Primary alcoholic dementia and alcohol-related dementia

Blackwell Publishing AsiaMelbourne, AustraliaPSYPsychogeriatrics1346-35002006 Japanese Psychogeriatric Society? 200663114118Original ArticleAlcoholic dementiay. Moriyama et al. PSYCHOGERIATRICS 2006; 6: 114 118 REVIEW ARTICLE Primary alcoholic dementia and alcohol-related dementia Yasushi MORIYAMA, 1 Masaru MIMURA, 2 Motoichiro KATO 3 and Haruo KASHIMA 3 1 Department of Psychiatry, Komagino Hospital, Tokyo, 2 Department of Neuropsychiatry, Showa University School of Medicine, Tokyo, and 3 Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan Correspondence: Yasushi Moriyama, MD, Department of Psychiatry, Komagino Hospital, 273 Uratakao, Hachioji, Tokyo, 193-8505, Japan. Email: yamori@rg7.so-net.ne.jp Received 7 November 2005; accepted 3 April 2006. Key words: alcoholic dementia, amnesia, neuropathology, neuropsychology, Wernicke Korsakoff s syndrome. Abstract Clinicopathological issues regarding so-called alcoholic dementia remain under debate. Although clinical observation favors the diagnosis of primary alcohol dementia, caused by direct alcohol neurotoxicity, further confirmation from neuropathological and biochemical perspectives is warranted. Repeat episodes of subclinical Wernicke Korsakoff s syndrome may partially account for the chronic state of primary alcoholic dementia, thus supporting the notion that primary alcoholic dementia exists in continuum with chronic and subclinical types of Wernicke Korsakoff s syndrome. Diagnostic criteria for alcohol related dementia, as detailed by Oslin et al., represent a purer form of alcoholic dementia and are useful for the scientific discussion of this condition. INTRODUCTION Oslin et al. 1 have estimated that approximately onequarter of the dementia population have alcohol related problems. The relationship between alcohol use and dementia is complicated. In the present article, we describe three clinical entities of alcoholrelated dementia: primary alcoholic dementia, due to direct alcohol neurotoxicity; Wernicke Korsakoff s syndrome, due to thiamine deficiency; and the operational diagnostic criteria for alcohol-related dementia, which is clinically different from other dementias, such as Alzheimer s disease and vascular dementia. Primary alcoholic dementia Despite recent advances in understanding the clinicopathological correlates of various dementia illnesses, including Alzheimer s disease, frontotemporal dementia and vascular dementia, the clinicopathological issues regarding so-called alcoholic dementia remain under debate. The most important, but still unresolved, question concerning alcoholic dementia is if long-term alcohol use may have direct neurotoxic effects on the brain, leading to a characteristic dementia syndrome. Primary alcoholic dementia, or the direct neurotoxicity of alcohol, may be viewed from four different perspectives: neuropathological, biochemical, neuroradiological and clinical. First, from the neuropathological viewpoint, evidence of direct alcohol neurotoxicity is poor; whether or not chronic and excessive alcohol consumption results in neocortical neuronal loss is unclear. 2 4 The difficulty of using pathological methodology to determine alcoholic toxicity partially accounts for such inconsistency. Indeed, some authors have cast doubt on the existence of primary alcoholic dementia as a neuropathological entity and suggest that the majority of cases of alcoholic dementia are in fact Wernicke Korsakoff s syndrome. 5 Second, in contrast to the paucity of neuropathological findings, there exists some biochemical evidence regarding alcohol-induced brain damage, including withdrawal-nmda receptor hyperexitability 6 and hyperhomocysteinemia. 7 However, the relationship between such biochemical abnormalities and brain dysfunction/dementia is still unclear. Third, cerebral white matter is vulnerable to chronic alcohol consumption. According to both the neuropathological viewpoint and animal models of alcoholism, alcohol-related white matter loss can be related to demyelination or to shrinkage or loss of fibers 114

Alcoholic dementia caused by cell degeneration. 8 11 In contrast to the detailed analysis available by neuropathology, anatomic magnetic resonance imaging (MRI) data, to date, has been restricted to gross estimations of white matter volumes. But recently, new developments in magnetic resonance diffusion tensor imaging (DTI) permit in vivo quantification of the microstructual deterioration of white matter tracts. 12 Using these methods, Pfefferbaum et al. 13 investigated the relationships between regional DTI measures and tests of attention and working memory in alcoholic patients, and found that white matter fiber incoherence contributes to disturbance in attention and working memory in chronic alcoholism. However, these functional effects and deficits are subtle; thus, the relationship between such abnormalities and dementia remains unclear. Fourth, clinical observation suggests the presence of cases in which dementia is due to direct alcohol toxicity, but not alcohol-related secondary causes. For example, Kato 14 described a patient with primary alcoholic dementia who underwent detailed clinical, neuropsychological and neuroimaging examinations. Following an episode of binge drinking, the patient presented with abulia, blunt affect and progressive cognitive dysfunction including severe amnesia and frontal dysfunction, which mimicked those of an advanced stage of Alzheimer s disease. The patient s score on the Mini-Mental State Examination (MMSE) was 22 and full scale IQ on the Wechsler Adult Intelligence Scale-Revised (WAIS-R) was 64. He showed no signs of nystagmus, limited eye movement or ataxia, which are frequently observed in Wernicke s encephalopathy. A 18F-fluorodeoxyglucose Positron Emission Tomography (FDG PET) finding demonstrated hypometabolism in bilateral thalamic regions and medial prefrontal cortices, without hippocampal atrophies and vascular lesions on MRI. This dementia state, however, gradually improved and almost completely resolved in 6 years. This patient was unique in that the clinical and cognitive impairments of his dementia slowly recovered, and his functional lesions included the bilateral thalami and the medial and orbital regions of the prefrontal cortex. His clinical symptoms at onset could not be explained by the typical Wernicke-Korsakoff lesions. Moreover, the patient s severe cognitive dysfunction (specifically frontal dysfunction) was reversible, while the cognitive deficits of typical Wernicke Korsakoff s syndrome are permanent. The findings in this patient suggest that from a clinical viewpoint, primary alcoholic dementia does exist, although it is rare. Wernicke Korsakoff s syndrome Wernicke s encephalopathy is an acute neurological disorder caused by thiamine (vitamin B1) deficiency. It is characterized clinically by oculomotor abnormalities, cerebellar dysfunction and an altered mental state, and pathologically by hemorrhagic lesions in the wall of the third and fourth ventricles. Korsakoff s syndrome is characterized by profound amnesia, disorientation and frequent confabulation. Because Korsakoff s syndrome often follows Wernicke s encephalopathy, and both appear to share common pathological substrates, a number of researchers describe this continuum as Wernicke Korsakoff s syndrome. 5,15 Although typical Korsakoff s syndrome presents as a pure amnesic state without significant intellectual decline, some patients are reported to show remarkable and overall dementia ( burned-out Wernicke Korsakoff s syndrome ). 5,15 Although the pathophysiology of Wernicke Korsakoff s syndrome is well understood, misdiagnosis occasionally occurs. Current criteria for diagnosing Wernicke s encephalopathy require the presence of three clinical signs (oculomotor abnormalities, cerebellar dysfunction and altered mental state), 16 although a considerable number of patients do not fulfill all the criteria. Caine et al. 17 proposed new criteria for Wernicke s encephalopathy, which require two of the following four signs: (i) dietary deficiencies; (ii) oculomotor abnormalities; (iii) cerebellar dysfunction; and (iv) either an altered mental state or memory impairment. The criteria Caine et al. 17 proposed appear to have high specificity for identifying antemortem patients with Wernicke s encephalopathy. Repeat episodes of Wernicke Korsakoff s syndrome Burned-out Wernicke Korsakoff s syndrome is difficult to differentiate from primary alcoholic dementia, as both conditions present with overall cognitive decline/dementia. However, the onset pattern provides useful information. Burned-out Wernicke Korsakoff s syndrome presents with acute onset (with nystagmus, ataxia and disturbance in consciousness) while primary alcoholic dementia presents with gradual onset 18 However, Harper 19 suggests another view, 115

Y. Moriyama et al. based on the pathological findings that Wernicke Korsakoff s syndrome may occur with gradual onset, without the apparent clinical signs of Wernicke s encephalopathy. Repeated subclinical Wernicke- Korsakoff s episodes could be an underlying cause of so-called primary alcoholic dementia. 20 Although this account of repeated subclinical Wernicke-Korsakoff s episodes, leading to alcoholic dementia, is intriguing, clinical observation hardly provides evidence for such repeat episodes of Wernicke Korsakoff s syndrome. In fact, to our knowledge, no cases of this nature had been documented until we reported one such patient, who demonstrated typical Wernicke s episodes which fulfilled clinical diagnostic criteria. 21 Following the first episode, our patient displayed amnesia and frontal lobe dysfunction, with other cognitive domains spared. This pattern of cognitive deficit remained essentially unchanged even after the second episode; neuropsychological examination of this particular patient demonstrated little change in cognitive dysfunction between the first and second episodes. However, duplicated Wernicke s episodes resulted in emotional and behavioral changes including deteriorated motivation/spontaneity together with occasional compulsive behavior (compulsive washing of clothes). Accordingly, Wernicke-Korsakoff s episodes clinically do repeat, although quite rarely. The accumulation in the literature of similar cases of overt or covert repetition of Wernicke-Korsakoff s episodes may provide clinical evidence supporting the notion of a continuum containing both Wernicke Korsakoff s syndrome and primary alcoholic dementia. Because Wernicke Korsakoff s syndrome presents with variable manifestations, caution should be paid to not overlook or miss the diagnosis. Alcohol-related dementia Although alcohol-induced persisting dementia is included in the Diagnostic and Statistic Manual of Mental Disorders, 4th edition (DSM-IV) 22 (Table 1), validity or reliability studies have not been published using these criteria. 1 The criteria for alcohol-induced persisting dementia are problematic for several reasons. First, the terms that describe abnormal alcohol use are ambiguous; for example, heavy alcohol use, problem alcohol use, or alcohol dependence. It is well known that patient reports of abuse and dependence do not necessarily correlate with the quantity and frequency of alcohol use, especially among older patients. Second, reported duration of abstinence may also be uncertain. Duration of abstinence is important in that subacute withdrawal effects can cause deterioration in cognitive functions. Clinicians often consider alcohol-related issues and dementia independently in evaluating cases of dementia. Third, the qualitative differences between alcohol-induced persisting dementia and Alzheimer s disease or vascular dementia are unclear. Based on these critical problems, and in an attempt to reduce subjective bias and standardize DSM-IV criteria, Oslin et al. 1 proposed diagnostic criteria to improve the validity and reliability of the diagnosis of alcohol related dementia (ARD). Oslin et al. 1 emphasized that ARD still remains controversial and not fully understood in terms of epidemiology and Table 1 Criteria for alcohol-induced persisting dementia in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), 4th edition, cited with modification from the American Psychiatric Association 15 A. The development of multiple cognitive deficits manifested by both: (1) Memory impairment (impaired ability to learn new information or to recall previously learned information) (2) One (or more) of the following cognitive disturbances: (a) Aphasia (language disturbance) (b) Apraxia (impaired ability to carry out motor activities despite intact motor function) (c) Agnosia (failure to recognize or identify objects despite intact sensory function) (d) Disturbance in executive functioning (i.e. planning, organizing, sequencing, abstracting) 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. C. The deficits do not occur exclusively during the course of a delirium and persist beyond the usual duration of substance intoxication or withdrawal. D. There is evidence from the history, physical examination, or laboratory findings that the deficits are etiologically related to the persisting effects of substance use (e.g. a drug of abuse, a medication) 116

Alcoholic dementia Table 2 Diagnostic criteria for alcohol related dementia, cited with modification from Oslin et al. 1 Definite alcohol related dementia At the current time there are no acceptable criteria to definitively define alcohol related dementia Probable alcohol related dementia A. The criteria for the clinical diagnosis of probable alcohol related dementia include the following: (1) A clinical diagnosis of dementia at least 60 days after the last exposure to alcohol (2) Significant alcohol use as defined by a minimum average of 35 standard drinks per week for men (28 for women) for greater than a period of 5 years. The period of significant alcohol use must occur within 3 years of the initial onset of dementia B. The diagnosis of alcohol related dementia is supported by the presence of any of the following: (1) Alcohol related hepatic, pancreatic, that is, other end organ damage. (2) Ataxia or peripheral sensory polyneuropathy (3) Beyond 60 days of abstinence, the cognitive impairment stabilizes or improves (4) After 60 days of abstinence, any neuroimaging evidence of ventricular of sulcal dilatation improves (5) Neuroimaging evidence of cerebellar atrophy, especially the vermis C. The following clinical features cast doubt on the diagnosis of alcohol related dementia: (1) The presence of language impairment (2) The presence of focal neurological signs or symptoms (3) Neuroimaging evidence for cortical or subcortical infarction, subdural hematoma (4) Elevated Hachinski Ischemia Scale Score D. Clinical features that are neither supportive nor cast doubt on the diagnosis of alcohol related dementia include: (1) Neuroimaging evidence of cortical atrophy (2) The presence of periventricular or deep white matter lesions, upon neuroimaging, in the absence of focal infarct (3) The presence of the apoprotein e4 allele One standard drink is equal to one middle size bottle of beer or two glasses of wine. pathophysiology. The authors of that study aimed to further promote studies on the etiology of putative ARD by refining its diagnostic criteria. The proposed criteria were modeled after those of the National Institute of Neurologic and Communicative Disorders and Stroke/Alzheimer s Disease and Related Disorders Association (NINCDS/ADRDA) 23 for Alzheimer s disease, providing the categories definite, probable, and possible (Table 2). Using these criteria, Oslin et al. 24 reported that individuals with ARD are less cognitively impaired and more often unmarried than patients with Alzheimer s disease, and that their cognitive and functional status both frequently stabilize. ARD is different from alcohol-induced dementia (DSM-IV) in that the presence of language impairment (aphasia) is less likely in ARD. The absence of aphasia in ARD is of clinical importance for the potential differentiation from Alzheimer s disease, frontotemporal dementia and vascular dementia. Although not all cases of Alzheimer s disease involve language impairment, the symptom of progressive deterioration of language favors the diagnosis of Alzheimer s disease. Oslin et al. s criteria 1 exclude dementia secondary to focal vascular lesions and head trauma, cases with multi risk factors and multiple brain infarctions, and those that occur after 10 years abstinence from alcohol use. Accordingly, the diagnostic criteria represent purer alcohol related dementia including Wernicke Korsakoff s syndrome, Marchiafava-Bignami disease, pellagrous encephalopathy, acquired hepatocerebral degeneration, and primary alcoholic dementia. CONCLUSION Clinicopathological issues regarding so-called alcoholic dementia remain under debate. Although clinical observation favors the diagnosis of primary alcohol dementia, as caused by direct alcohol neurotoxicity, further confirmation from neuropathological and biochemical perspectives is warranted. Repeat episodes of subclinical Wernicke Korsakoff s syndrome may partially account for the chronic state of primary alcoholic dementia, thus supporting the notion that primary alcoholic dementia exists in continuum with chronic and subclinical types of Wernicke Korsakoff s syndrome. Diagnostic criteria for alcohol related dementia, as detailed by Oslin et al., represent a purer form of alcoholic dementia and are useful for the scientific discussion of this condition. REFERENCES 1 Oslin D, Atkinson RM, Smith DM et al. Alcoholic related dementia: proposed clinical criteria. Int J Geriatr Psychiatry 1998; 13: 203 212. 117

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