Hemodialysis-based interventions to preserve cognitive function

摘要 超过64万美国成年人患有终末期肾病，其中95%的人在余生或 直到移植。肾脏疾病和HD对认知功能有显著影响，尤其是高阶 执行职能。只有13%的HD患者认知正常；HD患者有执行功能 损伤率是一般人群的3倍，导致住院、残疾和死亡。 对老年人的研究表明，保护执行功能的唯一有效干预措施是 认知训练(CT)和/或运动训练(ET)。这些模式尚未针对管理人员进行测试 HD患者的功能保留；甚至年轻的HD患者也有实质性的执行功能 损害，并可从这些干预措施中受益。HD频率(每周3次)和持续时间(4-6次 小时/疗程)使HD患者成为传统透析中CT和/或ET的“俘虏观众”，以减轻执行力 功能衰退。在初步研究中，HD患者报告说他们大部分时间都在看电视； 传统的CT和/或ET可以替代这些被动活动。在初步研究中，87%的肾病 提供者认为他们的患者会对传统分析CT感兴趣，83%的人认为他们的 患者会对传统的ET感兴趣。在HD患者中，67%的人希望改善他们的认知 通过CT和71%的人希望在进行HD的同时通过ET提高他们的力量和认知能力。 为了测试透析内干预的可行性，我们对20名HD患者进行了试验性RCT，比较 对CT或ET的标准护理；即使在这位飞行员中，我们发现传统透析中的CT和ET保留了执行 功能。正如预期的那样，接受标准护理的患者的执行功能大幅下降了3% 月(差值=47.4秒，P=0.006)；然而，在接受CT或 Et.与护理标准相比，平均变化为-46.72秒(95%可信区间：-91.12，- CT为2.31(P=0.04)，ET为-56.21秒(95%CI：-105.86，-6.56；P=0.03)。在短短3个月内，CT和ET 与护理标准的显著下降相比，执行功能得到了保留。 为了正确测试透析中CT和/或ET对HD相关执行功能下降的影响， 我们提出以下目标：1)进行一项随机对照试验，以评估执行功能衰退的背景下 2)量化分析CT和/或ET对ESRD特异性临床的影响 结果，3)量化传统分析中CT和/或ET对以患者为中心的结果的影响。 通过这项随机对照试验，我们将了解两种潜在的非药物干预措施的影响，认知干预和 运动训练，在HD期间保持执行功能。如果成功，这将改善HD的结果 &gt；64万名患有终末期肾病的成年人。第一次，我们将有经过验证的有益活动取代典型的 血液透析患者的被动活动。我们的发现将在全国各地的透析中心实施 帮助减少执行功能的下降。

ABSTRACT Over 640,000 US adults suffer from ESRD, >95% of whom receive hemodialysis (HD) for the rest of their life or until transplantation. Kidney disease and HD significantly impact cognitive function, especially higher-order executive function. Only 13% of HD patients have normal cognition; HD patients experience executive function impairment at a rate 3-fold higher than the general population, leading to hospitalization, disability, and death. Studies of older adults suggest that the only effective interventions for preserving executive function are cognitive training (CT) and/or exercise training (ET). These modalities have not been tested for executive function preservation in HD patients; even younger HD patients suffer substantial executive function impairment and could benefit from these interventions. HD frequency (3 sessions a week) and duration (4-6 hours/session) makes HD patients a “captive audience” for intradialytic CT and/or ET to mitigate executive function decline. In preliminary studies, HD patients reported spending most of their time watching TV; intradialytic CT and/or ET could replace these passive activities. In preliminary studies, 87% of nephrology providers believed that their patients would be interested in intradialytic CT and 83% believed that their patients would be interested in intradialytic ET. Among HD patients, 67% wanted to improve their cognition through CT and 71% wanted to improve their strength and cognition through ET while undergoing HD. To test the feasibility of intradialytic interventions, we conducted a pilot RCT of 20 HD patients, comparing standard of care to CT or ET; even in this pilot, we found that intradialytic CT and ET preserved executive function. As expected, executive function in patients receiving standard of care declined substantially by 3 months (difference=47.4 seconds, P=0.006); however, this decline was not seen among those receiving CT or ET. Compared with standard of care, the difference in mean change was -46.72 seconds (95% CI: -91.12, - 2.31; P=0.04) for CT and -56.21 seconds (95% CI: -105.86, -6.56; P=0.03) for ET. In just 3 months, CT and ET preserved executive function compared to a striking decline with standard of care. To properly test the impact of intradialytic CT and/or ET, on the executive function decline associated with HD, we propose the following aims: 1) To conduct an RCT to evaluate executive function decline in the setting of intradialytic CT and/or ET, 2) To quantify the effects of intradialytic CT and/or ET on ESRD-specific clinical outcomes, 3) To quantify the effects of intradialytic CT and/or ET, on patient-centered outcomes. Through this RCT, we will learn the impact of two potential non-pharmacological interventions, cognitive and exercise training, in preserving executive function during HD. If successful, this will improve HD outcomes of >640,000 adults with ESRD. For the first time, we will have validated, beneficial activities replace the typical passive activities of HD patients. Our findings will be implementable in dialysis centers across the country to help reduce the decline in executive function.