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.

项目摘要 肝硬化的特征是一系列神经认知障碍，通常被诊断为单一障碍 肝硬化特异性实体，“肝脑病”，并被视为完全可通过肝移植的可逆性。 尽管公开的心理状况变化通常在移植后几天内有所改善，但我们的初步数据表明 18％ 疾病和相关痴呆症（ADRD），在移植后6个月，Dospite正常肝功能和A 平均年龄仅为58岁。这增加了肝硬化中某些认知障碍的可能性 事实，不可逆，并且有可能代表未诊断的ADRD和/或ADRD风险升高。但是在 当前时间，肝移植患者ADRD的患病率既不知道也不是因素 确定了在该人群中导致ADRD风险的贡献，从而排除了有关后风险的讨论 移植ADRD和降低风险干预措施的发展。肝移植患者有多种风险 增加其ADRD风险的因素，包括慢性肝病的潜在贡献，高 与ADRD相关的合并症（例如高血压，糖尿病）和低教育水平的率。 ADRD的风险是 通过高del妄率和长期免疫抑制的使用率进一步加剧了移植后。最后， 脆弱的状态与事件相关并与ADRD共享常见的生物学途径，是 在移植后很长时间以来，在肝硬化和持续很长时间中很普遍。这些高风险因素共同提供了科学的因素 我们的假设是肝移植患者的ADRD患病率很高和风险。 我们父母R01AG059183的总体目标是研究肝移植对全球的影响 由经典的老年构建体（例如身体上的脆弱和残疾）定义的功能健康。这 拟议的行政补品通过扩大我们对全球功能健康的定义扩大了这一目标 从身体到认知功能，目的是确定患有ADRD或有风险的人。为此， 我们提出了一个两步过程，涉及初始筛查/检测，然后通过ADRD评估/诊断 专家（根据NIA AD诊断指南的建议）。特别是使用我们强大的多中心 研究基础设施，我们的目标是：1）表征并确定认知的临床预测因子 肝移植后使用新颖，有效的大脑健康评估在多样性队列中的损伤 350名肝移植接受者≥60岁（由于年龄是强大的ADRD风险因素），而2个地点2） 在子集中进行详细的认知表型（具有全面的神经系统测试和神经影像学） 在15名认知障碍的人中，建立了ADRD和病因学因素的临床诊断 导致认知障碍。影响：这项研究将与 基线认知评估是未来提案的平台，以调查纵向变化 在这个高风险人群中，认知功能，向ADRD的发展以及可修改的ADRD风险因素。