Spectrum of Neuro-Cognitive Impairment in Cirrhosis

肝硬化神经认知障碍的范围

• 批准号: 8233977
• 负责人: Jasmohan S Bajaj
• 金额: $ 39.94万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8233977
• 关键词: Accidents; Activities of Daily Living; Affect; Attention; Automobile Driving; Brain; Brain imaging; Cause of Death; Cirrhosis; Clinical; Cognition; Cognitive; Complication; Data; Defect; Deterioration; Development; Diagnosis; Diagnostic; Diffusion Magnetic Resonance Imaging; Evaluation; Functional Imaging; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Health; Hepatic Encephalopathy; Hospitalization; Impaired cognition; Impairment; Individual; Intervention; Knowledge; Liver; Liver diseases; Magnetic Resonance Spectroscopy; Measures; Medical; Metabolic; Methodology; Methods; Modeling; Morbidity - disease rate; Neurons; Outcome; Patient Selection; Patients; Physiological; Physiology; Portal Hypertension; Procedures; Psyche structure; Quality of life; Recording of previous events; Severities; Socioeconomic Status; Syndrome; System; Techniques; Testing; Therapeutic; Time; Transplantation; United States National Institutes of Health; Work; base; clinically relevant; cognitive change; cognitive function; high risk; impaired driving performance; improved; liver transplantation; mental state; mortality; psychosocial; public health relevance; response; skills; social; vehicular accident

DESCRIPTION (provided by applicant): Hepatic encephalopathy (HE) is a neuro-cognitive complication of cirrhosis that is divided into the clinically apparent overt HE (OHE), or minimal HE (MHE), which requires cognitive testing. MHE is associated with poor quality of life (QOL), impaired driving skills, and high risk of OHE development. Criteria used to categorize cirrhotics into normal, MHE and OHE are subjective and not reproducible. This subjectivity and lack of correlation with clinically relevant outcomes is a major gap in our knowledge. Since HE is a continuum, a more productive approach may be to quantify it using continuous measures that locate the patient within the spectrum of neuro-cognitive impairment in cirrhosis (SONIC). Such an approach would allow quantitative assessment in cognitive changes following progression of liver disease, as well as improvement in response to liver transplant (LT). Our central hypothesis is: In subjects with cirrhosis, the degree of impairment and the rate of deterioration of neuro-cognitive function, predicts development of (1) overt hepatic encephalopathy (2) hepatic encephalopathy-related medical and psychosocial outcomes and (3) reversibility of neuro-cognitive course after liver transplant. The specific aims include: (1) Develop a model of SONIC to predict the HE-related medical and psycho-social outcomes in cirrhosis. 300 cirrhotics without OHE will undergo testing with a multi-dimensional cognitive battery, driving history, socio- economic status and QOL. These will be repeated every 6 months until the primary endpoint of OHE development. Hospitalization, accidents, QOL and socio-economic status will be secondary endpoints. The hypothesis is that a multi-dimensional cognitive model will provide a sensitive and specific method of quantifying SONIC that will (a) predict OHE and hospitalization development, and (b) quantify impairment in quality of life, driving and socio-economic status. (2) Define the impact of liver transplant on SONIC and to determine patho-physiological factors that modulate reversibility of cognitive dysfunction after liver transplant: 45 patients on the transplant list will undergo SONIC testing prior to, and at six and twelve months post-LT. The impact of pre-LT cognitive dysfunction severity and MR assessment (MR spectroscopy, diffusion-tensor imaging and functional MR) on reversibility of SONIC after LT will also be defined. The hypothesis is that pre-LT cognitive dysfunction severity and its underlying patho-physiology determines the degree of reversibility post-LT. This contribution is significant as it is expected to engender a paradigm shift in the evaluation of cognition in cirrhosis by integrating an objective approach to predict medical and psycho-social outcomes, and by defining the impact of transplant on cognition. Such results will have a positive impact, because it will introduce objectivity into this field and define the patho-physiology as well as cognitive outcome of SONIC after transplant. This would improve diagnostic and therapeutic strategies for cognitive testing in cirrhosis as well as improve patient selection for transplant. PUBLIC HEALTH RELEVANCE: The proposed studies will change the way patients with cirrhosis are approached and will replace the current faulty system of categorizing their brain function with a better method of predicting how the effect of cirrhosis on the brain affect patients' medical outcomes as well as their quality of life and ability to work and earn and how much of these defects change after liver transplant. These procedures will then make it easier for doctors to diagnose, predict complications and treat patients with cirrhosis. Thus, the findings are ultimately expected to be applicable in improving the health of patients with cirrhosis, which is one of the leading causes of death.

描述（由申请人提供）：肝性脑病（HE）是肝硬化的神经认知并发症，被分为临床明显的公开He（OHE），或者最小的He（MHE），需要认知测试。 MHE与生活质量差（QOL），驾驶技能受损以及OHE开发的高风险有关。用来将cirhotics分类为正常的标准，MHE和OHE是主观的，不可再现。在我们所知，这种主观性和与临床相关结果缺乏相关性是一个主要差距。由于他是连续性，因此一种更有生产力的方法可能是使用连续措施将患者定位在肝硬化（Sonic）中的神经认知障碍范围内。这种方法将允许肝病进展后认知变化的定量评估，并响应肝脏移植（LT）的改善。我们的中心假设是：在患有肝硬化的受试者中，神经认知功能的损害程度和恶化率可以预测（1）（1）公开的肝性脑病（2）肝性脑病相关的医学和心理社会疾病的疾病，以及（3）神经认知的可逆性，后来可依靠liver liver liver liver liver liver liver liver liver liver liver liver liver liver liver liverliver river river river river river river river river river river river river inversibal in liverliver saftplant shecephalopatic（2）。具体目的包括：（1）开发一种声音模型，以预测肝硬化中与HE相关的医学和心理社会结局。 300没有OHE的CIRRHOTICS将通过多维认知电池，驱动历史，社会经济状况和质量检查进行测试。这些将每6个月重复一次，直到OHE开发的主要终点为止。住院，事故，QOL和社会经济地位将是次要终点。假设是，多维认知模型将提供一种量化声音的敏感和特定的方法，该方法将（a）预测OHE和住院发展，以及（b）量化生活质量，驾驶和社会经济状况的损害。 （2）定义肝脏移植对声音的影响，并确定病态生理因素，以调节肝移植后认知功能障碍的可逆性：移植列表中的45例患者将在LET之前进行Sonic测试，并在LT后六个月和十二个月进行。还将定义前LT认知功能障碍严重程度和MR评估（MR光谱，扩散诱变成像和功能性MR）对LT后Sonic可逆性的影响。假设是，前LT认知功能障碍严重程度及其基本的病理学决定了LT后可逆性的程度。这种贡献很重要，因为预计通过整合一种预测医学和心理社会结局的客观方法，并定义移植对认知对认知的影响，这将导致对肝硬化认知评估的范式转移。这样的结果将产生积极的影响，因为它会将客观性引入该领域，并定义了移植后声波的病理生理学以及认知结果。这将改善用于肝硬化认知测试的诊断和治疗策略，并改善患者选择移植。 公共卫生相关性：拟议的研究将改变肝硬化患者的接近患者的方式，并通过更好地预测肝硬化对大脑的影响如何影响患者的医疗结果以及他们的生活质量，工作能力和工作能力以及这些缺陷后，这些缺陷在肝脏移植后会发生多大变化。然后，这些程序将使医生更容易诊断，预测并发症和治疗肝硬化患者。因此，最终预计这些发现适用于改善肝硬化患者的健康，这是死亡的主要原因之一。