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.

项目概要 这是一项研究酒精使用轨迹与大脑纵向变化之间关系的研究 功能和阿尔茨海默病（AD）的发展。为了解决有关知识的空白 酒精使用与 AD 之间的关系，我们将整合血浆 Aβ 测试和临床测量 痴呆症纳入对 N=600 名参与者（年龄 ≥ 50 岁，17% 为非洲裔美国人）的持续评估 正在进行的酒精使用障碍研究。我们将利用来自圣路易斯网站的样本收集 酒精中毒遗传学合作研究 (COGA)，一项基于家庭的纵向酒精使用研究 该疾病由 NIAAA 资助超过 30 年，具有广泛的临床、神经心理学、电生理学、 受酒精使用障碍严重影响的家庭的遗传数据和社区比较 家庭。对老年 COGA 参与者的持续评估包括对酒精的综合评估 使用、神经生理学测量，包括静息态脑电图 (EEG) 和事件相关大脑 在认知任务期间获得的潜力（ERP）（与之前的纵向评估相同），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的测量方法。 这是第一项将 AD 生物标志物与全面、纵向评估相结合的研究 酒精的使用。目标 1 将检查饮酒对临床前 AD 的影响以及纵向变化 老年人的大脑功能和认知。目标 2 将调查遗传、共病、环境和 人口因素可调节饮酒对 AD 生物标志物和大脑功能的影响。 这些创新包括整合最先进的 AD 评估、AD 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 在一个已经跟踪了 20 多年的高风险样本中。该提案意义重大，因为产品 结果将广泛应用于我们对 AD 发展及其长期影响的理解 酒精对大脑的影响。