Mohammed T. Abou-Saleh

Principles and Practice of Geriatric Psychiatry.Editors: Professor John R. M. Copeland, Dr Mohammed T. Abou-Saleh and Professor Dan G. BlazerCopyright & 2002 John Wiley & Sons LtdPrint ISBN 0-471-98197-4 Online ISBN 0-470-84641-052Alcoholic and Other Toxic DementiasE. M. JoyceImperial College School of Medicine, London, UKALCOHOLIC DEMENTIAThe concept of a dementia consequent upon the effects of longtermalcohol abuse developed from clinical observations of agradual deterioration in personality and intellect in manyalcoholics. Recent studies suggest that this is age-related, ismilder in degree than the neurodegenerative dementias and can bepresent in 11–24% of demented patients 1–3 . Alcoholic dementiawas originally considered to be distinct from the amnesia of theWernicke–Korsakoff syndrome, which also occurs in alcoholicsbut is caused by thiamine malnutrition rather than alcoholneurotoxicity. Horvath 4 prospectively examined 100 chronicalcoholics presenting with a dementia syndrome and concludedthat ‘‘alcoholic dementia’’ is not synonymous with the Wernicke–Korsakoff syndrome, and that other non-amnesic organicsyndromes exist in alcoholics, characteristic of frontal, parietalor global cortical damage. Cutting 5 performed a retrospectivecase-note analysis of alcoholic patients with cognitive impairmentand found two forms of clinical presentation. One consisted of arapidly developing illness in younger patients with preservedintellect, akin to the traditional Wernicke–Korsakoff syndrome,whereas the other was more characteristic of dementia, being agradual and global cognitive deterioration in older patients.This concept was soon challenged by the results of clinicopathologicalstudies. Torvick et al. 6 examined the clinical records ofpatients who, at autopsy, had diencephalic lesions characteristic ofthiamine malnutrition. Of these, 75% were considered to bedemented in life rather than amnesic and the majority had noadditional neuropathological hallmarks of a neurodegenerativedementia. Torvick et al. concluded that the diencephalic lesions ofthiamine deficiency can result in the clinical pictures of both‘‘alcoholic dementia’’ and the Wernicke–Korsakoff syndrome.Victor and Adams 7 then pointed out that 10% of their pathologically-provencases of the Wernicke–Korsakoff syndrome developedcognitive abnormalities insidiously, rather than acutely 8 ,andthatcognitive impairments other than amnesia, and behaviouralabnormalities such as inertia and apathy, can be demonstrated inthese patients 9 . Thus, they argued that, depending on the severity ofthe non-mnemonic deficits or the mode of presentation, cases of theWernicke–Korsakoff syndrome may be misattributed as cases ofalcoholic dementia. The neuropathological studies of Harper andcolleagues 10,11,62 are in agreement with this. They found that twothirdsof the alcoholics coming to post mortem in their unit hadlesions of thiamine deficiency, yet only one-third of these hadreceived a clinical diagnosis of Wernicke–Korsakoff syndrome inlife. In the remainder, the most common diagnosis was dementia.Thus far, the evidence points to the conclusion that subcorticallesions caused by thiamine malnutrition can be sufficient toexplain both amnesia and dementia witnessed in alcoholics.However, Victor and Adams 7 and Torvick et al. 6 did not assumethat all cases of alcoholic dementia are unrecognized cases of theWernicke–Korsakoff syndrome. Both considered that superaddedcerebral lesions may explain the dementia-like presentation of aproportion of patients with the Wernicke–Korsakoff syndrome.Because these additional lesions can be attributed to a variety ofpathological processes, including chronic hepatocerebral degeneration,communicating hydrocephalus, Alzheimer’s disease andischaemic infarction, they argued that there is no need to invoke aspecial process of alcohol neurotoxicity. More recent researchsupports this contention. Kasahara et al. 2 compared young (35–45years) and old (460 years) alcoholics and found evidence ofdementia only in the older group. Most cases had additionalmedical diagnoses, including hypertension, liver disease andcardiomyopathy, and no case of dementia could be accountedfor by the direct effect of alcohol.Although dementia in alcoholics is unlikely to be caused solelyby alcohol neurotoxicity, there is compelling evidence to suggestthat alcohol is neurotoxic. Carefully controlled neuropathologicalstudies have frequently found whole brain atrophy, predominantlyinvolving the white matter, in chronic alcoholics 12–16 . Neuronaldeath has been found in specific areas of the frontal associationcortex 17–19 and neuronal shrinkage in the cingulate and motorcortex 17,20,21 . The contribution of liver failure to this neuropathologyhas been assessed in several studies and the bulk of evidencesuggests that cirrhosis alone does not account for the brainshrinkage witnessed in alcoholics 13,15,22 . However, existing studiesof the contribution of thiamine malnutrition to such findings areequivocal with evidence that thiamine deficiency both does anddoes not cause the cortical damage seen in alcoholics 13,15 . Medialtemporal lobe limbic structures, i.e. the hippocampus and theamygdala, have been foci of interest because of their involvementin cognitive function. Reduced volumes have been reported inalcoholics but, again, it is not clear whether it is alcohol per se orthiamine deficiency that accounts for this 16,19,23–25 .It can be concluded from these studies that: (a) alcohol itselfcan cause neuronal damage; (b) liver disease per se is not a majorfactor in the aetiology of the neuropathological changes; and (c)thiamine malnutrition potentiates the neurotoxic effect of alcoholon the brain. Butterworth 26 proposes mechanisms to explain theseconclusions. He argues that thiamine deficiency is common inalcoholism because of poor diet and gastrointestinal disorder.Alcohol and its metabolite acetylaldehyde are directly neurotoxicand have toxic effects on thiamine-dependent enzymes in brainand liver. In turn, liver disease disrupts thiamine homeostasis andcauses astrocytic damage. The latter results in the loss of neuron–astrocyte trafficking of neuroactive amino acids and thiaminePrinciples and Practice of Geriatric Psychiatry, 2nd edn. Edited by J. R. M. Copeland, M. T. Abou-Saleh and D. G. Blazer&2002 John Wiley & Sons, Ltd