Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California. Center for Health Sciences, SRI International, Menlo Park, California.
Alcohol Res. 2024 May 23;44(1):03. doi: 10.35946/arcr.v44.1.03. eCollection 2024.
By 2040, 21.6% of Americans will be over age 65, and the population of those older than age 85 is estimated to reach 14.4 million. Although not causative, older age is a risk factor for dementia: every 5 years beyond age 65, the risk doubles; approximately one-third of those older than age 85 are diagnosed with dementia. As current alcohol consumption among older adults is significantly higher compared to previous generations, a pressing question is whether drinking alcohol increases the risk for Alzheimer's disease or other forms of dementia.
Databases explored included PubMed, Web of Science, and ScienceDirect. To accomplish this narrative review on the effects of alcohol consumption on dementia risk, the literature covered included clinical diagnoses, epidemiology, neuropsychology, postmortem pathology, neuroimaging and other biomarkers, and translational studies. Searches conducted between January 12 and August 1, 2023, included the following terms and combinations: "aging," "alcoholism," "alcohol use disorder (AUD)," "brain," "CNS," "dementia," "Wernicke," "Korsakoff," "Alzheimer," "vascular," "frontotemporal," "Lewy body," "clinical," "diagnosis," "epidemiology," "pathology," "autopsy," "postmortem," "histology," "cognitive," "motor," "neuropsychological," "magnetic resonance," "imaging," "PET," "ligand," "degeneration," "atrophy," "translational," "rodent," "rat," "mouse," "model," "amyloid," "neurofibrillary tangles," "α-synuclein," or "presenilin." When relevant, "species" (i.e., "humans" or "other animals") was selected as an additional filter. Review articles were avoided when possible.
The two terms "alcoholism" and "aging" retrieved about 1,350 papers; adding phrases-for example, "postmortem" or "magnetic resonance"-limited the number to fewer than 100 papers. Using the traditional term, "alcoholism" with "dementia" resulted in 876 citations, but using the currently accepted term "alcohol use disorder (AUD)" with "dementia" produced only 87 papers. Similarly, whereas the terms "Alzheimer's" and "alcoholism" yielded 318 results, "Alzheimer's" and "alcohol use disorder (AUD)" returned only 40 citations. As pertinent postmortem pathology papers were published in the 1950s and recent animal models of Alzheimer's disease were created in the early 2000s, articles referenced span the years 1957 to 2024. In total, more than 5,000 articles were considered; about 400 are herein referenced.
Chronic alcohol misuse accelerates brain aging and contributes to cognitive impairments, including those in the mnemonic domain. The consensus among studies from multiple disciplines, however, is that alcohol misuse can increase the risk for dementia, but not necessarily Alzheimer's disease. Key issues to consider include the reversibility of brain damage following abstinence from chronic alcohol misuse compared to the degenerative and progressive course of Alzheimer's disease, and the characteristic presence of protein inclusions in the brains of people with Alzheimer's disease, which are absent in the brains of those with AUD.
到 2040 年，21.6%的美国人将超过 65 岁，85 岁以上人口预计将达到 1440 万。虽然并非致病因素，但年龄增长是痴呆的一个风险因素：每超过 65 岁 5 年，风险就会增加一倍；大约三分之一的 85 岁以上的人被诊断患有痴呆症。由于目前老年人的酒精摄入量明显高于前几代人，一个紧迫的问题是饮酒是否会增加患阿尔茨海默病或其他形式痴呆症的风险。
探索的数据库包括 PubMed、Web of Science 和 ScienceDirect。为了完成关于酒精消费对痴呆风险影响的叙述性综述，文献涵盖了临床诊断、流行病学、神经心理学、尸检病理学、神经影像学和其他生物标志物以及转化研究。2023 年 1 月 12 日至 8 月 1 日期间进行的搜索包括以下术语和组合：“衰老”、“酗酒”、“酒精使用障碍 (AUD)”、“大脑”、“中枢神经系统 (CNS)”、“痴呆”、“Wernicke”、“Korsakoff”、“阿尔茨海默病”、“血管”、“额颞叶”、“路易体”、“临床”、“诊断”、“流行病学”、“病理学”、“尸检”、“病理学”、“组织学”、“认知”、“运动”、“神经心理学”、“磁共振”、“成像”、“正电子发射断层扫描 (PET)”、“配体”、“变性”、“萎缩”、“转化”、“啮齿动物”、“大鼠”、“小鼠”、“模型”、“淀粉样蛋白”、“神经原纤维缠结”、“α-突触核蛋白”或“早老素”。当相关时，还选择了“物种”（即“人类”或“其他动物”）作为附加过滤器。尽量避免查阅综述文章。
术语“酗酒”和“衰老”检索到约 1350 篇论文；添加短语，例如“尸检”或“磁共振”，将数量限制在不到 100 篇论文。使用传统术语“酗酒”和“痴呆症”得到了 876 条引用，但使用目前公认的术语“酒精使用障碍 (AUD)”和“痴呆症”仅产生了 87 篇论文。同样，术语“阿尔茨海默病”和“酗酒”产生了 318 个结果，而“阿尔茨海默病”和“酒精使用障碍 (AUD)”仅返回了 40 个引用。由于相关的尸检病理学论文发表于 20 世纪 50 年代，而最近的阿尔茨海默病动物模型是在 21 世纪初创建的，因此引用的文章跨越了 1957 年至 2024 年。总共考虑了 5000 多篇文章，其中约有 400 篇被引用。
慢性酒精滥用会加速大脑衰老并导致认知障碍，包括记忆障碍。然而，来自多个学科的研究共识是，酒精滥用会增加痴呆症的风险，但不一定是阿尔茨海默病。需要考虑的关键问题包括与阿尔茨海默病的退行性和进行性病程相比，慢性酒精滥用停止后大脑损伤的可逆性，以及阿尔茨海默病患者大脑中特征性存在的蛋白包涵体，而这些蛋白在 AUD 患者的大脑中不存在。
