Predicting post-transplant mortality and global functional health based on pre-transplant functional status in liver transplantation

基于肝移植中移植前功能状态预测移植后死亡率和整体功能健康

• 批准号: 10287419
• 负责人: Jennifer C. Lai
• 金额: $ 40.16万
• 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 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10287419
• 关键词: Administrative Supplement; Age; Alzheimer' s disease diagnosis; Alzheimer' s disease diagnostic; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Ammonia; Attention; Biological; Brain; Calcineurin inhibitor; Caregivers; Cirrhosis; Clinical; Cognitive; Coma; Data; Delirium; Detection; Development; Diabetes Mellitus; Diagnosis; Educational Background; Elderly; Ensure; Ethnic Origin; Etiology; Exhibits; Foundations; Future; Gender; General Population; Goals; Guidelines; Health; Hepatic; Hepatic Encephalopathy; High Prevalence; Hour; Hyperlipidemia; Hypertension; Immunosuppression; Impaired cognition; Impairment; Individual; Intervention; Interview; Investigation; Liver; Liver diseases; Magnetic Resonance Imaging; Medical; Metabolic syndrome; Neurocognitive Deficit; Neurologic; Neurologic Symptoms; Neurotoxins; Obesity; Parents; Pathway interactions; Patients; Personality; Phenotype; Physical Function; Population; Postoperative Period; Prevalence; Process; Race; Recording of previous events; Reporting; Research Infrastructure; Risk; Risk Factors; Site; Specialist; Structure; Testing; Time; Transplant Recipients; Transplantation; base; brain health; chronic liver disease; clinical Diagnosis; clinical predictors; cognitive function; cognitive testing; cohort; comorbidity; dementia risk; diagnosis evaluation; disability; frailty; functional status; health assessment; high risk; high risk population; high school; improved; liver function; liver transplantation; mental state; mild cognitive impairment; modifiable risk; mortality; neuroimaging; non-alcoholic fatty liver disease; novel; outcome prediction; physical conditioning; physical inactivity; post-transplant; screening; sedentary lifestyle; stressor; therapy development

PROJECT SUMMARY Cirrhosis is characterized by a spectrum of neurocognitive impairments that is often diagnosed as a single cirrhosis-specific entity, “hepatic encephalopathy”, and considered fully reversible with liver transplantation. But while overt mental status changes often improve within days of transplant, our preliminary data revealed that 18% of liver transplant recipients displayed at least mild cognitive impairment, a precursor for Alzheimer's disease and related dementias (ADRD), at 6 months after transplant, despite normal liver function and an average age of only 58 years. This raises the possibility that some cognitive impairments in cirrhosis are, in fact, not reversible, and potentially represent undiagnosed ADRD and/or elevated risk for ADRD. But at the current time, the prevalence of ADRD in liver transplant patients is neither known nor have the factors contributing to ADRD risk in this population been identified, precluding discussions about risks of post- transplant ADRD and development of risk-reducing interventions. Liver transplant patients have multiple risk factors that increase their risk for ADRD, including contributions from underlying chronic liver disease, high rates of ADRD-related co-morbidities (e.g., hypertension, diabetes), and low education level. Risk for ADRD is further exacerbated after transplant by high rates of delirium and use of long-term immunosuppression. Lastly, frailty, a state that is associated with incident ADRD and shares common biological pathways with ADRD, is highly prevalent in cirrhosis and persists long after transplant. Together, these high-risk factors offer scientific premise for our hypothesis that liver transplant patients have a high prevalence of and risk for ADRD. The overarching goal of our parent R01AG059183 is to investigate the impact of liver transplantation on global functional health as defined by classical geriatric constructs such as physical frailty and disability. The proposed administrative supplement expands this goal by broadening our definition of global functional health from physical to cognitive function, with the intent to identify those with or at risk for ADRD. To accomplish this, we propose a 2-step process involving initial screening/detection followed by ADRD evaluation/diagnosis by a specialist (as recommended by the NIA AD Diagnostic Guidelines). Specifically, using our robust, multi-center research infrastructure, we aim to: 1) characterize the prevalence of and identify clinical predictors of cognitive impairment after liver transplantation using the novel, efficient Brain Health Assessment in a diverse cohort of 350 liver transplant recipients ≥60 years old (since age is a strong ADRD risk factor) across the 5 sites, and 2) conduct detailed cognitive phenotyping (with comprehensive neurologic testing and neuroimaging) in a subset of 15 individuals with cognitive impairment to establish a clinical diagnosis of ADRD and etiologic factors contributing to cognitive impairment. IMPACT: This study will establish a cohort liver transplant recipients with baseline cognitive assessments as the platform for future proposals to investigate longitudinal changes in cognitive function, progression to ADRD, and modifiable ADRD risk factors in this high risk population.

项目概要 肝硬化的特点是一系列神经认知障碍，通常被诊断为单一的神经认知障碍。 肝硬化特有的实体“肝性脑病”，并被认为可以通过肝移植完全逆转。但 虽然明显的精神状态变化通常会在移植后几天内得到改善，但我们的初步数据显示， 18% 的肝移植受者至少表现出轻度认知障碍，这是阿尔茨海默病的先兆 移植后 6 个月时，尽管肝功能正常，并且 平均年龄仅58岁。这提出了肝硬化中某些认知障碍的可能性 事实上，不可逆，并且可能代表未确诊的 ADRD 和/或 ADRD 风险升高。但在 目前，肝移植患者 ADRD 的患病率尚不清楚，也没有相关因素 已确定该人群中 ADRD 风险的贡献因素，排除了有关术后风险的讨论 移植 ADRD 和开发降低风险的干预措施。肝移植患者存在多重风险 增加 ADRD 风险的因素，包括潜在的慢性肝病、高 ADRD 相关合并症（例如高血压、糖尿病）的发生率以及教育水平较低。 ADRD 的风险是 移植后谵妄发生率高和长期免疫抑制的使用进一步加剧了这种情况。最后， 虚弱是一种与 ADRD 事件相关的状态，并且与 ADRD 具有共同的生物学途径， 在肝硬化中非常普遍，并且在移植后持续很长时间。这些高风险因素共同提供了科学依据 我们假设肝移植患者 ADRD 的患病率和风险较高。这 我们母公司 R01AG059183 的总体目标是调查肝移植对全球的影响 功能健康由经典的老年医学概念定义，例如身体虚弱和残疾。这 拟议的行政补充通过扩大我们对全球功能健康的定义来扩展这一目标 从身体功能到认知功能，旨在识别患有 ADRD 或有 ADRD 风险的人。为了实现这一目标， 我们提出了一个两步流程，包括初步筛查/检测，然后由 ADRD 评估/诊断 专家（根据 NIA AD 诊断指南的建议）。具体来说，使用我们强大的多中心 研究基础设施，我们的目标是：1）描述认知的患病率并确定认知的临床预测因素 使用新颖、高效的脑健康评估对不同人群进行肝移植后的损伤 5 个地点的 350 名年龄≥60 岁的肝移植受者（因为年龄是 ADRD 的一个重要危险因素），以及 2) 在一个子集中进行详细的认知表型分析（通过全面的神经系统测试和神经影像学） 对 15 名患有认知障碍的个体进行研究，以建立 ADRD 和病因因素的临床诊断 导致认知障碍。影响：这项研究将建立一个肝移植受者队列 基线认知评估作为未来研究纵向变化的提案的平台 该高危人群的认知功能、ADRD 进展以及可改变的 ADRD 危险因素。