Frailty and post-liver transplant delirium and cognitive impairment in older recipients

老年受者的虚弱、肝移植后谵妄和认知障碍

• 批准号: 10621164
• 负责人: Jessica Moore Ruck
• 金额: $ 8.98万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10621164
• 关键词: Acute; Advocate; Affect; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; American; Biology; Biometry; Caring; Characteristics; Chronic; Cohort Studies; Complication; Data Analyses; Delirium; Doctor of Philosophy; Elderly; Enrollment; Epidemiologic Methods; Equation; Funding; Future; General Population; Gerontology; Goals; Health; Hepatic Encephalopathy; Hospital Mortality; Hospitals; Immunosuppression; Impaired cognition; Incidence; Individual; Inflammation; Inflammatory; Intervention; Investigation; Kolmogorov-Smirnov Test; Learning; Length; Liver; Logistic Regressions; Longitudinal cohort study; Measurement; Measures; Mediator; Memory; Mentorship; Methods; Modeling; Neurocognitive; Neurologic Symptoms; Operative Surgical Procedures; Outcome; Outcomes Research; Participant; Patients; Pharmaceutical Preparations; Phenotype; Population; Population Distributions; Postoperative Period; Qualifying; Recording of previous events; Research; Research Design; Research Methodology; Research Project Grants; Risk; Risk Factors; Sampling; Scientist; Screening procedure; Severities; Societies; Stress; Structure; Surgeon; Surgical complication; Syndrome; Training; Training Programs; Transplant Recipients; Transplantation; Transplantation Surgery; United States National Institutes of Health; Visit; Vulnerable Populations; Waiting Lists; alcohol use disorder; clinical investigation; cognitive function; cognitive testing; cohort; confusion assessment method; dementia risk; end stage liver disease; experience; follow-up; frailty; high risk; improved; indexing; inflammatory marker; lectures; liver transplantation; meetings; modifiable risk; mortality; novel; older patient; optimal treatments; post-transplant; prevent; recruit; response; side effect; stressor; treatment center

PROJECT SUMMARY/ABSTRACT Liver transplantation (LT) is the optimal treatment for individuals with end-stage liver disease (ESLD). Older adults (age≥50) now receive one third of all deceased donor LTs and are at elevated risk for post-LT delirium and cognitive dysfunction due to the stress of surgery, post-LT ICU stay, and immunosuppression. Delirium occurs in 10-47% of LT recipients and is associated with 4-fold higher in-hospital mortality. Delirium is also a risk factor for cognitive decline and Alzheimer’s Disease and related dementias (ADRD). These neurocognitive outcomes are manifestations of an underlying inflammatory state and potentially preventable complications, but no modifiable risk factors have been identified to date among older liver transplant recipients. Frailty, a syndrome conceptualized as the body’s inability to efficiently respond to chronic and acute stressors, is seen in 33% of older LT candidates and is a modifiable state. We developed a validated, LT-specific physical frailty measure [Liver Frailty Index (LFI)] and found that frailty is associated with increased waitlist mortality and post-LT acute rejection. Though mechanistic understanding of these relationships is limited, they might be due to poor reserve and underlying inflammation, the same risk factors underlying delirium, cognitive dysfunction, and ADRD. Therefore, frailty may further increase the risk of delirium, cognitive dysfunction, and ADRD among older recipients. Identifying frailty components and delirium characteristics (length, subtype, severity) associated with increased ADRD risk can inform future research to reduce ADRD among older LT recipients. To investigate the association between pre-LT frailty and post-LT ICU delirium, cognitive dysfunction, and ADRD in older LT recipients, we plan to leverage an ongoing NIA R01-funded multicenter cohort study of older LT recipients to accomplish the following aims: (1) To quantify the association between pre-LT frailty and post- LT ICU delirium among older recipients; (2) To determine whether pre-LT frailty is associated with differences in older recipients’ cognitive function at 3-6 months after LT; and (3) To evaluate the association between pre- LT frailty and post-LT ADRD risk among older recipients. Delirium assessments being performed in the ICU at UCSF will be initiated at Johns Hopkins Hospital (JHH) through the efforts of the trainee. Cognitive dysfunction assessments will be performed post-LT on all participants; Dr. Ruck will perform these assessments at JHH. Our group’s expertise in frailty and delirium in transplantation and utilization of an ongoing longitudinal cohort study make us uniquely able to robustly explore frailty as a predictor of neurocognitive complications including delirium and ADRD in older LT recipients. We hypothesize that frailty is associated with higher risk of post-LT delirium, cognitive dysfunction, and ADRD among older LT recipients. If the proposed aims are achieved, we will improve our ability to identify older recipients at highest risk for delirium, cognitive dysfunction, and ADRD and inform interventions aimed at preventing neurocognitive outcomes in this vulnerable population.

项目摘要/摘要 肝移植（LT）是终末期肝病（ESLD）患者的最佳治疗方法。 现在，成人（年龄≥50）现在接受所有已故捐赠者LT的三分之一是均为风险fost-lt delirum 由于手术的压力，LT ICU停留和免疫抑制而引起的认知功能障碍 发生在10-47％的LT受体中，并且妄想症也高4倍 认知能力下降和阿尔茨海默氏病和相关痴呆症（ADRD）的危险因素 结果是一种基本的炎症状态和可能预防的汇编的表现， 但是，迄今为止，在老年肝移植受者中，没有任何可修改的危险因素。 脆弱的是一种综合征，概念为人体有效反应慢性和急性应激源， 在33％的较旧的LT候选者中可以看到，这是一个条件。 脆弱的措施[肝脏脆弱指数（LFI）]，发现脆弱的候补名单死亡率和 LT急性拒绝。 储备不良和炎症的潜在炎症，del妄，认知功能障碍的相同风险因素， 因此，Adrd。 较老的收件人。 与ADRD风险增加有关，可以为未来的研究提供信息，以减少老年LT接收者的ADRD。 研究前脆弱和LT ICU del妄，认知功能障碍以及 在老年LT接收者中，我们计划利用正在进行的R01资助的多中心队列研究 LT接收者实现以下目的：（1）量化前lt fraity和tost-tof- LT ICU Deliriuum在较旧的配备中 在LT后3-6个月的老年人的认知功能中； 老年接收者中的脆弱和LT ADRD风险。 UCSF将通过受训者的努力在约翰·霍普金斯医院（JHH）启动 将在所有参与者的LT上进行评估； Ruck博士将在JHH进行评估。 我们小组在移植和利用过度纵向队列方面的脆弱和del妄专业知识 研究使我们无权探索作为神经认知并发症的预测指标，包括 老年LT接收者的del妄和adrd。 我们假设脆弱与LT妄想后的风险，认知功能障碍和ADRD有关 在较旧 受到del妄，认知功能障碍和ADRD风险最高的接收者以及针对的信息 防止这种脆弱人群的神经认知结果。

项目成果

Impact of expanding HOPE Act experience criteria on program eligibility for transplantation from donors with human immunodeficiency virus to recipients with human immunodeficiency virus.

扩大 HOPE 法案经验标准对从携带人类免疫缺陷病毒的供体移植到携带人类免疫缺陷病毒的受体的计划资格的影响。

• DOI: 10.1016/j.ajt.2023.03.003
• 发表时间: 2023
• 期刊: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
• 作者: Bowring,MaryG;Ruck,JessicaM;Bryski,MitchellG;Werbel,William;Tobian,AaronAR;Massie,AllanB;Segev,DorryL;Durand,ChristineM
• 通讯作者: Durand,ChristineM

Outcomes of Recipients Aged 65 Years and Older Bridged to Lung Transplant With Extracorporeal Membrane Oxygenation.

65 岁及以上接受者通过体外膜氧合进行肺移植的结果。

• DOI: 10.1097/mat.0000000000002092
• 发表时间: 2024
• 期刊: ASAIO journal (American Society for Artificial Internal Organs : 1992)
• 作者: Zhou,AliceL;Jenkins,ReedT;Ruck,JessicaM;Shou,BenjaminL;Larson,EmilyL;Casillan,AlfredJ;Ha,JinnyS;Merlo,ChristianA;Bush,ErrolL
• 通讯作者: Bush,ErrolL

Perivaccination Antimetabolite Hold and Third Dose of SARS-CoV-2 Vaccine in Lung Transplant Recipients: Preliminary Report.

• DOI: 10.1097/tp.0000000000004240
• 发表时间: 2022-09-01
• 期刊: Transplantation
• 影响因子: 6.2

Kidney Donation After Circulatory Death Using Thoracoabdominal Normothermic Regional Perfusion: The Largest Report of the United States Experience.

使用胸腹常温区域灌注循环死亡后的肾脏捐赠：美国经验的最大报告。

• DOI: 10.1097/tp.0000000000004801
• 发表时间: 2024
• 期刊: Transplantation
• 影响因子: 6.2
• 作者: Zhou,AliceL;Leng,Albert;Ruck,JessicaM;Akbar,ArmaanF;Desai,NirajM;King,ElizabethA
• 通讯作者: King,ElizabethA

Trends in use and three-year outcomes of hepatitis C virus-viremic donor lung transplants for hepatitis C virus-seronegative recipients.

丙型肝炎病毒血清阴性受者丙型肝炎病毒毒血症供体肺移植的使用趋势和三年结果。

• DOI: 10.1016/j.jtcvs.2022.08.019
• 发表时间: 2023
• 期刊: The Journal of thoracic and cardiovascular surgery
• 作者: Ruck,JessicaM;Zeiser,LauraB;Zhou,AliceL;Chidi,AlexisP;Winchester,SophiaL;Durand,ChristineM;Ha,JinnyS;Shah,PaliD;Massie,AllanB;Segev,DorryL;Merlo,ChristianA;Bush,ErrolL
• 通讯作者: Bush,ErrolL