Effects of alcoholism on brain size.

The definition of alcoholism has long been marked by uncertainty and conflict, yet no better term exists to describe chronic and dependent overconsumption. Alcohol is drunk mostly for its pharmacological effects on the central nervous system (CNS), and when dependence sets in, consumption is increased because of tolerance and the need to avoid withdrawal symptoms. The effects on the CNS include direct intoxication, the consequences of withdrawal after tolerance, cerebral trauma related to intoxication, cerebro-vascular events, and the results of liver disease and secondary malnutrition. The question of diffuse cerebral atrophy in alcoholics with attendant functional deficits has had a chequered history.' Courville2 found widespread cortical atrophy in alcoholics at autopsy, and believed that alcoholism was the commonest cause of these changes in the 5th and 6th decades of life. Subsequent neuropathological studies have been discordant on the issue, perhaps not surprisingly when one considers the difficulties inherent in charting loss of components in so complex and crowded an area as the cortex, without specific markers. Air-encephalographic indications of atrophy3 were subject to the charge that patients were specially selected for the procedure. Fresh impetus has come from computed tomographic (CT) scan studies, which uniformly reveal a high incidence of cortical shrinkage and ventricular dilatation in large and relatively unselected populations of alcoholics.4'5 Psychometry has revealed, even after thorough 'drying out', widespread cognitive deficits affecting memory, psychomotor speed, visuospatial and abstracting abilities and complex reasoning.6 CT evidence suggests that about half to two thirds of alcoholics develop atrophy, often from quite early on in their alcoholic careers.5 A proportion of severe alcoholics escape entirely for reasons which remain unclear but include genetic factors, age and sex. Genetic factors are indicated by more severe CT scan changes in familial than non-familial alcoholics.7 Age has repeatedly been shown to correlate with most indices ofCT change, but it is difficult to separate the effects ofage from those ofthe duration ofalcoholism. The equivalence of CT abnormalities in older alcoholics with short and long drinking histories suggests that with advancing age the brain becomes more vulnerable to de novo exposure to alcohol.5'8 The rate of cerebral atrophy with aging eventually plateaus out in male alcoholics as indicated by CT scan9 and autopsy studies.'" Female alcoholics may be at greater risk, as they reveal equivalent ventricular enlargement and widening of the cortical fissures, but not sulci, after a shorter drinking history and at a lower peak alcohol consumption than male alcoholics.9 This accords with the female susceptibility to psychological deficits'" and to alcoholic liver disease.",2 The abnormal changes resolve slowly with prolonged abstinence.5'3 The rate of recovery of brain shrinkage is too gradual for it to be explained by restoration to normal of water and electrolyte changes. Regeneration of dendritic spines'4 occurs and changes in glial and neuronal proteins'5 persist with abstinence. Does prolonged abstinence ultimately lead to total restitution of normal brain morphology? Cross-sectional studies comparing alcoholics with Alcoholics Anonymous (AA) members, who report prolonged abstention after equally severe drinking histories, reveal some degree of persistent ventricular dilatation in AA males, though with more complete restitution in AA females.9 The cortical sulci appear to have recovered completely in both sexes. X-ray absorption densities of frontal white matter are elevated in abstinent alcoholics compared to controls.'6 This could be related to the altered lipid content of white matter reported by Lesch et al.'7 Recent autopsy studies are beginning to confirm the validity of the CT scan findings. Brain weights were found to be significantly reduced in large numbers of male alcoholics compared to controls with a mean difference of 31 ' or 71 grams."' A quantitative estimate of the pericerebral space has been developed by Harper et al."' from measures of the intracranial