Alzheimer's Supplement to Hemodialysis-based interventions to preserve cognitive function

阿尔茨海默病补充血液透析干预措施以保持认知功能

• 批准号: 10286431
• 负责人: Mara A. McAdams DeMarco
• 金额: $ 39.86万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-01-09 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10286431
• 关键词: Adult; Alzheimer' s Disease; Alzheimer' s disease related dementia; Cessation of life; Characteristics; Clinical; Cognition; Communities; Consensus; Country; Data; Dementia; Diagnosis; Diagnostic; Dialysis procedure; Elderly; End stage renal failure; Enrollment; Ethnic Origin; Frequencies; General Population; Hemodialysis; Hospitalization; Hour; Impairment; Intention; Intervention; Kidney Diseases; Learning; Life; Measures; Modality; Modification; Nephrology; Outcome; Participant; Patients; Pharmaceutical Preparations; Pilot Projects; Provider; Public Health; Race; Randomized; Randomized Controlled Trials; Records; Renal dialysis; Reporting; Research; Rest; Sleep; Subgroup; Testing; Time; Trail Making Test; Transplantation; Woman; base; cognitive function; cognitive training; disability; effective intervention; executive function; exercise training; experience; feasibility testing; follow-up; high risk; improved; insight; interest; lifetime risk; men; neurocognitive test; novel; preservation; prevent; primary outcome; public health relevance; secondary outcome; sex; standard of care; symposium; tv watching

ABSTRACT: RELEVANCE TO ADRD 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, death and dementia. In fact, our preliminary data suggest that HD patients have a 21-25% lifetime risk of receiving a dementia diagnosis and 4-5% lifetime risk of receiving an Alzheimer's disease and related dementias (ADRD) diagnosis; they are 19-times and 7-times more likely to be diagnosed with dementia and ADRD, respectively than older adults without ESRD. Yet, only half of patients who would meet diagnostic criteria for dementia receive a diagnosis. Among HD patients, dementia and ADRD are major public health challenges. Studies of older adults suggest that the only effective interventions for preserving executive function and preventing ADRD are cognitive training (CT) and/or exercise training (ET). However, these modalities have not been tested in HD patients; even younger HD patients suffer substantial executive function impairment leading to dementia/ADRD and could benefit from the 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 and subsequent ADRD. 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. In just 3 months, CT and ET preserved executive function compared to a striking decline with standard of care. We have built upon this pilot study and are testing interventions on a wider breadth of HD patients, for longer durations, and alone versus in combination. Our ongoing RCT (98/200 participants enrolled) tests the impact of intradialytic CT, ET, and combined CT and ET on the executive function decline associated with HD. To this study we wish to add the novel endpoint of dementia/ADRD and ascertained through novel follow-up. We propose the following aims: To 1) add a novel secondary outcomes of dementia and ADRD to an existing RCT of intradialytic cognitive training (CT) and/or exercise training (ET); 2) To quantify the effects of intradialytic cognitive training (CT) and/or exercise training (ET) on dementia and ADRD among high-risk subgroups. Through this RCT, we will learn the impact of two potential non-pharmacological interventions, cognitive and exercise training, in preserving executive function during HD and the long-term outcome of dementia and ADRD.

摘要：与ADRD的相关性 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 损伤率比一般人群高3倍，导致住院、残疾、死亡和 痴呆症。事实上，我们的初步数据表明，HD患者一生中有21-25%的风险接受 痴呆症诊断和4-5%患阿尔茨海默病和相关痴呆(ADRD)的终生风险 诊断；他们被诊断为痴呆症和ADRD的可能性分别高出19倍和7倍 比没有ESRD的老年人要好。然而，只有一半符合痴呆症诊断标准的患者 接受诊断。在HD患者中，痴呆症和ADRD是主要的公共卫生挑战。的研究 老年人认为，保护执行功能和预防的唯一有效干预措施 ADRD是认知训练(CT)和/或运动训练(ET)。然而，这些模式并没有 在HD患者中进行测试；即使是年轻的HD患者也会遭受严重的执行功能障碍，导致 痴呆症/ADRD，并可从干预中受益。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 功能下降和随后的ADRD。为了测试传统透析干预的可行性，我们进行了一项 对20名HD患者进行RCT试点，将护理标准与CT或ET进行比较；即使在这项试点中，我们也发现 传统的CT和ET保留了执行功能。正如预期的那样，接受治疗的患者的执行功能 护理标准大幅下降3个月(差异=47.4秒，P=0.006)；然而，这种下降 在接受CT或ET的患者中未发现。在短短3个月内，CT和ET保留了执行功能 相比之下，护理标准显著下降。我们在这项初步研究的基础上进行了测试 对更广泛的HD患者进行干预，持续时间更长，单独或联合干预。我们的 正在进行的随机对照试验(98/200名参与者参加)测试传统透析中CT、ET以及联合CT和ET的影响 与HD相关的执行功能下降。在这项研究中，我们希望增加一个新的终点 痴呆症/ADRD，并通过新的随访确定。我们提出以下目标：1)增加一部小说 痴呆和ADRD与现有的透析内认知训练(CT)和/或随机对照试验的继发性结局 运动训练(ET)；2)量化传统认知训练(CT)和/或运动训练的效果 (ET)关于高危亚群中的痴呆症和ADRD。通过这次RCT，我们将了解到两个 潜在的非药物干预，认知和运动训练，以保持执行功能 HD期间及痴呆症和ADRD的长期结局。