Investigating the longitudinal relationship between alcohol use, neurophysiological functioning, and Alzheimer disease biomarkers in the Collaborative Study on the Genetics of Alcoholism

在酒精中毒遗传学合作研究中调查饮酒、神经生理功能和阿尔茨海默病生物标志物之间的纵向关系

• 批准号: 10660983
• 负责人: Sarah Hartz
• 金额: $ 39.38万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-20 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10660983
• 关键词: Address; Adult; Affect; African American; Age; Alcohol consumption; Alcoholic beverage heavy drinker; Alcohols; Alleles; Alzheimer disease detection; Alzheimer' s Disease; Alzheimer' s disease risk; Alzheimer’s disease biomarker; Amyloid beta-Protein; Apolipoprotein E; Auditory; Blood Tests; Brain; Brain Pathology; Brain region; Clinical; Cognition; Communities; Complex; Data; Dementia; Demographic Factors; Development; Disease; Education; Elderly; Electroencephalography; Electrophysiology (science); Environmental Risk Factor; Evaluation; Event; Family; Funding; Genes; Genetic; Heavy Drinking; Impaired cognition; Knowledge; Light; Longitudinal Studies; Measurement; Measures; National Institute on Alcohol Abuse and Alcoholism; Nerve Degeneration; Neuropsychology; Onset of illness; Participant; Pattern; Phase; Plasma; Process; Psychopathology; Public Health; Research Personnel; Rest; Sampling; Semantics; Site; Span 20; Surveys; Testing; Visual; abeta deposition; age related; aging brain; alcohol effect; alcohol use disorder; cognitive task; comorbidity; demographics; design; drinking; genetic risk factor; genetics of alcoholism; high risk; imaging study; innovation; insight; member; mortality; neural; neural network; neuropathology; neurophysiology; neurotoxic; polygenic risk score; pre-clinical; protective factors; recruit; sample collection; structural imaging; substance use

Project Summary This is a study to investigate the relationship between trajectories of alcohol use, longitudinal changes in brain function, and the development of Alzheimer disease (AD). To address gaps in knowledge about the relationship between alcohol use and AD, we will integrate plasma Aβ testing and a measurement of clinical dementia into ongoing assessments of N=600 participants (age ≥ 50, 17% African American) in a large ongoing study of alcohol use disorder. We will leverage sample collection from the St. Louis site of the Collaborative Study on the Genetics of Alcoholism (COGA), a longitudinal, family-based study of alcohol use disorder funded by NIAAA for over 30 years, with extensive clinical, neuropsychological, electrophysiological, and genetic data from families densely affected by alcohol use disorder and community-based comparison families. The ongoing assessments of older COGA participants includes a comprehensive evaluation of alcohol use, neurophysiological measures including resting-state electroencephalogram (EEG) and event-related brain potentials (ERPs) acquired during cognitive tasks (same as in previous longitudinal assessments), and neuropsychological surveys. Together with existing COGA data, the new combined assessment will allow for creation of powerful measures of alcohol use, brain function, and neuropathology. This represents the first study to integrate AD biomarkers with comprehensive, longitudinal assessments of alcohol use. Aim 1 will examine the effect of alcohol consumption on preclinical AD and longitudinal changes in brain function and cognition in older adults. Aim 2 will investigate genetic, comorbid, environmental, and demographic factors as moderating the effect of alcohol consumption on AD biomarkers and brain function. The innovations include integration of state-of-the-art AD assessment, plasma biomarker of AD, brain function measures of neural synchronicity and connectivity, and comprehensive longitudinal assessment of alcohol use in a high-risk sample that has been followed over 20 years. This proposal is significant because the products and results will apply broadly to our understanding of both the development of AD and the long-term impact of alcohol on the brain.

项目摘要 本研究旨在探讨酒精使用轨迹、大脑纵向变化和大脑皮质的变化之间的关系。 功能，以及阿尔茨海默病（AD）的发展。为了弥补在以下方面的知识空白： 酒精使用与AD之间的关系，我们将整合血浆Aβ检测和临床 在一个大规模的研究中，对N=600名参与者（年龄≥ 50岁，17%为非洲裔美国人）进行持续评估， 正在进行的酒精使用障碍研究。我们将利用从圣路易斯网站收集的样本， 酒精中毒遗传学合作研究（COGA），一项以家庭为基础的酒精使用纵向研究 由NIAAA资助30多年的疾病，具有广泛的临床、神经心理学、电生理学， 以及来自受酒精使用障碍影响严重的家庭的遗传数据和基于社区的比较 家庭对老年COGA参与者的持续评估包括对酒精的全面评估 使用、神经生理学测量，包括静息态脑电图（EEG）和事件相关脑 在认知任务期间获得的电位（ERP）（与先前的纵向评估相同），以及 神经心理学调查与现有的COGA数据一起，新的综合评估将允许 创建酒精使用，大脑功能和神经病理学的强有力措施。 这是第一项将AD生物标志物与AD的综合纵向评估相结合的研究。 饮酒目的1将检查饮酒对临床前AD的影响以及 老年人的大脑功能和认知能力。目标2将研究遗传、共病、环境和 人口统计学因素作为调节酒精消费对AD生物标志物和脑功能的影响。 这些创新包括整合最先进的AD评估、AD的血浆生物标志物、脑功能 神经同步性和连接性的测量，以及酒精使用的综合纵向评估 在一个高风险的样本中，已经被跟踪了20多年。这一建议意义重大，因为产品 结果将广泛适用于我们对AD发展和长期影响的理解。 酒精对大脑的影响