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

项目摘要 这是一项研究，旨在调查酒精使用轨迹与大脑纵向变化之间的关系 功能，以及阿尔茨海默病(AD)的发展。要解决有关 饮酒与阿尔茨海默病的关系，我们将结合血浆Aβ检测和临床测量 对N=600名参与者(年龄为≥50岁，其中17%为非裔美国人)进行的痴呆症持续评估 正在进行的酒精使用障碍研究。我们将利用从圣路易斯遗址收集的样本 酒精中毒遗传学合作研究(COGA)，一项纵向的、基于家庭的酒精使用研究 精神障碍由NIAAA资助30多年，具有广泛的临床，神经心理，电生理， 以及来自受酒精使用障碍影响较大的家庭的基因数据和基于社区的比较 家人。正在进行的对COGA老年参与者的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状态脑电(EEG)和事件相关脑 在认知任务中获得的电位(ERP)(与之前的纵向评估相同)，以及 神经心理调查。结合现有的COGA数据，新的联合评估将允许 创造强有力的酒精使用、大脑功能和神经病理学指标。 这是第一项将AD生物标记物与全面的纵向评估相结合的研究 酗酒。目标1将研究饮酒对临床前AD的影响和临床上的纵向变化 老年人的脑功能和认知能力。目标2将调查遗传、共病、环境和 人口统计学因素缓和了饮酒对AD生物标志物和大脑功能的影响。 这些创新包括集成了最先进的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 在一个已经跟踪了20多年的高风险样本中。这项建议意义重大，因为产品 结果将广泛应用于我们对AD的发展和AD的长期影响的理解 酒精对大脑的影响。

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.