Alcohol and Neurodegeneration Fulton T. Crews Center for Alcohol Studies, University of North Carolina, Chapel Hill, North Carolina, USA Key words: Alcohol—Alcoholism—Apoptosis—Brain damage—Excitotoxicity—Neuroto- xicity—Oxidative stress. NEUROTOXICITY OF ALCOHOL Studies of alcohol-induced brain damage have clearly indicated that alcohol is neurotoxic. Alcoholics are at increased risk for brain damage from a variety of causes, in- cluding poor nutrition, liver disease, and head trauma. Further, alcoholic dementia is the second leading cause of adult dementia in the United States, accounting for approximately 10% of the cases (Alzheimer’s disease is the leading cause, accounting for 40 to 60% of cases). A variety of studies report that 50 to 75% of sober, detoxified, long-term al- cohol-dependent individuals suffer from some degree of detectable cognitive impairment with approximately 10% suffering from serious dementia. Although more research is re- quired to precisely delineate the effects of alcohol on various types of brain function, there appears to be a continuum of moderate deficits in the majority of long-term alcoholics, progressing to much more severe deficits of Wernicke’s disease and Wernicke’s ence- phalopathy with Korsakoff’s amnestic syndrome (12,79). A variety of lifestyle factors, in- cluding nutrition, are implicated in the more severe cases. However, all of these on the continuum appear to be related to alcohol consumption and to the amount of alcohol con- sumed. That is, the more severe cases are associated with more severe and chronic long- term alcoholism (12,79). Alcohol-induced changes in the structure of the adult brain have been studied in both humans and rodents. A variety of postmortem histological analyses, as well as supporting imaging analysis, suggest that chronic alcohol changes brain structure. Computed tomog- raphy (CT) and magnetic resonance imaging (MRI) studies of human brain have re- peatedly shown enlargement of the cerebral ventricles and sulci in most alcoholics. The enlargement of the ventricles and sulci essentially reflects a shrinking of the brain mass. This is consistent with studies on postmortem brain tissue, where alcoholics have a re- duction in total brain weight. Particularly severe alcoholics have reductions in the global cerebral hemisphere and cerebellar brain weights that are significantly reduced compared 379 CNS Drug Reviews Vol. 5, No. 4, pp. 379–394 © 1999 Neva Press, Branford, Connecticut Address correspondence and reprint requests to Dr. F. T. Crews, Center for Alcohol Studies, University of North Carolina at Chapel Hill, CB#7178, Thurston Bowles Building, Chapel Hill, NC 27599 – 7178. Fax: +1 (919) 966-5679; E-mail: ftcrews@med.unc.edu.