Ethanol and brain damage
Introduction
Alcohol dependence (described hereafter as ‘alcoholic’) and abuse is one of the most costly health problems in the world from both a social and an economic point of view. Patterns of drinking appear to be changing throughout the world, with more women and young people drinking heavily 1., 2.••. In the US, alcohol dependence and abuse is estimated to cost $184.6 billion annually [3]. Drinking alcohol at high risk levels for long-term harm was estimated to account for approximately 4% of all male deaths and 2% of female deaths in 1997, with approximately 50 000 hospitalisations [4]. Similar alcohol-related problems are seen in most other countries in the world. Excessive drinking can lead to impairment of cognitive function and structural brain changes — some permanent, some reversible. Patterns of damage appear to relate to lifetime alcohol consumption but also equally importantly to associated medical complications. The most important of these is Wernicke-Korsakoff syndrome — a nutritional vitamin deficiency state that is caused by thiamin deficiency but which is seen most commonly in alcoholics. This disorder is preventable through supplementation of the diet by thiamin [5] and an awareness by health professionals to treat ‘at risk’ patients with thiamin.
Section snippets
Neurological deficits
Impairments of neurological function commonly seen in alcohol dependency include deficits in abstract problem solving, visuo-spatial and verbal learning, memory function, perceptual motor skills and even motor function [6]. Using transcranial magnetic stimulation, Ravaglia et al. [7] showed that chronic alcoholics had a significant prolongation of central motor conduction time compared with controls, but that there was no correlation between intensity and duration of abuse. The pattern of
Co-morbidity
Sullivan et al. [10•] have shown that patients with co-morbid schizophrenia and alcohol dependence are at risk for alcohol-related reductions in the volume of pontine structures that are not affected by schizophrenia per se. Repeated experience of withdrawal from alcohol (most alcoholic patients have multiple episodes of binge drinking followed by abstinence) is also associated with impaired cognitive function, although it appears that this only applies to specific cognitive tasks [11]. Other
Structural changes in the brain
Neuroimaging techniques have demonstrated structural and functional abnormalities in uncomplicated alcoholics (those who have no liver disease or Wernicke-Korsakoff syndrome) who are cognitively impaired [13]. However, the question of whether ‘moderate’ alcohol consumption is associated with such dangers is more difficult to answer. Ding et al. [14] used data from the Atherosclerotic Risk in Communities study (ARIC) and showed that alcohol consumption was proportional to the size of the
Alcohol-related brain damage — mechanisms
There are several mechanisms that have been proposed to explain ethanol-related brain damage — these are not mutually exclusive.
It is well known that ethanol, when administered acutely in a pharmacologically relevant dose, selectively and potently inhibits the function of N-methyl-d-aspartate (NMDA) receptors. The precise site of action has not yet been demonstrated. Chronic exposure to ethanol causes adaptive upregulation in sensitivity of NMDA receptors both in vivo and in vitro, which can
Prevention of alcohol-related brain damage
Alcohol-related Wernicke-Korsakoff syndrome is still a worldwide problem. Case reports are seen regularly in a range of medical journals from almost every country in the world. Although many of these cases have a history of alcohol abuse, other cases are related to poor nutrition, long-term parenteral feeding, gastrectomy, diets, AIDS, hyperemisis gravidarum and other conditions 46., 47., 48., 49., 50., 51.. Specific recommendations have been made by the Royal College of Physicians (London) for
Conclusions
Although various hypotheses have been proposed to explain the mechanisms underlying alcohol-related brain damage and consequent cognitive dysfunction, only a few studies have been conducted on human brain tissue. Both hypothesis- and non-hypothesis-driven approaches should significantly contribute to our understanding of this complicated pathology. Understanding the functional nature of disease has potential to lead to the development of new treatment and/or intervening strategies.
References and recommended reading
Papers of particular interest, published within the annual period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Acknowledgements
This research was supported by the National Institute of Alcoholism and Alcohol Abuse (NIAAA – 2RO1 AA012725-04), the University of Sydney, the Neuroscience Institute of Schizophrenia and Allied Disorders, the Australian Brewers’ Foundation and the NSW Department of Health.
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