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.

摘要