Neurocognition and Performance after Moderate Drinking in Older Adults

描述(由申请人提供)：人们越来越多地关注适度饮酒的潜在好处，特别是在中老年人中。重要的是，这些工作大多侧重于将适量饮酒作为一种生活方式，而没有直接考虑适量饮酒对老年饮酒者的急性影响(即，将适量饮酒作为一种事件)。关于中等剂量的急性酒精对成年中后期健康成年人的神经认知、神经生理学和表现指标的影响，人们知之甚少。从科学的角度来看，这些数据的缺乏限制了关于酒精对行为的直接影响以及可能影响结果的代偿神经行为机制的结论。从临床的角度来看，缺乏数据极大地限制了对越来越多的人群中与适度饮酒相关的短期风险的建议。试点研究(部分支持，NIAAA R03AA14039，尼克松，首席研究员)揭示了年龄效应，表明低剂量的酒精对上升肢的负面影响比对下降肢的负面影响更大，但仅适用于年龄较大(相对于较年轻的)参与者/受试者(SS)。有趣的是，年龄较大的那组人也较少意识到自己的赤字。重要的是，年龄相关的药代动力学差异不能解释这些结果[40]。有趣的是，在呼吸酒精浓度峰值时评估的视觉注意力(~0.04%)对于接受酒精的老年SS和那些实际接受安慰剂但认为他们已经接受了酒精的人同样受到损害[39][参见第3节]。不幸的是，所有条件的代表性不足以进行与性别有关的分析。这些数据提供了概念性指导，并加强了系统研究的可行性和必要性，其中包括更大的剂量范围、更大的性别分析样本和更全面的神经行为评估。因此，我们建议一项双盲安慰剂对照研究，使用2(年龄：年轻(25-35)/年长(55-70))×2(性别)×3(安慰剂，低(~0.04%)和中等(~.065%))酒精剂量析因设计，以阐明这些变量对精神运动速度、定格转移能力、注意力过程和复杂综合行为(即驾驶模拟)的主要和交互影响。为了增强这项工作的理论重要性，我们引入了当前的认知衰老模型。这项研究对中度(即合法)急性酒精水平、健康衰老和认知以及对酒精管理的神经行为影响敏感度的性别差异的基础和应用研究具有重要意义。 公共卫生相关性：人们越来越关注适度饮酒生活方式对心血管和生活质量的潜在益处，特别是在中年人和老年人中。然而，很少有系统的工作集中于这些中等剂量对认知和表现变量的急性影响，这些变量对有效的高阶功能至关重要，包括决策和跟踪信息。在我们试点工作的基础上，该项目比较了男性和女性、年龄较大和年龄较小的中度饮酒者在三种酒精条件下的表现，这些酒精条件旨在实现血液酒精浓度为零(安慰剂(0)、低水平(~0.04%)或中等水平(~0.065%))，以检查1)老年人在多大程度上以及在何种低到中等剂量的酒精下可能表现出不同的敏感性，以及2)老年饮酒者是否能够准确地预测到与酒精相关的缺陷。这些发现不仅可以让我们将年龄与酒精对神经认知任务的影响分开，还可以揭示在没有问题的老年饮酒者中，与适度饮酒相关的不同伤害风险和负面后果。

DESCRIPTION (provided by applicant): There has been increasing attention directed to the potential benefits of moderate drinking, particularly in middle-aged to older adults. Importantly, most of this work has focused on moderate drinking as a lifestyle, without direct consideration of the acute effects of moderate doses of alcohol on older drinkers (i.e., moderate drinking as an event). Little is known about the effects of moderate doses of acute alcohol on neurocognitive, neurophysiological and performance measures among healthy adults in middle to later adulthood. From a scientific perspective, the absence of these data restrains conclusions regarding the direct effects of alcohol on behavior as well as the compensatory neurobehavioral mechanisms that may impact outcome. From a clinical perspective, the absence of data greatly restrains recommendations regarding the short-term risks associated with bouts of moderate drinking for a growing segment of the population. Pilot work (partial support, NIAAA R03AA14039, Nixon, principal investigator) revealed age effects suggesting that a low dose of alcohol negatively affected performance on the ascending limb to a greater extent than on the descending limb, but only for older (as opposed to younger) participants/subjects (Ss). Interestingly, the older group was also less aware of their deficits. Importantly, age-related differences in pharmacokinetics could not account for these results [40]. Interestingly, visual attention assessed at peak breath alcohol concentration (~.04 percent) was impaired equally for older Ss who received alcohol and those who actually received placebo but believed they had received alcohol [39] [See Section 3]. Unfortunately, representation across the conditions was not sufficient to allow gender- related analyses. These data provide conceptual guidance and reinforce the feasibility of and need for a systematic study that includes a greater dose range, larger samples for gender analyses, and more comprehensive neurobehavioral assessments. Therefore, we propose a double-blind placebo controlled study using a 2 (age: younger (25-35)/older (55-70)) by 2 (gender) by 3 (placebo, low (~.04 percent), and moderate (~. 065 percent)) alcohol dose factorial design to clarify the main and interactive effects of these variables on psychomotor speed, set-shifting abilities, attentional processes, and complex integrated behavior (i.e., driving simulation). To enhance the theoretical import of the work, we bring current models of cognitive aging to bear. The study has significant relevance to basic and applied studies of moderate (i.e., legal) levels of acute alcohol, healthy aging and cognition, and gender differences in sensitivity to the neurobehavioral effects of alcohol administration. PUBLIC HEALTH RELEVANCE: There has been increasing attention to potential cardiovascular and quality of life benefits associated with a moderate drinking lifestyle, particularly in middle aged to older adults. However, little systematic work has focused on the acute effects of these moderate doses on cognitive and performance variables critical to effective higher order functions including decision-making and tracking information. Building on our pilot work, this project compares performance between male and female older and younger moderate drinkers under 3 alcohol conditions designed to achieve zero blood alcohol concentration (placebo (0), a low level (~.04 percent) or a moderate level (~ .065 percent) to examine 1) to what extent and under what low-to-moderate alcohol doses older adults may demonstrate differential sensitivity and 2) whether older drinkers can accurately anticipate alcohol- related deficits. The findings will not only allow us to disentangle age from alcohol effects on neurocognitive tasks, but also shed light on differential risk for injury and negative outcome associated with episodes of moderate drinking among non-problem, older drinkers.