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: 10091376
• 负责人: Linda Kathleen McEvoy
• 金额: $ 52.16万
• 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 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10091376
• 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; Cardiometabolic Disease; Cerebral hemisphere hemorrhage; Clinical; Cognitive; Cognitive aging; Cohort Studies; Confounding Factors (Epidemiology); Data Collection; Dementia; 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; cardiovascular disorder risk; cognitive ability; cognitive function; cognitive reserve; cohort; cost; dementia risk; drinking; drinking behavior; genetic information; 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.

抽象的 随着老年人饮酒的日益普遍，有必要更好地了解酒精的使用情况。 饮酒与轻度认知障碍（MCI）风险和衰老过程中大脑健康的关系。虽然 许多研究表明，适量饮酒可以预防与年龄相关的认知障碍， 痴呆症方面，很少有研究表明适度饮酒与认知能力之间存在保护性关联 下降，或通过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 酒精与整体或区域脑容量的有害关联。调查结果有可能是 适度饮酒对认知障碍和痴呆风险的保护性关联源于 对混杂因素的控制不足，因为适度饮酒的人往往也具有较高的饮酒水平 社会经济地位并从事其他健康行为（例如定期锻炼），这些行为本身就是 与痴呆风险降低有关。相反，现有的与酒精相关的研究也有可能 使用认知衰退率或神经影像学测量方法尚未使用足够敏感的方法来 发现微妙的、积极的联系。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（R01）”旨在阐明饮酒与认知能力下降、痴呆风险的关系 通过利用一项独特的现有队列研究，研究衰老过程中大脑健康的 MCI 和神经影像指标 越南时代双胞胎老龄化研究（VETSA）。 VETSA 是一项针对约 1500 个同卵和异卵的纵向研究 男性双胞胎检查遗传和环境对衰老的影响。里面有详细的重复 酒精使用、认知功能和大脑成像测量（针对一部分参与者）的测量，以及 具有有关潜在混杂因素的大量信息。我们将确定饮酒与以下因素之间的关系： 认知能力下降率和 MCI 风险（目标 1）；并具有区域性脑灰质和白质微观结构 和白质病变负担（目标 2）。我们将确定观察到的关联是否是由于差异造成的 混杂变量，例如社会经济状况、健康状况、健康行为、认知储备或 遗传状况。对饮酒与认知/大脑结果之间的共同遗传性的检查将进一步 揭示酒精的潜在因果影响，以及对不一致双胞胎的分析。我们还将检查 酒精与认知和大脑衰老的关系是否因健康或遗传状况（包括 阿尔茨海默病或酒精代谢降低的多基因风险；目标3）。提高了以下方面的知识 酒精是否与 MCI 风险增加或降低相关，对直接公共卫生有潜在影响 影响。这项研究将为饮酒限制提供指导，以保护衰老过程中的大脑健康，并将提供 根据健康和遗传状况提出个性化的饮酒建议。