CHRONIC ALCOHOL ABUSE EFFECTS ON THE AGING BRAIN

该提案的主要目标是测试两个相互对立的模型 年龄调节慢性酒精滥用对中枢神经系统功能的影响 人类的结构：与年龄相关的脆弱性模型与 累积效应模型。两人都试图解释这样一个事实，即 酒精滥用对中枢神经系统的影响在老年酗酒者中最大， 与饮酒持续时间和总饮酒量无关。如果有 承认年轻的大脑可以补偿/掩盖由 酒精，直到正常老化的线性损失使 不可能，由此得出的功能后果是累积的 年龄和酗酒的影响在老年人身上会更加明显 个人，即使该人在发病前戒酒 年纪大了。可能存在CNS变化的阈值，在该阈值中持续(或 永久性的)功能或结构变化只有在以下情况下才是明显的 已超过阈值。事实上，文献表明，永久的 中枢神经系统损害仅在(受影响最严重的)年轻人中很少见 成年或中年酗酒者。 我们将使用最先进的结构来测试这两个对立的模型 脑成像，(辅以磁化转移成像以 具体量化白质的变化)，电生理 和神经心理评估程序。这项研究将使用交叉- 横断面设计，5个研究样本，男30人，女30人： (1)50-55岁慢性(25-40岁)酗酒者戒酒15 6个月-4年，(2)65-70岁以上慢性酒精中毒患者戒酒 自55岁起，(3)65-70岁慢性酗酒者戒酒15个月- 4岁，(4)50-55岁终生轻度/不饮酒对照组，以及(5) 65-70岁终生饮酒/不饮酒对照。次要的目的是 这个项目是为了确定学生是否存在性别差异。 慢性酒精滥用对中枢神经系统功能的影响 哪种年龄会调节这些效应。 在这项研究中存在着潜在的偏见，如果一个人保持 戒酒与中枢神经系统的发病程度有关。这一要求 在酒精滥用者样本中戒酒一年可能导致 样本偏向慢性病对中枢神经系统影响较小的个体 酗酒。慢性酒精滥用的中枢神经系统发病率 与年龄有关，这种偏见在以下个人中最大 在60多岁时开始禁欲。评估这种偏见，并(作为次要的 目的)确定一年内功能和脑结构的恢复情况 关于老年人的节欲，我们将研究40个样本中的第六个 男性和40名女性65-70岁慢性酒精中毒 禁欲(即在28天的治疗计划结束时)，并将 就他们保持禁欲的情况跟踪他们15个月， 禁欲的个体在15个月的间隔结束时重新学习。

The primary goal of this proposal is to test two opposing models of how age modulates the effects of chronic alcohol abuse on CNS function and structure in humans: the age-related vulnerability model vs. the cumulative effects model. Both attempt to explain the fact that the morbid CNS effects of alcohol abuse are greatest in the elderly alcoholic, independent of duration and total amount of alcohol consumption. If one acknowledges that the younger brain can compensate/mask damage done by alcohol until the more than linear losses of normal aging make that impossible, it follows that the functional consequences of the cumulative effects of age and alcohol abuse would be much more apparent in the older individual, even if the person quit abusing alcohol before the onset of old age. There might be a threshold for CNS change, where persistent (or permanent) functional or structural change is only apparent if this threshold is surpassed. Indeed, the literature suggests that permanent CNS damage is only rarely evident in (the most severely affected) young adult or middle aged alcoholics. We will test these two opposing models using state-of-the-art structural brain imaging, (supplemented with magnetization transfer imaging to specifically quantitate changes in the white matter), electrophysiological and neuropsychological assessment procedures. The study will use a cross- sectional design with five study samples of 30 males and 30 females each: (1) 50-55 year old chronic (25-40 years of abuse) alcoholics abstinent 15 months - 4 years, (2) 65-70 year old chronic alcoholics abstinent at least since age 55, (3) 65-70 year old chronic alcoholics abstinent 15 months - 4 years, (4) 50-55 year old lifetime light/non-drinking controls, and (5) 65-70 year old lifetime light/non drinking controls. A secondary, aim of this project is to determine whether there are gender differences in the effects of chronic alcohol abuse on CNS function and in the manner in which age modulates these effects. A potential bias in this study exists if an individual's ability to remain abstinent is associated with the extent of CNS morbidity. The requirement for one year of abstinence in the alcohol abuser samples could result in samples biased toward individuals with less morbid CNS effects of chronic alcohol abuse. To the extent that CNS morbidity of chronic alcohol abuse is associated with age, this bias would be greatest in individuals who became abstinent in their 60s. To assess this bias and (as a secondary aim) to determine recovery of function and brain structure during a year of abstinence in elderly individuals, we will study a sixth sample of 40 male and 40 female 65-70 year old chronic alcoholics in very early abstinence (I-e., at the end of a 28 day treatment program) and will follow them for 15 months with regard to their maintenance of abstinence, with abstinent individuals restudied at the end of the 15 month interval.