Moderate alcohol use: risk or protective factor for age-related cognitive decline, mild cognitive impairment, and brain health in aging

适量饮酒：与年龄相关的认知能力下降、轻度认知障碍和衰老过程中大脑健康的风险或保护因素

• 批准号: 9904468
• 负责人: Linda Kathleen McEvoy
• 金额: $ 51.74万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-15 至 2022-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9904468
• 关键词: Address; Adverse effects; Affect; Age; Age-associated memory impairment; Aging; Alcohol consumption; Alcoholic beverage heavy drinker; Alcohols; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Anti-Inflammatory Agents; Antioxidants; Behavior; Behavioral; Brain; Brain imaging; Cerebral hemisphere hemorrhage; Clinical; Cognitive; Cognitive aging; Cohort Studies; Confounding Factors (Epidemiology); Data Collection; Dementia; Disease; Dose; Elderly; Enzymes; Ethanol Metabolism; Exercise; Genetic; Genetic Predisposition to Disease; Genetic Risk; Genetic Status; Genotype; Goals; Guidelines; Health; Health Status; Health behavior; Heritability; Hippocampus (Brain); Impaired cognition; Impaired health; Individual; Individual Differences; Inflammation; Intake; Investments; Knowledge; Lesion; Light; Longitudinal Studies; Measures; Mediating; Methods; Microscopic; Military Personnel; Modification; Neuropsychology; Outcome; Oxidants; Participant; Population; Predisposition; Prevalence; Proxy; Public Health; Recommendation; Research Design; Resources; Risk; Risk Factors; Sampling; Societies; Socioeconomic Status; Structure; Suggestion; Twin Multiple Birth; Twin Studies; United States National Institutes of Health; Vietnam; Woman; aging brain; alcohol effect; alcohol exposure; alcohol risk; amyloid pathology; base; brain health; brain volume; cardiometabolism; cardiovascular disorder risk; cognitive ability; cognitive function; cognitive reserve; cohort; cost; dementia risk; drinking; drinking behavior; genetic information; genetic profiling; genome-wide; good diet; gray matter; high risk; higher education; hippocampal atrophy; improved; indexing; male; men; middle age; mild cognitive impairment; modifiable behavior; neuroimaging; neurotoxic; personalized medicine; preservation; protective factors; psychosocial; stem; white matter

ABSTRACT With the increasing prevalence of alcohol use among older adults, it is imperative to better understand the association of alcohol use with risk of mild cognitive impairment (MCI) and brain health in aging. Although many studies suggest that moderate drinking may protect against age-related cognitive impairment and dementia, few studies have demonstrated a protective association of moderate drinking with rates of cognitive decline, or with neuroimaging measures of preserved brain health. Most neuroimaging studies have shown detrimental associations of alcohol with global or regional brain volumes. It is possible that findings of protective associations of moderate drinking on risk of cognitive impairment and dementia stem from inadequate control for confounders since individuals who drink moderately also tend to be of higher socioeconomic status and to engage in other healthy behaviors (such as regular exercise), that are themselves associated with reduced risk of dementia. Conversely, it is also possible that existing studies relating alcohol use to rates of cognitive decline or neuroimaging measures have not used sufficiently sensitive methods to detect subtle, positive associations. Individual differences in genetic predisposition to Alzheimer's disease, or in alcohol metabolizing enzymes, may also obscure effects. The goal of this project, which is responsive to PAR-17-054 “Leveraging Existing Cohort Studies to Clarify Risk and Protective Factors for Alzheimer's Disease and Related Dementias (R01)” is to clarify the association of alcohol use with cognitive decline, risk of MCI and neuroimaging metrics of brain health in aging by leveraging a unique existing cohort study, the Vietnam Era Twin Study of Aging (VETSA). VETSA is a longitudinal study of ~1500 monozygotic and dizygotic male twin pairs that examines genetic and environmental influences on aging. It contains detailed repeated measures of alcohol use, cognitive function, and brain imaging measures (on a subset of participants), along with a wealth of information on potential confounders. We will determine how alcohol use is associated with rates of cognitive decline and risk of MCI (Aim 1); and with regional brain grey and white matter microstructure and white matter lesion burden (Aim 2). We will determine if observed associations are due to differences in confounding variables, such as socioeconomic status, health status, health behaviors, cognitive reserve or genetic status. Examination of shared heritability between drinking and cognitive/brain outcomes will further inform on potential causal effects of alcohol, as will analyses of discordant twin-pairs. We will also examine whether associations of alcohol with cognitive and brain aging differ by health or genetic status (including polygenic risk for Alzheimer's disease, or for reduced alcohol metabolism; Aim 3). Improved knowledge of whether alcohol is associated with increased or decreased risk of MCI has potential for direct public health impact. This study will inform guidelines for alcohol limits to preserve brain health in aging and will provide for individualized recommendations on alcohol use based upon health and genetic status.

摘要 随着老年人饮酒的日益普遍，必须更好地了解 酒精使用与轻度认知障碍（MCI）风险和老年大脑健康的关系。虽然 许多研究表明，适量饮酒可以防止与年龄有关的认知障碍， 尽管有研究表明，适度饮酒与认知功能障碍的发生率存在保护性关系， 下降，或与神经影像学措施保持大脑健康。大多数神经影像学研究表明 酒精与全球或区域脑容量的有害关联。有可能， 适度饮酒与认知障碍和痴呆症风险的保护性联系源于 对混杂因素的控制不足，因为适度饮酒的个体也倾向于更高的 社会经济地位和从事其他健康的行为（如定期锻炼），这是他们自己 与降低痴呆症风险有关。相反，现有的关于酒精的研究也可能 使用认知能力下降率或神经影像学测量没有使用足够敏感的方法， 发现微妙的积极联系阿尔茨海默病遗传易感性的个体差异，或 在酒精代谢酶中，也可能掩盖其影响。该项目的目标是响应 PAR-17-054“利用现有队列研究阐明阿尔茨海默病的风险和保护因素 疾病和相关痴呆症（R 01）”是为了澄清酒精使用与认知能力下降， MCI和神经影像学指标的大脑健康的老龄化，利用一个独特的现有队列研究， 越南时代老龄化双胞胎研究（VETSA）。VETSA是对约1500个单合子和双合子的纵向研究。 研究基因和环境对衰老影响的男性双胞胎。它包含了详细的重复 酒精使用、认知功能和脑成像测量（对一部分参与者）的测量，沿着 有大量关于潜在混杂因素的信息我们将确定酒精的使用是如何与 认知下降率和MCI风险（目标1）;以及局部脑灰质和白色物质微结构 和白色病变负荷（Aim 2）。我们将确定观察到的关联是否是由于以下方面的差异造成的： 混杂变量，如社会经济状况、健康状况、健康行为、认知储备或 基因状态对饮酒和认知/大脑结果之间的共同遗传性的研究将进一步 告知酒精的潜在因果影响，以及对不和谐双胞胎的分析。我们亦会研究 酒精与认知和大脑衰老的关系是否因健康或遗传状态（包括 阿尔茨海默病或酒精代谢降低的多基因风险;目的3）。进一步了解 酒精是否与MCI风险的增加或降低相关， 冲击这项研究将为酒精限制提供指导方针，以在衰老过程中保持大脑健康，并将提供 根据健康和遗传状况提供个性化的酒精使用建议。