）。我们将量化运动训练对主要结果的影响，并检查运动相关的炎症、微血管功能和血管危险因素的改善，作为运动对认知和身体表现有益影响的中介。我们已经组建了一个多学科团队，与nia资助的克劳德D.佩珀老年美国人独立中心进行跨机构合作，该中心隶属于马里兰大学和塔夫茨大学，它们共同拥有进行长期锻炼临床试验所需的资源和经验。这项试验的结果对于确定改善这一高危人群的功能状态和最终预防残疾的方法至关重要。

DESCRIPTION (provided by applicant): Chronic kidney disease (CKD) is increasingly prevalent in the elderly and carries sequelae that extend beyond progression to kidney failure. These sequelae include neurocognitive and physical dysfunction, both of which occur at markedly higher rates in CKD patients, even after accounting for differences in common co-morbidities including underlying cardiovascular disease and diabetes. Factors that may explain these impairments include endothelial dysfunction and inflammation, both of which are more frequent in CKD and are associated with cognitive and physical dysfunction in the general population. To date, no medical interventions have been shown to prevent cognitive and physical dysfunction in this exceedingly high-risk population. However, several pilot studies in individuals with CKD have examined the effect of exercise on physical performance, aerobic capacity, and health-related quality of life (HRQoL), suggesting that it may be possible to elicit functional improvements with supervised exercise training programs. Further, studies in healthy adults suggest aerobic exercise training may improve cognitive function, physical performance, vascular function, inflammation, and vascular risk factors. We hypothesize that exercise training will improve neurocognitive function, physical function, and health- related quality of life in older non-dialysis CKD patients, and that these results are mediated in part by improvements in inflammation, vascular function, lipids, blood pressure and insulin resistance. We propose a dual-center randomized parallel-group clinical trial to evaluate the effects of 12 months aerobic and resistance exercise training compared with directed health education control on neurocognitive function, physical performance, and HRQoL in 120 older community-dwelling adults with stage 3b-4 CKD. We will perform detailed measures at baseline and after 6 and 12 months of the following outcomes: 1) Neurocognitive tests of psychomotor speed, executive functions, and memory/learning; 2) Aerobic capacity (peak V02); 3) Physical performance including sub maximal walking speed, timed get up and go test, knee extensor strength, and short physical performance battery; 4) HRQoL (Short Form-36); 5) Microvascular function using laser Doppler flowmetry; 6) Inflammation (hs-CRP and IL-6) and vascular risk factors (lipids, BP, insulin resistance). We will quantify the effects of exercise training on the primary outcomes, and examine exercise-related improvements of inflammation, microvascular function, and vascular risk factors as mediators of the beneficial effects of exercise on cognition and physical performance. We have assembled a multidisciplinary team for a cross-institutional collaboration of the NIA-funded Claude D. Pepper Older Americans Independence Centers affiliated with University of Maryland and Tufts University, which together have the resources and experience necessary to conduct a long-term exercise clinical trial. The results of this trial will be essential in identifying methods to improve functional status and ultimately prevent disability in this high-risk population. PUBLIC HEALTH RELEVANCE: Chronic Kidney Disease (CKD) is exceedingly common in older adults, in whom it is associated with impairment in cognition and physical function. The purpose of this study is to test the effects of 12 months aerobic and resistance exercise training compared to health education on cognitive and physical performance in 120 older adults with chronic kidney disease not requiring dialysis. The results of this study will be essential for demonstrating the effectiveness of exercise in improving function and ultimately preventing disability in this high-risk population of older adults.