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.

项目总结