Alcoholic Korsakoff Research Articles

Amnesic Pathologies in Regulation of Dopamine as Supplement to Wernicke-Korsakoff Syndrome: A Limbic-Reticular Coupling View

Background: It was suggested by the limbic-reticular coupling theory that the hippocampus and amygdala regulate such descending limbic structures as the mammillary bodies, septum, hypothalamus and habenula, and in turn regulate the ascending noradrenergic, serotonergic, dopaminergic and cholinergic systems to consolidate and recall declarative memory, while the anterior and mediodorsal thalamic nuclei of Wernicke-Korsakoff syndrome beyond limbic-reticular coupling be related else to familiarity. Aim: It was aimed to highlight a portion of limbic-reticular coupling structures in alcoholic Korsakoff’s syndrome, including the dopaminergic system, habenula, mammillary bodies, etc. Methods: It was searched the papers from Pubmed and Baidu. Results and Discussions: It is highlighted that, (a) the mesolimbic dopamine, liable to be affected by alcohol, induces the hippocampal theta rhythm via septum, helping encode and consolidate new memories, such as dopaminergic enhancement of motivational declarative memory in young human adults; (b) dopamine can activate cortical gamma wave and help recall; (c) joint damage of habenula and mammillary bodies, both sending efferents to ventral tegmental area(VTA) rich in dopaminergic neurons, is sufficient to cause Korsakoff’s amnesia; (d) the loop of hippocampal CA3 to lateral septum(LS) to VTA(CA3-LS-VTA) activates dopamine for contextual memory in animals, consistent with dopaminergic antagonist impairing declarative memory recall in humans; (e) whereas thiamine deficiency, the major nutritional deficit causing Wernicke-Korsakoff syndrome, impairs noradrenergic but spares dopaminergic system. Conclusion: It is supplemented the integrative dysfunctions in regulation of such neglected dopaminergic system, including the habenula, mammillary bodies and VTA dopamine, as partial contribution to memory impairments in Korsakoff’s syndrome.

What is the Korsakoff syndrome? – a paper in tribute to Prof Alwyn Lishman

ABSTRACT Introduction Alwyn Lishman was interested in how memory research could be applied to clinical psychiatry. After a brief review of his major contributions, this paper will focus on his research on the alcoholic Korsakoff syndrome. It will consider how his findings relate to contemporary debates, particularly on how the syndrome should be defined, and its relationship to broader alcohol-induced cognitive impairments. Methods A review of the contribution of Alwyn Lishman, Robin Jacobson and colleagues to our knowledge of Korsakoff’s syndrome, together with a review of the pertinent recent literature. Results Lishman and colleagues followed earlier authors in defining the Korsakoff syndrome in terms of disproportionate memory impairment, but they also noted a variable degree of IQ, frontal-executive, and timed visuo-spatial impairment in their cases. More recent authors have included such features in their definitions of the syndrome. Lishman also argued for a specific “alcoholic dementia”. The present paper argues that recent definitions of the Korsakoff syndrome confound its core and associated features, and also fail to recognise the multifactorial basis of alcohol-related brain damage. Conclusions Korsakoff’s syndrome is best defined in terms of disproportionate memory impairment, and more widespread cognitive impairment is best encompassed within “alcohol-related brain damage”.

The Relation between Behavioral, Emotional and Cognitive Apathy and Everyday Executive Dysfunction in Alcoholic Korsakoff’s Syndrome

ABSTRACT Background: Apathy is an important neuropsychiatric symptom in alcohol-related cognitive impairment in general, and Korsakoff’s syndrome in specific. However, research in patients with Korsakoff’s syndrome on the multifaceted nature of apathy is lacking. Objectives: Aim of the current study was to examine behavioral, cognitive and emotional apathy in alcoholic Korsakoff patients, also investigating the association with overall cognitive and executive dysfunction. Methods: We studied 43 patients with Korsakoff’s syndrome (mean age 60.9, SD=6.5, range 38-70) using the Apathy Evaluation Scale - Informant Version (AES-I) and also administered the Montreal Cognitive Assessment and the Behavior Rating Inventory of Executive Function - Adult Version (BRIEF-A) as a measure of daily executive problems. Results: In our sample, 76% of the Korsakoff patients were classified as being apathetic. AES-I scores correlated with overall cognitive function and were related to observer-rated daily executive problems. Discussion: Apathy is highly prevalent in Korsakoff patients and related to overall cognitive dysfunction and everyday executive problems. Our results stress the need to further examine underlying mechanisms of apathy in Korsakoff patients and the need for interventions aimed at reducing apathy.

Confabulations in Alcoholic Korsakoff's Syndrome: A Factor Analysis of the Nijmegen-Venray Confabulation List.

Confabulations generally refer to the emergence of memories of experiences and events that, in reality, never took place, and which are unintentionally produced. They are frequently observed in alcoholic Korsakoff’s syndrome. The aim of the current study was to validate the Nijmegen–Venray Confabulation List (NVCL), an observation scale for quantifying both spontaneous and provoked confabulations. The NVCL was completed for 252 patients with alcoholic Korsakoff’s syndrome. Exploratory and confirmatory factor analyses were conducted to test three- and four-factor models of the NVCL structure. A four-factor model (provoked confabulations, spontaneous confabulations, severity of spontaneous confabulations, and distorted sense of reality) fitted the data better than the initially proposed three-factor model (provoked confabulations, spontaneous confabulations, memory, and orientation). The new instrument is therefore referred to as the NVCL-R. We encourage clinicians to include the assessment of confabulations in the neuropsychological examination, and to do so with validated instruments such as the NVCL-R.

Preserved intellectual functioning in Korsakoff’s syndrome? Actual and premorbid intelligence in patients with major or mild alcohol-related cognitive disorder

ABSTRACTObjective: Although alcoholic Korsakoff patients show profound cognitive impairments (including amnesia), intellectual function has typically been assumed to be preserved. Based on more recent models on intelligence, however, it can be hypothesized that although preserved verbal or crystallized abilities may be expected in Korsakoff patients, fluid reasoning may be significantly reduced. Aim of this study was to gain insight in intelligence profiles of patients with alcohol-related cognitive disorders with and without Korsakoff’s syndrome (KS).Method: Test performance on the Wechsler Adult Intelligence Scale – Fourth Edition (WAIS-IV) and the National Adult Reading Test (NART) was assessed in 34 patients diagnosed with KS, 40 patients with chronic alcohol-related cognitive disorder without Korsakoff’s syndrome (ALC), and 47 non-alcoholic psychiatric controls (non-ALC).Results: Analysis revealed significant lower WAIS-IV Full-Scale IQ scores compared to the estimated premorbid NART-IQ in both groups with alcohol-related cognitive disorders (KS and ALC). With respect to the index scores, KS patients performed worse than non-ALC patients on the Perceptual Reasoning and Processing Speed Indices. Performance on the Verbal Comprehension and Working Memory Indices did not differ between groups.Conclusion: Not all aspects of intelligence are preserved in Korsakoff’s syndrome and implications of assessment of intellectual function in patients with alcohol-use disorder are discussed.

Chronic alcohol consumption and its effect on nodes of frontocerebellar and limbic circuitry: Comparison of effects in France and the United States

Alcohol use disorders present a significant public health problem in France and the United States (U.S.), but whether the untoward effect of alcohol on the brain results in similar damage in both countries remains unknown. Accordingly, we conducted a retrospective collaborative investigation between two French sites (Caen and Orsay) and a U.S. laboratory (SRI/Stanford University) with T1-weighted, structural MRI data collected on a common imaging platform (1.5T, General Electric) on 288 normal controls (NC), 165 uncomplicated alcoholics (ALC), and 26 patients with alcoholic Korsakoff's syndrome (KS) diagnosed at all sites with a common interview instrument. Data from the two countries were pooled, then preprocessed and analyzed together at the U.S. site using atlas-based parcellation. National differences indicated that thalamic volumes were smaller in ALC in France than the U.S. despite similar alcohol consumption levels in both countries. By contrast, volumes of the hippocampus, amygdala, and cerebellar vermis were smaller in KS in the U.S. than France. Estimated amount of alcohol consumed over a lifetime, duration of alcoholism, and length of sobriety were significant predictors of selective regional brain volumes in France and in the U.S. The common analysis of MRI data enabled identification of discrepancies in brain volume deficits in France and the U.S. that may reflect fundamental differences in the consequences of alcoholism on brain structure between the two countries, possibly related to genetic or environmental differences.

Applicability of the Rivermead Behavioural Memory Test – Third Edition (RBMT-3) in Korsakoff's syndrome and chronic alcoholics

PurposeTo examine the applicability of the newly developed Rivermead Behavioural Memory Test – Third Edition (RBMT-3) as an ecologically-valid memory test in patients with alcohol-related cognitive disorders.Patients and methodsAn authorized Dutch translation of the RBMT-3 was developed, equivalent to the UK version, and administered to a total of 151 participants – 49 patients with amnesia due to alcoholic Korsakoff’s syndrome, 49 patients with cognitive impairment and a history of chronic alcoholism, not fulfilling the Korsakoff criteria, and 53 healthy controls. Between-group comparisons were made at subtest level, and the test’s diagnostic accuracy was determined.ResultsKorsakoff patients performed worse than controls on all RBMT-3 subtests (all P-values < 0.0005). The alcoholism group performed worse than controls on most (all P-values < 0.02), but not all RBMT-3 subtests. Largest effects were found between the Korsakoff patients and the controls after delayed testing. The RBMT-3 had good sensitivity and adequate specificity.ConclusionThe RBMT-3 is a valid test battery to demonstrate everyday memory deficits in Korsakoff patients and non-Korsakoff patients with alcohol abuse disorder. Korsakoff patients showed an impaired performance on subtests relying on orientation, contextual memory and delayed testing. Our findings provide valuable information for treatment planning and adjustment in patients with alcohol-related cognitive impairments.

Function and Dysfunction of Prefrontal Brain Circuitry in Alcoholic Korsakoff’s Syndrome

The signature symptom of alcohol-induced persisting amnestic disorder, more commonly referred to as alcoholic Korsakoff's syndrome (KS), is anterograde amnesia, or memory loss for recent events, and until the mid 20th Century, the putative brain damage was considered to be in diencephalic and medial temporal lobe structures. Overall intelligence, as measured by standardized IQ tests, usually remains intact. Preservation of IQ occurs because memories formed before the onset of prolonged heavy drinking--the types of information and abilities tapped by intelligence tests--remain relatively well preserved compared with memories recently acquired. However, clinical and experimental evidence has shown that neurobehavioral dysfunction in alcoholic patients with KS does include nonmnemonic abilities, and further brain damage involves extensive frontal and limbic circuitries. Among the abnormalities are confabulation, disruption of elements of executive functioning and cognitive control, and emotional impairments. Here, we discuss the relationship between neurobehavioral impairments in KS and alcoholism-related brain damage. More specifically, we examine the role of damage to prefrontal brain systems in the neuropsychological profile of alcoholic KS.

002 Clinical varieties of memory disorders

: This talk will give an overview regarding clinical memory disorders. These encompass far more than just the dementias. Amnesic disorders can be transient or persisting. They can have a...

Morphological and Glucose Metabolism Abnormalities in Alcoholic Korsakoff's Syndrome: Group Comparisons and Individual Analyses

BackgroundGray matter volume studies have been limited to few brain regions of interest, and white matter and glucose metabolism have received limited research attention in Korsakoff's syndrome (KS). Because of the lack of brain biomarkers, KS was found to be underdiagnosed in postmortem studies.Methodology/Principal FindingsNine consecutively selected patients with KS and 22 matched controls underwent both structural magnetic resonance imaging and 18F-fluorodeoxyglucose positron emission tomography examinations. Using a whole-brain analysis, the between-group comparisons of gray matter and white matter density and relative glucose uptake between patients with KS and controls showed the involvement of both the frontocerebellar and the Papez circuits, including morphological abnormalities in their nodes and connection tracts and probably resulting hypometabolism. The direct comparison of the regional distribution and degree of gray matter hypodensity and hypometabolism within the KS group indicated very consistent gray matter distribution of both abnormalities, with a single area of significant difference in the middle cingulate cortex showing greater hypometabolism than hypodensity. Finally, the analysis of the variability in the individual patterns of brain abnormalities within our sample of KS patients revealed that the middle cingulate cortex was the only brain region showing significant GM hypodensity and hypometabolism in each of our 9 KS patients.Conclusions/SignificanceThese results indicate widespread brain abnormalities in KS including both gray and white matter damage mainly involving two brain networks, namely, the fronto-cerebellar circuit and the Papez circuit. Furthermore, our findings suggest that the middle cingulate cortex may play a key role in the pathophysiology of KS and could be considered as a potential in vivo brain biomarker.

The Korsakoff Syndrome: Clinical Aspects, Psychology and Treatment

The Korsakoff syndrome is a preventable memory disorder that usually emerges (although not always) in the aftermath of an episode of Wernicke's encephalopathy. The present paper reviews the clinical and scientific literature on this disorder. A systematic review of the clinical and scientific literature on Wernicke's encephalopathy and the alcoholic Korsakoff syndrome. The Korsakoff syndrome is most commonly associated with chronic alcohol misuse, and some heavy drinkers may have a genetic predisposition to developing the syndrome. The characteristic neuropathology includes neuronal loss, micro-haemorrhages and gliosis in the paraventricular and peri-aqueductal grey matter. Lesions in the mammillary bodies, the mammillo-thalamic tract and the anterior thalamus may be more important to memory dysfunction than lesions in the medial dorsal nucleus of the thalamus. Episodic memory is severely affected in the Korsakoff syndrome, and the learning of new semantic memories is variably affected. 'Implicit' aspects of memory are preserved. These patients are often first encountered in general hospital settings where they can occupy acute medical beds for lengthy periods. Abstinence is the cornerstone of any rehabilitation programme. Korsakoff patients are capable of new learning, particularly if they live in a calm and well-structured environment and if new information is cued. There are few long-term follow-up studies, but these patients are reported to have a normal life expectancy if they remain abstinent from alcohol. Although we now have substantial knowledge about the nature of this disorder, scientific questions (e.g. regarding the underlying genetics) remain. More particularly, there is a dearth of appropriate long-term care facilities for these patients, given that empirical research has shown that good practice has beneficial effects.

Do amnesic patients with Korsakoff’s syndrome use feedback when making decisions under risky conditions? An experimental investigation with the Game of Dice Task with and without feedback

We investigated the role of feedback processing in decision making under risk conditions in 50 patients with amnesia in the course of alcoholic Korsakoff’s syndrome (KS). Half of the patients were administered the Game of Dice Task (GDT) and the remaining 25 patients were examined with a modified version of the GDT in which no feedback was provided. Patients’ results in the GDT and in the modified version were compared with that of 50 healthy subjects of whom 25 subjects performed the original GDT and 25 performed the modified version. While performance on the original GDT was superior to performance on the modified GDT in healthy subjects, KS patients performed similarly on both the GDT with and GDT without feedback. Performance on both task versions was correlated with categorization and set-shifting. The findings indicate that amnesic patients do not profit from receiving feedback for their decisions in explicit risk conditions.

Confabulations in alcoholic Korsakoff patients

Besides forgetting, memory is also prone to distortions, errors and illusions. Confabulation is one type of memory distortion that may occur in cases of brain damage. Although confabulations are described anecdotally in patients with alcoholic Korsakoff syndrome (KS), there are few systematic investigations of the presence and nature of these types of false memories in KS. Moreover, it is unclear whether KS patients’ confabulations evenly affect all types of memories, or whether certain memory domains are more susceptible. Our study attempted to clarify two questions: first, whether confabulations are a critical feature of the cognitive impairment associated with long-term KS in a large sample of patients (N=42). Second, we investigated which memory domain is most likely affected by confabulations in KS. To elicit confabulations, we used a Confabulation Interview containing questions from different memory domains. We found that KS patients overall confabulated more compared to a group of healthy subjects. Furthermore, we found that patients confabulated most within the episodic/autobiographical memory domain.Our results imply that besides pronounced memory deficits typically associated with KS, confabulation can also be regarded as a clinical feature of the disease. The preponderance of episodic confabulation obtained here by using a standardized test, confirms anecdotic reports that KS patients confabulate in everyday life mainly with respect to their personal past and present.Thus, for a detailed description of the memory profile of KS patients, the screening of confabulation tendencies may be a useful supplementary clinical tool.

Episodic and Working Memory Deficits in Alcoholic Korsakoff Patients: The Continuity Theory Revisited

The exact nature of episodic and working memory impairments in alcoholic Korsakoff patients (KS) remains unclear, as does the specificity of these neuropsychological deficits compared with those of non-Korsakoff alcoholics (AL). The goals of the present study were therefore to (1) specify the nature of episodic and working memory impairments in KS, (2) determine the specificity of the KS neuropsychological profile compared with the AL profile, and (3) observe the distribution of individual performances within the 2 patient groups. We investigated episodic memory (encoding and retrieval abilities, contextual memory and state of consciousness associated with memories), the slave systems of working memory (phonological loop, visuospatial sketchpad and episodic buffer) and executive functions (inhibition, flexibility, updating and integration abilities) in 14 strictly selected KS, 40 AL and 55 control subjects (CS). Compared with CS, KS displayed impairments of episodic memory encoding and retrieval, contextual memory, recollection, the slave systems of working memory and executive functions. Although episodic memory was more severely impaired in KS than in AL, the single specificity of the KS profile was a disproportionately large encoding deficit. Apart from organizational and updating abilities, the slave systems of working memory and inhibition, flexibility and integration abilities were impaired to the same extent in both alcoholic groups. However, some KS were unable to complete the most difficult executive tasks. There was only a partial overlap of individual performances by KS and AL for episodic memory and a total mixture of the 2 groups for working memory. Korsakoff's syndrome encompasses impairments of the different episodic and working memory components. AL and KS displayed similar profiles of episodic and working memory deficits, in accordance with neuroimaging investigations showing similar patterns of brain damage in both alcoholic groups.

Cognitive performance of detoxified alcoholic Korsakoff syndrome patients remains stable over two years

Excessive alcohol consumption is assumed to promote cognitive decline, eventually increasing the risk of dementia. However, little is known about the time course of cognitive functions in patients with chronic alcoholic Korsakoff syndrome (KS). Therefore, we assessed neuropsychological performance in 20 detoxified chronic KS inpatients at time 1 (T1) with a follow-up after two years (T2). The neuropsychological tests assessed verbal and visual short- and long-term memory, working memory, basic executive functions, language, general knowledge, and visual–spatial abilities. Surveys with caregivers and medical records provided information about current and previous disease-related parameters, drinking history, additional pathologies, as well as psychosocial and cognitive therapy within the two-year period. At both sessions, the majority of the KS patients' results were inferior to those of normal subjects. Comparing T1 and T2 revealed no significant decline in any of the investigated functions. Instead, general knowledge, visual long-term memory, and verbal fluency improved slightly after two years, though they still remained within pathological range. Comparing most improved and most deteriorated patients, better outcome occurred more frequently in men than women and was associated with higher premorbid education and fewer detoxifications in the past. In this sample of detoxified KS patients there was no indication of accelerated cognitive decline or onset of dementia-like symptoms over two years.

Judgment and memory performance for emotional stimuli in patients with alcoholic Korsakoff syndrome

In this study we investigated whether alcoholic Korsakoff patients are impaired in categorizing neutral and emotional stimuli according to their valence and whether memory performance for this material is reduced. In a group of Korsakoff patients and a comparison group two experimental tasks—one containing emotional and neutral pictures and the other containing words—were administered. Results showed that patients had difficulties in affective judgments due to problems in classifying neutral stimuli. Memory for emotional and neutral material was impaired to a similar degree. Thus, the facilitating effect of emotional valence on memory performance is absent in Korsakoff patients.

Cognitive profile of patients with alcoholic Korsakoff's syndrome

Presents an overview of empirical research on cognitive dysfunctions characteristic of alcoholic Korsakoff's syndrome (KS). Recent evidence shows that, apart from severe anterograde and retrograde memory deficits, Korsakoff's pathology can include pronounced emotional abnormalities and impairments in executive functioning (e.g., problem solving, cognitive flexibility, set shifting, and task monitoring). Neurological studies have consistently revealed lesions in diencephalic and prefrontal brain areas among KS patients. It is assumed that damage in mammillary regions and the thalamus are determinants of amnesic symptoms, whereas observed executive dysfunctions more likely result from damage in the prefrontal lobe. Future research will more closely examine the causes of brain changes in KS, discerning between the primary neurotoxic effects of alcohol consumption on the one hand, and the secondary effects of malnutrition and/or vitamin deficiencies on the other. A further topic of inquiry will concern symptom specificity in KS, alcohol-addiction, and alcohol-related dementia.

Visuoperceptual Learning in Alcoholic Korsakoff Syndrome

Relative to the characteristically profound deficits of explicit memory, components of implicit memory remain largely intact in patients with alcohol-induced Korsakoff syndrome (KS). Perceptual priming occurs in KS and transfer of learning has been consistently observed on mirror reading, a perceptual reversal task. Although priming also occurs with fragmented pictures, a perceptual closure task, it is unclear whether transfer of learning can occur. This study examined visuoperceptual learning in 4 men with alcoholic KS, 9 recently detoxified alcoholic men (ALC), 21 healthy age-matched normal control men (NC), and 6 young normal control men (YNC). Subjects were tested with the Gollin Incomplete Pictures Test at initial and 1-hour and 1-day retest sessions. Both alcoholic groups (KS, ALC) were impaired in visuoperceptual ability. All subject groups showed visuoperceptual learning. The KS group showed additional learning after continued exposure to the stimuli, despite their nonmnemonic visuospatial deficits and profound explicit memory impairment for the test stimuli. Transfer of learning to similar but new stimuli was not evident in either the KS or young healthy control subjects; learning occurred only for the specific items presented. The persistence of learning beyond the life of the percept, which was independent of declarative features (such as item recall), suggests that perceptual learning and memory reflects an intact cognitive memory process in KS. This process is likely mediated by posterior cortical networks relatively unaffected in KS and that are independent of the hippocampal-diencephalic declarative memory system.

Decision-Making Deficits of Korsakoff Patients in a New Gambling Task With Explicit Rules: Associations With Executive Functions.

Decision-making deficits reflected by risky decisions in gambling tasks have been associated with frontal lobe dysfunctions in various neurologic and psychiatric populations. The question remains whether decision-making impairments are related to executive functions. The authors developed a new gambling task, the Game of Dice Task, with explicit and stable rules for reinforcement and punishment, to investigate relations between executive functions and risk-taking behavior in an explicit decision-making situation. A sample of 35 alcoholic Korsakoff patients and 35 healthy controls was examined with the Game of Dice Task and a neuropsychological test battery. Results show that Korsakoff patients are strongly impaired in this explicit decision-making task and that these disturbances are correlated with specific executive functions.

Interaction Between Emotion and Memory: Importance of Mammillary Bodies Damage in a Mouse Model of the Alcoholic Korsakoff Syndrome

Chronic alcohol consumption (CAC) can lead to the Korsakoff syndrome (KS), a memory deficiency attributed to diencephalie damage and/or to medial temporal or cortical related dysfunction. The etiology of KS remains unclear. Most animal models of KS involve thiaminedeficient diets associated with pyrithiamine treatment. Here we present a mouse model of CAC-induced KS. We demonstrate that CAC-generated retrieval memory deficits in working/ episodic memory tasks, together with a reduction of fear reactivity, result from damage to the mammillary bodies (MB). Experimental lesions of MB in non-alcoholic mice produced the same memory and emotional impairments. Drugs having anxiogenic-like properties counteract such impairments produced by CAC or by MB lesions. We suggest (a) that MB are the essential components of a brain network underlying emotional processes, which would be critically important in the retrieval processes involved in working/ episodic memory tasks, and (b) that failure to maintain emotional arousal due to MB damage can be a main factor of CAC-induced memory deficits. Overall, our animal model fits well with general neuropsychological and anatomic impairments observed in KS.