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 该博士前奖学金 (F31) 拨款申请旨在促进 Shelly-Ann Love 的培训，她是一名 北卡罗来纳大学流行病学系博士前学生。她的目标是 成为一名进行创新、转化健康研究的独立研究人员。 F31期间 申请人的培训将由她的资助者博士进行指导。卡里·诺斯和杰拉尔多·海斯。主题为 拟议的研究是对乙醇摄入在与年龄相关的认知中的作用的多学科评估 下降，由遗传易感性改变。由于老年人口数量不断增加 到 2050 年，痴呆症患者将从 520 万增加四倍，达到 1600 万，医疗费用预计也会增加 从 2030 亿美元增至 1.2 万亿美元。乙醇摄入量与认知能力下降的关系研究 痴呆症的研究结果不一致，可能归因于对单一测量的依赖 乙醇摄入量、认知能力下降的非标准化定义、过时的痴呆症分类、短期 随访时间，和/或缺乏对混杂因素和效果测量修正的分析控制。很少有研究 研究了乙醇摄入对黑人群体的影响，尽管其患病率、发病率和 与白人相比，黑人患阿尔茨海默氏症的累积风险。重要的是，没有研究调查过 乙醇摄入量对中年至老年认知的影响。此外，乙醇内的变化- 代谢基因改变乙醇氧化速率，但很少有研究评估影响措施 不同祖先的遗传变异改变了乙醇摄入量与认知能力下降的关系 人口。因此，基于不同人群的研究反复测量乙醇摄入量和 需要对乙醇代谢 SNP 进行基因分型的认知功能才能更好地理解 乙醇摄入量与认知能力下降的关系。这些目标将通过建议的培训来实现 该应用程序和博士研究基于双种族、基于人群的动脉粥样硬化风险 社区 (ARIC) 队列，由 12,773 名入学时年龄在 45-64 岁之间的黑人和白人成年人组成。 分析将包括对 20 年来参加过 5 次考试的参与者进行重复测量。 后续行动。这项研究满足了识别易感性和可改变的行为因素的需要，这些因素 可能会预防或延缓认知能力下降和痴呆的进展。该研究的潜在影响是 它能够提供关于乙醇摄入对认知能力下降的推定影响的新信息，以及 摄入乙醇的潜在公共卫生风险和益处。