The spectrum of cognitive impairment including Alzheimer’s Disease and Related Dementias after liver transplantation

肝移植后认知障碍的范围，包括阿尔茨海默病和相关痴呆

• 批准号: 10737510
• 负责人: Jennifer C. Lai
• 金额: $ 137.77万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-15 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10737510
• 关键词: Acute; Address; Age; Alcohol consumption; Alzheimer' s disease related dementia; Attention; Biological Markers; Blood Pressure; Brain imaging; Caregivers; Caring; Cessation of life; Chronic; Cirrhosis; Cognition Disorders; Cognitive; Collaborations; Cox Models; Data; Delirium; Dementia; Diabetes Mellitus; Diagnosis; Disease; Dose; Enrollment; Etiology; Exclusion; Foundations; Funding; General Population; Goals; Guidelines; Health; Heavy Drinking; Hepatic Encephalopathy; Hepatology; Hyperammonemia; Hypertension; Immunosuppression; Impaired cognition; Incidence; Infrastructure; Interview; Knowledge; Lewy Bodies; Link; Liver; Liver diseases; Metabolic syndrome; Nested Case-Control Study; Neurobehavioral Manifestations; Neurocognitive; Neurologic; Organ Transplantation; Outcome; Participant; Pathway interactions; Patient Care; Patient Outcomes Assessments; Patients; Personal Satisfaction; Pilot Projects; Plasma; Population; Practice Guidelines; Prevalence; Protocols documentation; Recommendation; Research; Research Design; Research Personnel; Risk Factors; Role; Site; Solid; Specialist; Stress; Structure; Testing; Time; Transplant Recipients; Transplantation; United States National Institutes of Health; Vascular Dementia; Visit; brain magnetic resonance imaging; cognitive function; cognitive testing; cohort; comorbidity; dementia risk; experience; frailty; improved; insight; liver transplantation; mixed dementia; neuropsychiatry; novel; postoperative delirium; premature; prospective; screening; sex; survival prediction; tool

PROJECT SUMMARY Our highly successful multi-center Functional Assessment in Liver Transplantation (FrAILT) Study, funded by the NIH since 2013, has definitively characterized physical frailty in patients with cirrhosis undergoing liver transplantation (LT) and provided the foundation to codify physical frailty assessment through national guidelines for cirrhosis/LT patient management. As we closed the knowledge gap around physical frailty, we identified a new gap in LT patients—cognitive “frailty”, or more precisely, the manifestation of cognitive impairment. In 2 pilot studies, we found that 30-60% of LT recipients met criteria for cognitive impairment. Yet, currently, the spectrum of post-LT cognitive impairment—from subtle attentional changes to Alzheimer’s Disease and Related Dementias (ADRD)—is not well characterized. As a result, clinicians do not screen for cognitive impairment in the post-LT setting, and LT patients are not referred to specialists for timely diagnosis/management. In this competing renewal, we will leverage our multi-center FrAILT Study to address this unmet need. We hypothesize that LT patients experience premature cognitive syndromes, including ADRD, after LT (relative to the general population), that cognitive impairment impacts post-LT global functional health, and that physical frailty is a major predictor of post-LT cognitive impairment. There is strong scientific premise for these hypotheses, as many risk factors for cirrhosis are linked with cognitive impairment. These include common ADRD comorbidities (e.g., diabetes, hypertension), heavy alcohol use, hepatic encephalopathy, post-LT delirium, and immunosuppression. Physical frailty itself, prevalent in LT patients, shares common pathways with ADRD. The scientific goal of this competing renewal is to deeply characterize the spectrum of cognitive impairment including ADRD in post-LT patients. To accomplish this, we will extend the FrAILT Study at 6 U.S. sites and expand our assessment protocol with neurocognitive screening in ~2,000 post-LT FrAILT patients. Additionally, we will establish new “neuro- hepatology” collaborations with 5 of our sites’ AD Research Centers (ADRC) to conduct deep cognitive profiling—through comprehensive neurocognitive assessments and brain imaging—in 150 post-LT patients who display cognitive impairment. Specifically, we aim to: 1) Characterize the prevalence/incidence of and identify factors associated with post-LT cognitive impairment and evaluate its association with post-LT global functional health; 2) Characterize trajectories of cognitive function in the first year post-LT; 3) conduct deep cognitive profiling to differentiate among the etiologies of dementia. Our established multi-center FrAILT Study is uniquely poised to address this enormous unmet need for deep characterization of cognitive impairment in LT patients who have a high burden of conventional ADRD risks but have traditionally been excluded from ADRD studies. Further, we will develop a novel cohort with rich cognitive data that may yield novel insights into liver- and transplant-related contributors to ADRD in other (general, solid organ transplant) populations.

项目总结 我们非常成功的肝移植多中心功能评估(FrAILT)研究，由 自2013年以来，美国国立卫生研究院明确描述了肝硬变患者的身体虚弱。 移植(LT)，并为通过国家指南编纂身体虚弱评估提供了基础 用于肝硬变/肝移植患者管理。随着我们弥合关于身体脆弱的知识鸿沟，我们发现了一个 LT患者的新差距--认知“脆弱”，或者更准确地说，是认知障碍的表现。在2个试点中 研究发现，30-60%的LT接受者符合认知障碍的标准。然而，目前，频谱 肝移植后认知损害--从细微的注意力变化到阿尔茨海默病及其相关 痴呆症(ADRD)-没有得到很好的描述。因此，临床医生不对患者进行认知障碍筛查 肝移植后的设置，以及肝移植患者没有被转介到专家那里进行及时的诊断/治疗。在这 为了竞争更新，我们将利用我们的多中心FrAILT研究来满足这一未得到满足的需求。我们假设 LT患者在LT后会经历包括ADRD在内的过早认知综合征(相对于一般的 人群)，认知障碍影响移植后的全球功能健康，身体虚弱是一个主要的 肝移植术后认知功能障碍的预测因子。这些假设有很强的科学前提，因为许多风险 肝硬变的因素与认知障碍有关。这些包括常见的ADRD并存(例如， 糖尿病、高血压)、酗酒、肝性脑病、肝移植术后精神错乱和免疫抑制。 在LT患者中普遍存在的身体虚弱本身与ADRD具有共同的途径。它的科学目标是 竞争性更新是为了深刻描述包括肝移植后ADRD在内的认知障碍的特征 病人。为了实现这一目标，我们将在美国6个地点扩展FrAILT研究，并扩展我们的评估方案 对约2,000名LT后FrAILT患者进行神经认知筛查。此外，我们还将建立新的“神经-- 《肝病》与我们网站的5个AD研究中心(ADRC)合作进行深度认知 通过全面的神经认知评估和脑成像对150名肝移植术后患者进行简写 表现出认知障碍。具体地说，我们的目标是：1)描述风湿性心脏病的流行/发病率，并确定 肝移植后认知损害的相关因素及其与肝移植后整体功能的关系 健康；2)描述术后第一年的认知功能轨迹；3)进行深层认知 鉴别痴呆症病因的侧写法。我们建立的多中心FrAILT研究是独一无二的 准备解决这一巨大的未得到满足的需求，以深入描述LT患者的认知障碍 他们有很高的传统ADRD风险负担，但传统上被排除在ADRD研究之外。 此外，我们将开发一个具有丰富认知数据的新队列，可能会产生对肝脏的新见解--以及 其他(一般的、实体器官移植)人群中与移植相关的ADRD的贡献者。

项目成果

The 5Ms of Geriatrics in Gastroenterology: The Path to Creating Age-Friendly Care for Older Adults With Inflammatory Bowel Diseases and Cirrhosis.

• DOI: 10.14309/ctg.0000000000000445
• 发表时间: 2022-01-12
• 期刊: Clinical and translational gastroenterology
• 影响因子: 3.6
• 作者: Kochar B;Ufere NN;Ritchie CS;Lai JC
• 通讯作者: Lai JC

Outcomes of Liver Transplantation Among Older Recipients With Nonalcoholic Steatohepatitis in a Large Multicenter US Cohort: the Re-Evaluating Age Limits in Transplantation Consortium.

• DOI: 10.1002/lt.25863
• 发表时间: 2020-11
• 期刊: Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society
• 作者: Kwong AJ;Devuni D;Wang C;Boike J;Jo J;VanWagner L;Serper M;Jones L;Sharma R;Verna EC;Shor J;German MN;Hristov A;Lee A;Spengler E;Koteish AA;Sehmbey G;Seetharam A;John N;Patel Y;Kappus MR;Couri T;Paul S;Salgia RJ;Nhu Q;Frenette CT;Lai JC;Goel A;Re-Evaluating Age Limits in Transplantation (REALT) Consortium
• 通讯作者: Re-Evaluating Age Limits in Transplantation (REALT) Consortium

Perioperative Delta Sodium and Post-Liver Transplant Neurological Complications in Liver Transplant Recipients.

肝移植受者围手术期 Delta 钠和肝移植后神经并发症。

• DOI: 10.1097/tp.0000000000004102
• 发表时间: 2022
• 期刊: Transplantation
• 影响因子: 6.2
• 作者: Berry,Kacey;Copeland,Timothy;Ku,Elaine;Lai,JenniferC
• 通讯作者: Lai,JenniferC

Psychological contributors to the frail phenotype: The association between resilience and frailty in patients with cirrhosis.

• DOI: 10.1111/ajt.16131
• 发表时间: 2021-01
• 期刊: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
• 作者: Wong RJ;Mohamad Y;Srisengfa YT;Kent DS;Seetharaman S;Shah RJ;Lai JC
• 通讯作者: Lai JC

Symptom Burden Is Associated with Increased Emergency Department Utilization among Patients with Cirrhosis.

症状负担与肝硬化患者急诊科使用率的增加有关。

• DOI: 10.1089/jpm.2021.0219
• 发表时间: 2022
• 期刊: Journal of palliative medicine
• 影响因子: 2.8
• 作者: Deng,LisaX;Kent,DorotheaS;O'Riordan,DavidL;Pantilat,StevenZ;Lai,JenniferC;Bischoff,KaraE
• 通讯作者: Bischoff,KaraE