Ethanol-metabolizing genes and the relationship between ethanol intake and cognitive decline

乙醇代谢基因以及乙醇摄入与认知能力下降之间的关系

• 批准号: 9272725
• 负责人: Shelly-Ann M Love
• 金额: $ 3.56万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-02 至 2019-05-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9272725
• 关键词: Acetaldehyde; Adult; Affect; African American; Age; Age-associated memory impairment; Alcohol consumption; Alleles; Alzheimer' s Disease; Ancillary Study; Apolipoprotein E; Applications Grants; Atherosclerosis Risk in Communities; Behavioral; Benefits and Risks; Classification; Cognition; Data; Dementia; Education; Elderly; Epidemiology; Ethanol; Ethanol Metabolism; Fellowship; Genes; Genetic; Genetic Polymorphism; Genetic Predisposition to Disease; Genetic Variation; Genotype; Goals; Health; Health Care Costs; Heavy Drinking; High Prevalence; Impaired cognition; Incidence; Intake; Intercept; Linear Regressions; Link; Love; Measurement; Measures; Mentors; Methods; Minor; Modeling; Modification; Neurocognitive; North Carolina; Participant; Population; Population Heterogeneity; Predisposition; Prevalence; Process; Public Health; Race; Randomized; Reporting; Research; Research Design; Research Personnel; Resources; Risk; Risk Factors; Role; Single Nucleotide Polymorphism; Smoking Status; Students; Time; Training; Universities; Variant; Woman; aging population; alcohol effect; alcohol measurement; base; cognitive function; cognitive testing; cohort; design; disability; drinking; follow-up; gene environment interaction; innovation; men; middle age; multidisciplinary; oxidation; population based; population stratification; pre-doctoral; prevent; sex

Abstract This pre-doctoral fellowship (F31) grant application is designed to promote the training of Shelly-Ann Love, a pre-doctoral student in the Department of Epidemiology at the University of North Carolina. Her goal is to become an independent researcher who conducts innovative, translational health research. During the F31 training the applicant will be mentored by her sponsors Drs. Kari North and Gerardo Heiss. The topic of the proposed research is a multidisciplinary assessment of the role of ethanol intake in age-related cognitive decline, as modified by genetic susceptibility. Because of the increasing number of older adults the prevalence of dementia will quadruple from 5.2 million to 16 million by 2050, with an expected increase of healthcare cost from $203 billion to $1.2 trillion. Studies of the association of ethanol intake with cognitive decline and dementia have yielded inconsistent findings, likely attributable to a reliance on a single measurement of ethanol intake, non-standardized definitions of cognitive decline, outdated classifications of dementia, short follow-up times, and or lack of analytic control of confounders and effect measure modifiers. Few studies investigated the effects of ethanol intake in black populations despite the higher prevalence, incidence, and cumulative risk of Alzheimer's dementia in blacks compared to whites. Importantly, no study has investigated the effects of ethanol intake on cognition from mid-life to older adulthood. Further, variation within ethanol- metabolizing genes alters the rate of ethanol oxidation, yet few studies have evaluated effect measure modification of the ethanol intake-cognitive decline relationship by genetic variation in ancestrally diverse populations. Thus, studies based on diverse populations with repeated measurements of ethanol intake and cognitive function that have been genotyped for ethanol-metabolism SNPs are needed to better understand the relationship of ethanol intake with cognitive decline. These aims will be met through the training proposed in this application and the doctoral research based on the bi-racial, population-based Atherosclerosis Risks in Communities (ARIC) cohort of 12,773 black and white adults between the ages of 45-64 years at intake. Analyses will include repeated measurements on participants who attended 5 examinations over 20 years of follow-up. This research responds to a need to identity susceptibility and modifiable behavioral factors that might prevent, or delay the progression of cognitive decline and dementia. The potential impact of the study is its ability to contribute new information on the putative effects of ethanol intake on cognitive decline, and the potential public health risks and benefits of ethanol intake.

抽象的 此博士前奖学金（F31）授予申请旨在促进雪莉·安·爱的培训，这是一个 北卡罗来纳大学流行病学系的博士前学生。她的目标是 成为一名独立研究人员，从事创新的转化健康研究。在F31期间 培训申请人将由她的赞助商Drs指导。 Kari North和Gerardo Heiss。主题 拟议的研究是对乙醇摄入量在与年龄相关的认知中的作用的多学科评估 下降，通过遗传敏感性修饰。由于老年人数量增加 到2050年，痴呆症的痴呆症将从520万到1600万，预计医疗费用会增加 从2030亿美元到1.2万亿美元。研究乙醇摄入与认知能力下降和 痴呆症的发现不一致，可能归因于依赖于单一测量的 乙醇摄入量，非标准化认知能力下降的定义，痴呆的过时分类，简短 随访时间和或缺乏对混杂因素的分析控制和效果测量修饰符。很少的研究 尽管患病率较高，发病率和 与白人相比，黑人痴呆症的累积风险。重要的是，没有研究 乙醇摄入量对从中年到较早成年的认知的影响。此外，乙醇内的变化 代谢基因改变了乙醇氧化的速率，但很少有研究评估了效果测量。 通过祖先多样化的遗传变异来改变乙醇摄入认知的下降关系 人群。因此，基于不同种群的研究，对乙醇摄入的重复测量和 需要针对乙醇 - 代谢SNP进行基因分型的认知功能，以更好地了解 乙醇摄入量与认知能力下降的关系。这些目标将通过提议的培训来满足 该应用程序和基于双种群的基于人群的动脉粥样硬化风险的博士研究风险 摄入量45-64岁的黑白成年人的社区（ARIC）队列。 分析将包括对参加20年以上参加5项考试的参与者的重复测量 后续。这项研究回应了对身份敏感性和可修改行为因素的需求 可能会阻止或延迟认知能力下降和痴呆的进展。该研究的潜在影响是 它有能力贡献有关乙醇摄入对认知能力下降的推定影响的新信息，以及 乙醇摄入的潜在公共卫生风险和益处。