Role of Liver Fibrosis in Cognitive Impairment and Dementia

肝纤维化在认知障碍和痴呆中的作用

基本信息

批准号：
10282845
负责人：
Neal S Parikh
金额：
$ 19.49万
依托单位：
WEILL MEDICAL COLL OF CORNELL UNIV
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-01 至 2026-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10282845
关键词：
Abeta clearance Address Adult Affect Age-Years Age-associated memory impairment Alcohol consumption Alcohols Alzheimer&apos s disease related dementia American Analysis of Covariance Ancillary Study Area Atherosclerosis Risk in Communities Biological Markers Blood Vessels Brain Brain imaging Cardiovascular Diseases Cerebrovascular Trauma Characteristics Clinic Clinical Cognition Cognitive Data Dementia Enrollment Epidemiology Etiology Extracellular Matrix Familiarity Fibrosis Future Gap Junctions General Population Goals Gold Health Hepatic Encephalopathy Hepatology Hippocampus (Brain)Human Image Impaired cognition Internal Medicine Iron K-Series Research Career Programs Laboratories Linear Regressions Link Liver Liver Dysfunction Liver Fibrosis Liver diseases Logistic Regressions Magnetic Resonance Imaging Measures Memory Disorders Memory impairment Mentors Mentorship Metabolic syndrome Methods Modeling National Institute of Neurological Disorders and Stroke Neurologic Neurologist Neurology Neuropsychological Tests Outcome Participant Pathologic Pathway interactions Patients Peripheral Pharmaceutical Preparations Population Positioning Attribute Prevalence Preventive Prospective cohort study Proteins Public Health Research Research Design Research Personnel Risk Factors Role Sampling Studies Standardization Statistical Methods Systemic disease Testing Therapeutic Training United Kingdom United States National Institutes of Health Virus Diseases White Matter Hyperintensity Work abeta deposition adjudicate apolipoprotein E-4 base biobank brain health brain volume career chronic liver disease chronic liver injury cognitive performance cohort dementia risk elastography hazard imaging biomarker innovation insight liver metabolism mild cognitive impairment multidisciplinary nervous system disorder neuroimaging neuroimaging marker non-demented novel novel therapeutic intervention patient oriented research prospective public health relevance recruit response screening secondary analysis skills symposium tomography tool uptake β-amyloid burden

项目摘要

PROJECT SUMMARY/ABSTRACT This is a K23 career development award application for Dr. Neal Parikh, a neurologist and junior investigator pursuing patient-oriented research on the contribution of liver fibrosis to cognitive impairment and dementia. Dr. Parikh seeks to develop expertise in two key content areas: 1) cognitive impairment and Alzheimer’s disease and related dementias (ADRD), with a focus on neuroimaging correlates of ADRD and mechanisms of cognitive impairment, and 2) chronic liver disease hepatology with a focus on liver fibrosis and biomarkers. He also seeks to develop advanced skills in study design and statistical methods specific to the study of ADRD. Dr. Parikh has assembled a mentoring team led by Dr. Costantino Iadecola, a neurologist with expertise in the links between systemic factors and cognition, in addition to three co-mentors: Dr. David E. Cohen, a hepatologist with expertise in chronic liver disease and liver metabolism, Dr. Mony de Leon, an investigator with expertise in ADRD neuroimaging, and Dr. Rebecca Gottesman, a neurologist with expertise in ADRD epidemiology. Based on emerging evidence and his preliminary data, Dr. Parikh’s central hypothesis is that liver fibrosis is independently associated with cognitive impairment, dementia, and related neuroimaging markers. Dr. Parikh will test this hypothesis in three specific aims. Specific Aim 1 will test the hypothesis that liver fibrosis is associated with cognitive impairment, incident dementia risk, and related imaging markers at the population level among 500,000 participants in the United Kingdom Biobank prospective cohort study. Specific Aim 2 will test the hypothesis that liver fibrosis is associated with cortical β-amyloid deposition on florbetapir position emission tomography (PET) imaging in a diverse, multi-center cohort of 346 nondemented participants in an Atherosclerosis Risk in Communities-PET ancillary study. Specific Aim 3 will characterize the prevalence, causes, and impact of subclinical liver fibrosis in a prospectively enrolled cohort of 120 patients with cognitive impairment and dementia. The proposed aims will use multiple liver fibrosis markers and complementary cognitive endpoints, spanning neuropsychological testing, adjudicated incident dementia outcomes, and neuroimaging markers including white matter hyperintensity volume and cortical β-amyloid burden. The proposed research is significant because it seeks to establish a novel risk factor for cognitive impairment and dementia, thus raising the possibility of new liver-targeted preventive and therapeutic strategies in ADRD and cognitive impairment broadly. The proposed research is innovative because it seeks to expand the paradigm of multi-etiology cognitive impairment and dementia by establishing a role for liver fibrosis in cognition beyond hepatic encephalopathy. Further, this work will bridge hepatology and neurology to address the burden of neurological disease by adapting contemporary and nascent hepatology tools to neurological research.

项目摘要/摘要这是K23职业发展奖的申请，纳尔·帕里克（Neal Parikh）研究肝纤维化对认知障碍和的贡献的研究人员失智。 Parikh博士试图在两个关键内容领域发展专业知识：1）认知障碍和阿尔茨海默氏病和相关痴呆症（ADRD），重点是ADRD和认知障碍的机制和2）慢性肝病肝病，重点是肝纤维化和生物标志物。他还寻求发展研究设计和特定于统计方法的高级技能 ADRD的研究。 Parikh博士已经组建了一个由Costantino Iadecola博士领导的心理团队，他是除了三个联席会员外，全身因素与认知之间的联系方面的专业知识：David E.博士科恩（Cohen），一名具有慢性肝病和肝脏代谢专业知识的肝病学家，Mony de Leon博士具有ADRD神经影像学专业知识的研究者，以及具有专业知识的神经科医生丽贝卡·戈特斯曼（Rebecca Gottesman）博士 ADRD流行病学。根据新兴的证据和他的初步数据，帕里克博士的中心假设是肝纤维化与认知障碍，痴呆和相关神经成像独立相关标记。 Parikh博士将以三个具体目标检验这一假设。具体目标1将检验以下假设肝纤维化与认知障碍，入射痴呆风险和相关成像标记有关英国生物银行前瞻性队列研究中有500,000名参与者的人口水平。具体的 AIM 2将检验以下假设：肝纤维化与Florbetapir上的皮质β-淀粉样蛋白沉积有关在潜水员，多中心队列中的346个无需参与者的位置排放层析成像（PET）成像在社区-PET辅助研究中的动脉粥样硬化风险中。特定目标3将表征患病率，在120例认知患者中，亚临床肝纤维化的原因和亚临床肝纤维化的影响障碍和痴呆症。拟议的目标将使用多个肝纤维化标记和完成认知终点，跨越神经心理学测试，调整后的痴呆症结果和神经影像标记，包括白质高强度体积和皮质β-淀粉样蛋白伯恩。这拟议的研究很重要，因为它试图为认知障碍和痴呆症，从而增加了在ADRD和认知障碍广泛。拟议的研究具有创新性，因为它试图扩大通过确定肝纤维化在认知中的作用，多性认知障碍和痴呆肝脑病。此外，这项工作将弥合肝病学和神经病学，以解决神经系统疾病是通过将当代和新生的肝病工具改编成神经系统研究的。