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Alcohol-related dementia (alcohol-induced dementia; alcohol-related brain damage) 

Alcohol-related dementia (alcohol-induced dementia; alcohol-related brain damage)
Chapter:
Alcohol-related dementia (alcohol-induced dementia; alcohol-related brain damage)
Author(s):

Jane Marshall

DOI:
10.1093/med/9780199696758.003.0051
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date: 05 August 2020

Introduction

Long-term heavy alcohol consumption causes significant brain abnormalities and impairs cognitive functioning. A number of terms have been used to describe these effects, including: ‘alcohol-related dementia’, ‘alcohol-induced dementia’, and ‘alcoholic dementia’.(1) The more pragmatic umbrella term ‘alcohol-related brain damage’ (ARBD) is also used. The literature is beset with limitations, in particular the lack of a diagnostic gold standard, and the difficulty in making a clinical diagnosis. Many individuals labelled as having an alcohol-related dementia are, in fact, suffering from the Wernicke–Korsakoff syndrome (WKS).(2) (This is a specific neuropathological disease caused by thiamine deficiency, which can occur secondary to alcohol misuse. It is considered in Chapter 4.1.12.) When considering the topic of ‘alcohol-related dementia’ it is probably sensible to take a broad clinically-based diagnostic view that includes both WKS and other cases of ‘dementia’ that appear to be alcohol-related.(3)

Diagnostic criteria

Diagnostic criteria for ‘substance-induced persisting dementia’ are included in DSM-IV(4) (Table 4.1.11.1), which also states that there must be evidence from the history, physical examination, or laboratory findings that the deficits are aetiologically related to the persisting effects of substance use (in this case alcohol). No specific inclusion criteria are offered to distinguish alcohol-related dementia from other dementias. In ICD-10,(5) the Korsakoff syndrome is listed separately under the amnesic syndrome heading (F10.6) whereas alcohol-induced ‘dementia’ and ‘other persisting cognitive impairment’ are included under the ‘residual and late-onset psychotic disorder’ category (F10.73 and F10.74 respectively), where diagnostic guidelines can be found.

Table 4.1.11.1 DSM-IV diagnostic criteria for substance-induced persisting dementia

  1. A. The development of multiple cognitive deficits manifested by both

    1. (1) memory impairment (impaired ability to learn new information or to recall previously learned information)

    2. (2) one (or more) of the following cognitive disturbances:

      1. (a) aphasia (language disturbance)

      2. (b) apraxia (impaired ability to carry out motor activities despite intact motor function)

      3. (c) agnosia (failure to recognize or identify objects despite intact motor sensory function)

      4. (d) disturbance in executive functioning (i.e. planning, organization, sequencing, abstracting)

  1. B. The cognitive deficits in criteria A1 and A2 each cause significant impairment in social or occupational functioning and represent a significant decline from a previous level of functioning.

  1. C. The deficits do not occur exclusively during the course of a delirium and persist beyond the usual duration of substance intoxication or withdrawal

  1. D. There is evidence from the history, physical examination, or laboratory findings that the deficits are aetiologically related to the persisting effects of substance use (e.g. a drug of abuse, a medication)

Diagnostic criteria for establishing a diagnosis of ‘alcohol-related dementia’ have been proposed, conceiving it as a spectrum of alcohol-related intellectual and neurological syndromes, ranging from moderate deficits to the more severe Wernicke–Korsakoff syndrome.(3) ‘Alcohol-related dementia’ is thus defined as a syndrome that results from several aetiological mechanisms including the direct neurotoxic effects of alcohol, metabolic dysfunction during intoxication and withdrawal, trauma, vascular injury and thiamine or other nutritional deficiencies.

Prevalence

Adequate epidemiological studies to determine the size of the problem have not been carried out. It has been estimated that ‘alcohol-related dementia’ accounts for 10 per cent of the dementia population.(1) Indeed alcohol misuse may contribute to as many as 21–24 per cent of all cases of cognitive impairment in mid-adulthood.(6) The prevalence is likely to be higher in areas of socio-economic deprivation, with most cases presenting between the ages of 50 and 60 years.(7) Early onset has been associated with poorer prognosis and potential for recovery. Recent evidence suggests that the prevalence of the Wernicke–Korsakoff syndrome, caused by thiamine deficiency, may be increasing.(8,9) Early identification and intervention can help to maximize optimum recovery.

Causal mechanisms

There is no single cause of ‘alcohol-related dementia’. Individual susceptibility may be influenced by age; age of onset of drinking and the drinking history; gender; genetic background; family history of alcohol dependence; nutrition; alcohol exposure before birth; and general health status.(10) Causal mechanisms include: the neurotoxic effect of alcohol and its metabolite acetaldehyde; repeated episodes of intoxication and withdrawal; dietary neglect and vitamin deficiencies; repeated episodes of head trauma; cerebro-vascular events; and liver damage. In particular, thiamine depletion, and metabolic factors, such as hypoxia, electrolyte imbalance, and hypoglycaemia, all of which result from acute or chronic intoxication and withdrawal, are important and interrelated. It is difficult to determine the relative contributions of these mechanisms. A number of theories have been advanced by Lishman and others to explain the mechanisms by which chronic alcohol use might lead to dementia.(1,6)

  • The brain might be vulnerable to both thiamine depletion and alcohol neurotoxicity, the former affecting the basal brain regions and the latter both the basal brain and the frontal cortex.(1) Individual genetic vulnerability is likely to have a role in influencing these processes.

  • Wernicke–Korsakoff pathological processes in the basal brain have the potential to damage nearby cholinergic fibres projecting to the cerebral cortex: the so-called cholinergic hypothesis.(1,6)

  • Alcohol-induced brain pathology couples with other pro-cesses including ‘ageing, trauma, vascular changes, and hepatic dysfunc-tion’ leading to cognitive decline: the coupling hypothesis.(1,6)

  • Ethanol stimulates pituitary corticotrophin leading to elevated corticosteroid levels and possible injury to the hippocampus.

  • Recurrent alcohol withdrawal has been hypothesized to have a kindling effect.(11) During alcohol withdrawal there is increased N-methyl-d-aspartate (NMDA) function which is postulated to lead to increased neuronal excitability and to glutamate-induced neurotoxicity.(12) The way in which alcohol interferes with glutamatergic neurotransmission, especially through the NMDA receptor, is probably central to an understanding of its long-term effects on the brain.

  • Alcohol might lead to an accelerated ageing process.

Areas of the brain affected

There is evidence that the frontal lobes and sub-cortical areas such as the limbic system, the thalamus and the basal forebrain are particularly vulnerable to alcohol-related damage. The cerebellum is also vulnerable. Alcohol-related brain changes in the frontal lobes become more prominent with age.(13) Emotional processing is affected by long-standing heavy alcohol use and dependence, and probably reflects abnormalities in the limbic system and the frontal lobes.(14) This is manifested as difficulty with interpreting non-verbal emotional cues and recognizing facial expressions of emotion.

Alcohol-related brain damage has been studied using a variety of methods, ranging from the neuropathology of the post-mortem alcoholic brain to neuro-imaging techniques focusing on structural, functional and biochemical changes. There is also a considerable neuropsychological literature.

Neuropathology

Early neuropathological studies of the alcoholic brain described fairly uniform cerebral atrophy, mainly over the dorso-lateral frontal regions, widened sulci, a narrowed cortical ribbon, and enlargement particularly of the anterior horns of the lateral ventricles.(1)

The reduction in cerebral volume seen in the alcoholic brain is due mainly to the loss of white matter in the cerebral hemispheres.(15) The reduced white matter is not related to changes in hydration or changes in the chemical structure of the myelin. Selective neuronal loss in the superior frontal cortex was reported in one study(15) but not confirmed in another.(16) However, there is evidence that individual neurones are shrunken in regions where neuronal numbers are normal, such as the superior frontal, cingulate, and motor cortices.(15,16)

Animal research suggests that alcohol has a direct neurotoxic effect on the brain. Chronic ingestion of ethanol by well-nourished rats has been shown to be toxic to cholinergic projection neurones(17) and to reduce the complexity of dendritic arborization in hippocampal pyramidal neurones.(18) In the former study, transplantation of cholinergic neurones into the hippocampus and neocortex corrected the cholinergic deficits and memory abnormalities. In the latter, abstinence led to an increase in dendritic arborization.

Structural neuroimaging

Neuroimaging studies (CT and magnetic resonance imaging (MRI)) have compared recently detoxified alcoholics without obvious cognitive impairment with age-matched controls. CT studies confirmed diffuse atrophy of brain tissue, with the frontal lobes showing most extensive shrinkage.(19) Follow-up studies showed that abstinence was associated with reversibility of brain shrinkage,(19) particularly in younger individuals and in women.(20)

Structural MRI studies have reported reduced volume of both grey and white matter in the cerebral cortex, especially the frontal lobes, which are used for reasoning, judgement, and problem solving,(13) particularly in older age groups. Changes have also been shown in other structures involved in memory, such as the hippocampus (in adolescents and adults), mammillary bodies, thalamus and cerebellar cortex.(21–24) Other abnormalities include thinning of the corpus callosum and reduced volume in the pons.(25) Reduced white-matter volume is also seen in the temporal lobes (in alcohol dependent subjects with seizures) and in the cerebellar vermis where the loss is associated with deficits in postural stability.(26) More recent MRI studies have not supported the idea of increased vulnerability among women.(27) Abstinence is associated with recovery of tissue volume.

Functional neuroimaging

Functional neuroimaging studies have reported hypometabolism in the frontal and parietal cortices of chronic alcoholics without major neurological impairment, when compared with normal controls.(28–31) These abnormalities improve following abstinence,(31,32) mainly during the 16 to 30 days after the last use of alcohol. Metabolic recovery is most marked in the frontal area.(31)

Proton magnetic resonance spectroscopy can be combined with MRI, allowing in vivo insight into brain metabolism.(33–35) The metabolic changes observed in the few magnetic resonance spectroscopy studies that have been carried out suggest neuronal loss and compensatory gliosis.

Neuropsychology

Many individuals with a history of chronic excessive alcohol consumption show evidence of moderate impairment in short- and long-term memory, learning, visuoperceptual abstraction, visuospatial organization, the maintenance of cognitive set, and impulse control.(36) This tendency for alcoholics to show proportionally greater visuospatial than language-related impairments suggests that alcohol might have a selective effect on the right hemisphere: the so-called ‘right hemisphere hypothesis’.(37) However, right hemisphere functions also decline with ageing and the current view is that the functional lateralities of ‘alcoholics’ and ageing individuals are similar to normal controls.(37)

Neuropsychological performance improves with abstinence. However, impairments can be detected in apparently healthy, abstinent alcohol dependent individuals(38) and are still detectable even after 5 years of abstinence.(39) Performance on neuropsychological tests has generally been poorly correlated with structural imaging changes,(19,40) particularly with changes in grey-matter volume. However, one MRI study reported significant correlations between cortical (sulcal) and subcortical (ventricular) fluid volumes and some cognitive measures.(22) Another study, using a combination of structural (CT or MRI) and functional imaging (positron emission tomography) together with neuropsychological tests in older alcohol-dependent patients who were abstinent, found a significant correlation between degree of atrophy/metabolic functioning in the cingulate gyrus, and performance on the Wisconsin Card Sort Test.(41)

Neuropsychological test scores do not predict outcome in alcohol-dependent patients.(42,43)

Management

Difficulties in establishing a diagnosis of alcohol-related dementia/brain damage mean that it remains an ‘invisible disability’(7), usually goes unrecognized, and is often masked by other problems such as continuing alcohol consumption and withdrawal, physical ill-health, depression and associated traumatic brain damage.

All dementia work-ups should include a history of past and present alcohol use, confirmed with a collateral history.(6) Appropriate treatment of alcohol withdrawal syndromes, assessment and re-assessment should be carried out over a two-year period. Ongoing assessment and care planning are important as these patients have the capacity to improve with abstinence. The possibility of Wernicke–Korsakoff pathology in cognitively impaired patients with an alcohol use disorder should prompt swift and appropriate treatment with parenteral thiamine.(44) Oral B vitamins should be continued long-term.

The mainstay of long-term treatment in alcohol-related dementia is abstinence. This can be facilitated by a supportive non-drinking social network, and cognitive behavioural methods to teach recognition of factors that predispose to relapse and alternative coping strategies.(6) Families and care-givers facilitate success and must be actively educated and supported. A rehabilitation approach to activities of daily living and occupation is also a key factor.

Patients with alcohol-related dementia are younger and more physically active than the usual dementia population. They do not fit neatly into any category of care and are at risk of falling ‘through the net’. Services lack the capacity to manage this population so they are passed between services and find it difficult to access specialist assessment or care.

Conclusions

Alcohol-related dementia should be recognized as a preventable condition. However, identification is hampered by a lack of clarity in terminology, and a lack of standardized and specialized screening instruments and assessment procedures.(45) These individuals make repeated use of Accident and Emergency Departments, general medical, and long stay wards. Early identification would reduce their need for these services. Abstinence is the key to recovery. Treatment services should be integrated and flexible.

Further information

Baddeley, A.D., Kopelman, M/D., Wilson, B.A. (2003). The Handbook of Memory Disorders, (2nd edn.) Chichester: John Wiley and Sons Ltd.Find this resource:

Edwards, G., Marshall, E.J., Cook, C.C.H. (2003). The Treatment of Drinking Problems: a Guide for the Helping Professions, (4th edn.) Cambridge: Cambridge University PressFind this resource:

Lishman, W.A. (1998). Organic Psychiatry: The Psychological Consequences of Cerebral Disorder, (3rd edn). Oxford: Blackwell Science.Find this resource:

The National Institute of Alcohol Abuse and Alcoholism website has a portal which supports researchers and practitioners searching for information relating to alcohol research. It has a number of links to other databases: http://etoh.niaaa.nih.gov/

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