The relative roles of alcohol per se,
thiamine deficiency, and
liver disease in the pathogenesis of alcohol-related brain damage have not been fully elucidated. In particular, the extent to which alterations of brain
thiamine metabolism contribute to
cognitive dysfunction in
alcoholism in the absence of
Wernicke's encephalopathy has not been established. In the present study,
thiamine diphosphate-dependent
enzymes were measured using standard spectrophotometric techniques in homogenates of brain tissue obtained at autopsy from eight alcoholic patients, all of whom died in
hepatic coma without clinical or neuropathological evidence of
Wernicke's encephalopathy and six nonalcoholic, age-matched controls, matched for autopsy delay time and free, at the time of death, from gross
malnutrition or other neurological or
psychiatric disorders.
Transketolase activities were reduced in cerebellum (by 35%, p < 0.01), thalamus (by 35%, p < 0.01), frontal cortex (by 22%, p < 0.01), temporal cortex (by 20%, p < 0.01), and prefrontal cortex (by 19%, p < 0.01). Activities of the
pyruvate dehydrogenase complex were selectively reduced in prefrontal cortex by 25% (p < 0.01). Activities of
alpha-ketoglutarate dehydrogenase were within normal limits in all brain regions of alcoholic patients. The generalized reductions of
transketolase activity undoubtedly result from
thiamine deficiency. Previous studies suggest that the presence of
liver disease may exacerbate
thiamine deficiency in alcoholics. A sustained loss of
transketolase activity in brain could result in disruption of pentose shunt activity and concomitant reductions in reducing equivalents and lipid metabolism within the cell. The selective loss of
pyruvate dehydrogenase activity in prefrontal cortex of alcoholic cirrhotics could relate to the phenomenon of
hepatic coma.(ABSTRACT TRUNCATED AT 250 WORDS)