CHRONIC ALCOHOL ABUSE EFFECTS ON THE AGING BRAIN

本提案的主要目标是测试两种对立的模型， 年龄调节慢性酒精滥用对CNS功能的影响， 结构：与年龄有关的脆弱性模型与 累积效应模型两者都试图解释一个事实， 酒精滥用对中枢神经系统的影响在老年酗酒者中最大， 与饮酒时间和饮酒总量无关。如果一个 承认年轻的大脑可以补偿/掩盖 酒精，直到超过正常老化的线性损失， 不可能的，因此，累积的功能后果 年龄和酒精滥用的影响在老年人中更为明显。 个人，即使该人在发病前停止酗酒， 老年。中枢神经系统变化可能有一个阈值，如果持续（或 功能或结构的变化只有在以下情况下才是明显的 门槛被超越了。 事实上，文献表明， 中枢神经系统损伤在（受影响最严重的）年轻人中很少明显 成年或中年酗酒者。 我们将使用最先进的结构测试这两个对立的模型， 脑成像，（补充磁化转移成像， 具体定量白色物质的变化）、电生理学的 和神经心理学评估程序该研究将使用交叉- 分区设计，5个研究样本，各30例男性和30例女性： (1)50-55岁的慢性（25-40年的滥用）酗酒者 （2）65-70岁的慢性酒精中毒者至少戒酒 自55岁起，（3）65-70岁慢性酗酒者戒酒15个月- 4年，（4）50-55岁终生轻度/不饮酒对照组，和（5） 65-70岁终生轻度/非饮酒对照。次要的，目的 该项目的目的是确定在教育方面是否存在性别差异， 慢性酒精滥用对中枢神经系统功能的影响， 哪个年龄调节这些效应。 如果一个人的保持能力 戒断与CNS发病程度相关。的要求 戒酒一年的酗酒者样本可能会导致 样本偏向于慢性炎症对CNS的病态影响较小的个体。 酗酒慢性酒精滥用的CNS发病率 与年龄有关，这种偏差在以下个体中最大： 在60多岁时开始禁欲为了评估这种偏倚，并（作为次要 目的）确定一年内功能和大脑结构的恢复情况 在老年人的禁欲，我们将研究第六个样本的40 男40例，女40例，65-70岁，慢性酒精中毒者， 禁欲（即，在28天的治疗计划结束时）， 对他们进行为期15个月的跟踪调查，以了解他们如何保持节欲， 在15个月间隔结束时重新研究禁欲个体。

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.