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.
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