Wernicke-Korsakoff Research Articles

From wernicke-korsakoff to central pontine myelinolysis: the potentially irreversible risks of alcohol use

Introduction Sustained alcohol intake, when combined with incomplete treatment, can result in chronic structural changes in the Central Nervous System, including generalized cortical and cerebellar atrophy, amnesic syndromes like Korsakoff’s syndrome, and white matter disorders such as Central Pontine Myelinolysis and Marchiafava-Bignami syndrome. It is crucial to prevent these complications due to their potential for irreversible and debilitating consequences. For Wernicke-Korsakoff syndrome, early recognition and thiamine administration for prevention are paramount, as it arises from thiamine deficiency due to malnutrition caused by persistent alcohol use. In the case of Central Pontine Myelinolysis, which is caused by abrupt fluctuations in serum osmolality, controlled sodium correction is essential.ObjectivesThrough a clinical case and a review of published literature, this study aims to reflect on the importance of preventing neurological injuries associated with chronic alcohol consumption, specifically Wernicke-Korsakoff Syndrome and Central Pontine Myelinolysis.Methods A literature review was conducted by searching for articles on PubMed using the terms “Alcohol Use Disorder,” “Wernicke-Korsakoff syndrome,” and “Central pontine myelinolysis.” A clinical case is presented, featuring a 50-year-old patient with alcohol use disorder who developed Wernicke-Korsakoff syndrome and Central Pontine Myelinolysis. Considering this case, we reflect on the primary approaches that could have been beneficial in preventing these complications and propose a straightforward method for doing so.Results A 50-year-old patient presented with poor general condition, characterized by low weight, significant loss of strength in the limbs and arms, and incoherent speech with anterograde amnesia and confabulation. This condition had progressed to a point where the patient could no longer walk, perform basic self-care tasks such as bathing, dressing, and eating independently, underscoring the severity of his condition. The diagnoses of Wernicke-Korsakoff syndrome and Central Pontine Myelinolysis were established based on clinical manifestations and the presence of hyperintense lesions observed in the central pons on T2/FLAIR axial MRI scans. This clinical case highlights the importance of proper and precocious prevention of complications in patients with alcohol use disorder. The foremost step in preventing these complications is to treat alcohol dependence effectively, even when faced with patient resistance. It’s vital to remain vigilant about potential complications and implement suitable prophylactic measures.ConclusionsThe devastating effects of complications arising from Alcohol Use Disorder, such as Wernicke-Korsakoff syndrome and Central Pontine Myelinolysis, underscore the importance of enhanced attention that clinicians should provide when approaching these patients at all clinical interactions.Disclosure of InterestNone Declared

Relationship between alcohol consumption and dementia with Mendelian randomization approaches among older adults in the United States.

In observational studies, the association between alcohol consumption and dementia is mixed. We performed two-sample Mendelian randomization (MR) using summary statistics from genome-wide association studies of weekly alcohol consumption and late-onset Alzheimer's disease and one-sample MR in the Health and Retirement Study (HRS), wave 2012. Inverse variance weighted two-stage regression provided odds ratios of association between alcohol exposure and dementia or cognitively impaired, non-dementia relative to cognitively normal. Alcohol consumption was not associated with late-onset Alzheimer's disease using two-sample MR (odds ratio [OR]=1.15, 95% confidence interval [CI]: [0.78, 1.72]). In HRS, doubling weekly alcohol consumption was not associated with dementia (African ancestries, n=1,322, OR=1.00, 95% CI [0.45, 2.25]; European ancestries, n=7,160, OR=1.37, 95% CI [0.53, 3.51]) or cognitively impaired, non-dementia (African ancestries, n=1,322, OR=1.17, 95% CI [0.69, 1.98]; European ancestries, n=7,160, OR=0.75, 95% CI [0.47, 1.22]). Alcohol consumption was not associated with cognitively impaired, non-dementia or dementia status. Cross-sectionally in a large, diverse sample, alcohol appears protective for dementia.We apply two- and one-sample Mendelian randomization to test inferred causality.Mendelian randomization approaches show no association with alcohol and dementia.We conclude that alcohol consumption should not be considered protective.

The Role of Alcohol Use Disorders in the Development and Progression of Dementia

IntroductionIn recent years, there has been an increase in interest and research into the link between alcohol use disorders (AUD) and dementia. Alcohol use disorders, which are characterised by excessive and problematic alcohol consumption, have been associated to a variety of detrimental health effects, including liver disease, cardiovascular difficulties, and cognitive impairments.ObjectivesTo explore the link between alcohol use disorders and dementia onset and progression, explaining probable causes and emphasising preventive approaches.Methods The present study involved a thorough examination of relevant research papers, with a specific emphasis on longitudinal cohort studies, neuropathological observations, and biochemical interactions pertaining to the effects of alcohol on the brain. In addition to the aforementioned criteria, the review also took into account other complicating factors, including choices regarding lifestyle, genetic predisposition, and coexisting medical conditions.Results The results indicate a strong association between prolonged and excessive alcohol consumption and a heightened susceptibility to the early onset of dementia. The mechanisms underlying alcohol-related neurological damage encompass direct neurotoxic effects of alcohol, thiamine shortage, and alcohol-related cerebrovascular illness. Moreover, it is worth noting that alcohol use disorder (AUD) has the potential to worsen the advancement of neurodegenerative processes in individuals already diagnosed with dementia.ConclusionsThe association between AUD (Alcohol Use Disorder) and dementia is complex and involves multiple factors, presenting considerable difficulties in terms of clinical intervention and treatment. The use of early intervention strategies and public health initiatives focused on addressing alcohol use disorder (AUD) could have a significant impact on preventing or reducing the development of dementia.Disclosure of InterestNone Declared

Tanshinone IIA Alleviates Traumatic Brain Injury by Reducing Ischemia‒Reperfusion via the miR-124-5p/FoxO1 Axis.

Cerebral ischemia-reperfusion injury is a common complication of ischemic stroke that affects the prognosis of patients with ischemic stroke. The lipid-soluble diterpene Tanshinone IIA, which was isolated from Salvia miltiorrhiza, has been indicated to reduce cerebral ischemic injury. In this study, we investigated the molecular mechanism of Tanshinone IIA in alleviating reperfusion-induced brain injury. Middle cerebral artery occlusion animal models were established, and neurological scores, tetrazolium chloride staining, brain volume quantification, wet and dry brain water content measurement, Nissl staining, enzyme-linked immunosorbent assay, flow cytometry, western blotting, and reverse transcription-quantitative polymerase chain reaction were performed. The viability of cells was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assays, while cell damage was measured by lactate dehydrogenase release in the in vitro oxygen glucose deprivation model. In addition, enzyme-linked immunosorbent assay, flow cytometry, western blotting, and reverse transcription-quantitative polymerase chain reaction were used to evaluate the therapeutic effect of Tanshinone IIA on ischemia/reperfusion (I/R) induced brain injury, as well as its effects on the inflammatory response and neuronal apoptosis, in vivo and in vitro. Furthermore, this study validated the targeting relationship between miR-124-5p and FoxO1 using a dual luciferase assay. Finally, we examined the role of Tanshinone IIA in brain injury from a molecular perspective by inhibiting miR-124-5p or increasing FoxO1 levels. After treatment with Tanshinone IIA in middle cerebral artery occlusion-reperfusion (MCAO/R) rats, the volume of cerebral infarction was reduced, the water content of the brain was decreased, the nerve function of the rats was significantly improved, and the cell damage was significantly reduced. In addition, Tanshinone IIA effectively inhibited the I/R-induced inflammatory response and neuronal apoptosis, that is, it inhibited the expression of inflammatory cytokines IL-1β, IL-6, TNF-α, decreased the expression of apoptotic protein Bax and Cleaved-caspase-3, and promoted the expression of antiapoptotic protein Bcl-2. In vitro oxygen-glucose deprivation/reoxygenation (OGD/R) cell model, Tanshinone IIA also inhibited the expression of inflammatory factors in neuronal cells and inhibited the occurrence of neuronal apoptosis. In addition, Tanshinone IIA promoted the expression of miR-124-5p. Transfection of miR-124-5p mimic has the same therapeutic effect as Tanshinone IIA and positive therapeutic effect on OGD cells, while transfection of miR-124-5p inhibitor has the opposite effect. The targeting of miR-124-5p negatively regulates FoxO1 expression. Inhibition of miR-124-5p or overexpression of FoxO1 can weaken the inhibitory effect of Tanshinone IIA on brain injury induced by I/R, while inhibition of miR-124-5p and overexpression of FoxO1 can further weaken the effect of Tanshinone IIA. Tanshinone IIA alleviates ischemic-reperfusion brain injury by inhibiting neuroinflammation through the miR-124-5p/FoxO1 axis. This finding provides a theoretical basis for mechanistic research on cerebral ischemia-reperfusion injury.

Personality traits and personality problems in Korsakoff syndrome patients

ABSTRACT Personality research is of relevance because it provides insights into the psychological strengths and vulnerabilities of a person. Korsakoff’s syndrome (KS) is a severe neuropsychiatric disorder following acute thiamine deficiency, usually as a consequence of alcohol-use disorders. Research on personality traits of KS patients is currently limited. The aim of the current exploratory study was therefore to examine the personality traits and problems of KS patients. We assessed self-reported and informant-reported personality traits and problems in institutionalized KS patients (n = 30). Results indicate that the psychotic personality organization was more frequently present in KS patients compared to a psychiatric reference population, leading to increased vulnerability for the development of severe psychiatric issues. Informants observed more premorbid and current cluster B (“emotional”) and C (“anxious”) personality behavior in comparison to the general population. Also, rigid- and socially avoidant behavior in KS patients was observed to increase over the years. They also observed personality problems such as emotional-, unpredictable-, dramatic-, anxious and fearful behavior in the present and in the past. KS patients reported themselves as healthy individuals, indicating a lack of self-awareness. We recommend training programs for the medical team focussed on psycho-education and supportive interventions for patients with complex personality problems concomitant to KS.

Sociodemographic and Clinical Predictors of Prolonged Length of Corneal Ulcer Hospitalizations

The length of stay (LOS) of hospitalizations may be a useful indicator of the burden of disease of corneal ulcers. Identifying variables associated with longer LOS may help to enhance delivery of care for high-risk patients. To investigate the sociodemographic, social, and clinical factors associated with LOS in hospitalizations for corneal ulcers in the US. This was a retrospective cross-sectional study of adult patients (aged >18 years) admitted with a primary diagnosis of corneal ulcer between quarter 4 of 2015 through 2020 and conducted using data from the National Inpatient Sample (NIS). Patients were stratified into 2 even cohorts based on LOS: LOS of 4 days or less and LOS greater than 4 days. Individual-level sociodemographic, social risk factors, and medical comorbidities associated with longer LOS were examined by multivariable regression. Data were analyzed from October 2015 to December 2020. Potential sociodemographics or medical comorbidities at hospital admission. The primary outcome of interest was factors associated with extended length of stay. The hypothesis being tested was formulated during data collection. A total of 1187 patients (mean [SD] age, 53.5 [20.9] years; 602 female [50.7%]) were included for analysis. The cohort with LOS greater than 4 days had higher total charges than the cohort with LOS of 4 days or less (mean [SD] charges, $79 504 [$86 719] vs $26 474 [$20 743]; P < .001). Sociodemographic variables associated with LOS greater than 4 days were Black race (adjusted odds ratio [aOR], 1.41; 95% CI, 1.03-1.92; P = .03), Medicare insurance (aOR, 1.42; 95% CI, 1.09-1.85; P = .009), and housing insecurity (aOR, 1.99; 95% CI, 1.29-3.06; P = .002). Medical comorbidities associated with LOS greater than 4 days were alcohol use (aOR, 1.50; 95% CI, 1.00-2.26; P = .05), dementia (aOR, 2.35; 95% CI, 1.36-4.07; P = .002), complicated diabetes (aOR, 1.75; 95% CI, 1.21-2.53; P = .003), uncomplicated diabetes (aOR, 1.57; 95% CI, 1.02-2.42; P = .04), drug misuse (aOR, 1.66; 95% CI, 1.08-2.57; P = .02), and legal blindness (aOR, 3.42; 95% CI, 1.19-9.82; P = .02). Based on NIS national estimates, corneal ulcers were estimated to have a direct annual health care expenditure of $35 819 590 in the US. Corneal ulcer hospitalizations represent a significant burden of disease for patients and health care systems. This study highlights sociodemographic and clinical factors that may help clinicians identify high-risk patients vulnerable to complications and morbidity due to corneal ulcers.

Measuring episodic verbal learning ability in alcohol-related cognitive disorders in relation to everyday functioning

Adequate and timely assessment of learning abilities in individuals with alcohol-related cognitive disorders is highly relevant to optimize addiction care. Learning curves of episodic verbal memory tests have been used to assess learning ability in various neurocognitive disorders, but studies in alcohol-related cognitive disorders are lacking. Therefore, this study investigated California Verbal Learning Test (CVLT) learning curves in individuals with alcohol-use disorder (AUD) with and without cognitive impairments and examined associations between learning curves and changes in everyday functioning following a multicomponent care program. We fitted learning curves over the five immediate recall trials of the Dutch version of the CVLT of patients with Korsakoff's syndrome (KS; N = 117), alcohol-related cognitive impairment no KS (ARCI; N = 147), and uncomplicated AUD (N = 43) using a generalized non-linear mixed regression. This model was based on three different parameters: initial memory performance (attention), maximum number of correctly recalled words (maximum learning), and the increase of correctly recalled words over the trials (learning rate). Next, we related these learning curves with ratings of everyday activities using the Patient Competency Rating Scale (PCRS) before and after a care program following admission. Modelled learning curves differed across groups, with significant differences in Attention (KS<ARCI<AUD, p < 0.001), Maximum Learning (KS<ARCI<AUD, p<0.001), and Learning Rate (KS<ARCI=AUD, p < 0.001). However, modelled learning curves were not related to reliable improvement in PCRS scores (p>0.05). Although modelled learning curves may be used to differentiate diagnostic groups in alcohol-related cognitive disorders, future studies are needed to establish the criterion validity of learning curves in this population.

"Do not take that medication": negative prospective memory in Korsakoff's syndrome.

While prospective memory (i.e., the ability to execute a future plan) has been extensively researched, little is known about negative prospective memory (i.e., the ability to remember not to execute a future plan) in Korsakoff's syndrome (KS). We thus evaluated both prospective memory and negative prospective memory in KS, as well as the relationship between both types of prospective memory and inhibition. Patients with KS and control participants were invited to press a button on the keyboard (i.e., prospective memory) or not to press a button when a cue word (e.g., negative prospective memory) was encountered. The analysis demonstrated that patients with KS had more prospective memory errors (i.e., forgetting to click the keyboard when the instruction was to do so) than control participants. The analysis also demonstrated that patients with KS had more negative prospective memory errors (i.e., clicking the keyboard when the instruction was not to do so) than control participants. Similar levels of commissions and omissions were observed in patients with KS than in control participants. Interestingly, prospective and negative prospective performances were significantly correlated with performance on an inhibition assessment task. Our study demonstrates that KS is characterized by not only difficulty in remembering to execute a future intention but also by difficulty in remembering not to execute a future intention. A decline in negative prospective memory in KS can be associated with difficulty in inhibiting no longer appropriate previously learned intentions.

Hemosiderin Detection inside the Mammillary Bodies Using Quantitative Susceptibility Mapping on Patients with Wernicke-Korsakoff Syndrome.

Hemorrhage inside the mammillary bodies (MMBs) is known to be one of the findings of Wernicke encephalopathy. Brain MRI of two patients with Wernicke-Korsakoff syndrome (WKS) demonstrated high susceptibility values representing hemosiderin deposition in MMBs by using quantitative susceptibility mapping (QSM). QSM provided additional information of susceptibility values to susceptibility-weighted imaging in diagnosis of WKS.

Clinical Heterogeneity in Alzheimer's Disease: A Possible New Amnesic Phenotype.

We rediscovered a phenotype of AD known in the early 1900s as presbyophrenia, but then forgotten, and renamed as confabulation-misidentification phenotype. The phenotype includes diencephalic amnesia whose prototype is Korsakoff syndrome. The main features are anterograde and retrograde amnesia with marked disorientation and confabulation, executive impairments, reduced insight and attention deficits, misidentification, minor hallucination and other delusions, behavioral disturbances, and early anxiety. In this article, we summarize what we have discovered about the new phenotype and what is still missing to confirm this diencephalic variant of AD.

Hospital Outcomes in Medical Patients With Alcohol-Related and Non–Alcohol-Related Wernicke Encephalopathy

ObjectiveTo conduct a nationwide retrospective cohort study to assess trends and hospitalization-associated outcomes in patients with Wernicke encephalopathy. Patients and MethodsIn this nationwide retrospective cohort study, we used in-hospital claims data of patients hospitalized with Wernicke encephalopathy in Switzerland from January 1, 2012, to December 31, 2020. We estimated incidence rates per 100,000 person-years among the overall Swiss population stratified by alcohol and non–alcohol-induced Wernicke encephalopathy. The primary outcome was all-cause in-hospital mortality. Secondary outcomes included progression to Korsakoff syndrome and 1-year hospital readmission. We estimated odds ratios (ORs) for binary outcomes. ResultsIt was found that 4098 of 4393 hospitalizations (93.3%) for Wernicke encephalopathy during the 8-year study were alcohol-related. Incidence rates for hospitalizations were 14-fold higher in alcohol-related compared with non–alcohol-related Wernicke encephalopathy (5.43 vs 0.39 per 100,000 person-years). The risk for in-hospital mortality was significantly lower in patients with alcohol-related vs non–alcohol-related Wernicke encephalopathy (3.2% vs 8.5%; adjusted OR, 0.38; 95% CI, 0.23 to 0.62). Patients with alcohol-related Wernicke encephalopathy had higher risk for development of Korsakoff syndrome (16.9% vs 1.7%; adjusted OR, 10.64; 95% CI, 4.37 to 25.92) and 1-year hospital readmission (31.6% vs 18.7%; adjusted OR, 1.4; 95% CI, 1.04 to 1.88). ConclusionIn this Swiss nationwide cohort study, Wernicke encephalopathy was a rare but serious cause for hospitalization and mainly alcohol-related. Patients with alcohol-related Wernicke encephalopathy had lower risks of in-hospital mortality but were more likely to develop Korsakoff syndrome and be readmitted to the hospital.

Compliance with Glasgow Modified Alcohol Withdrawal Scale Guidelines within Emergency Medicine Utilising Electronic Prescribing Protocols

Abstract Introduction Glasgow Modified Alcohol Withdrawal Scale (GMAWS) allows evidence-based management of patients at risk of alcohol withdrawals within the hospital setting. Adherence to this guideline mitigates risk of patients developing Wernicke-Korsakoff syndrome, a neurological disorder resulting from a thiamine deficiency induced by chronic alcohol consumption1. As Scotland has particularly high rates of alcohol misuse, utilisation of this guideline avoids development of this serious complication with a large at-risk population. However, non-compliance and incorrect prescribing has been prevalent as this can be difficult and time-consuming to manually prescribe leading to errors. This can be avoided by utilising the novel electronic prescribing protocol on Hospital Electronic Prescribing and Medicine Administration (HEPMA) programme. Aim The aim of this quality improvement project was to increase compliance with the GMAWS guideline and ensure correct prescribing within Emergency Medicine. Methods Data collection was supported by the HEPMA team, with daily reports of all identified patients to allow evaluation of GMAWS prescribing as per protocols. Identified patients were confirmed to be on GMAWS and not prescribed thiamine/benzodiazepines for another indication with presence of GMAWS paper chart. Data was initially collected over a two-week period to establish a baseline, with further two-week periods of data collection after interventions. Intervention 1 was distribution of a hospital wide memo regarding GMAWS protocol. Intervention 2 was buzzword teaching on GMAWS with small groups of prescribers. This study did not require ethics approval due to it being a service evaluation / improvement project. Results The data collection following interventions demonstrated improved compliance with HEPMA protocols, evidenced by an increase from 33.3% at baseline to 82.1% compliance. The intervention of buzzword teaching was most impactful with 82.1% compliance recorded following this. An overall increase of 55.6% in the total prescribing of GMAWS signifies an increased awareness of the guidelines and increased confidence with prescribing. Discussion/Conclusion As novel electronic prescribing continues to evolve, pharmacy is a main contributor for advocating optimised prescribing and supporting best practice. Significant learning points included that many patients were on unnecessarily prolonged courses of parental thiamine, which has significant cost and nursing time implications. This is supported by the fact that oral thiamine costs 0.5% of the total cost of giving parental thiamine daily and reduced risks from unnecessary prolonged cannulation. We were able to incorporate this learning into the buzzword teaching to prompt review of parental thiamine prescribed without a clear duration. This project has prompted a review of our health board’s GMAWS guideline to streamline and update guidance in line with updated NICE guidelines. Feedback from the buzzword teaching sessions has been incorporated to improve readability and aid use, via the rationalisation of the GMAWS paperwork. The corresponding HEPMA protocols will then be updated to reflect these changes. Furthermore, this work has influenced other specialities to create and teach the use of HEPMA protocols to optimise treatment.

Alcohol-related dementia

Dementia is one of the leading causes of death both in the UK and worldwide. Approximately 1 million people have been diagnosed with this condition in the UK. Although there are many types of dementia, this article will focus on alcohol-related dementia. Alcohol has become a leading cause of death in the 50−69-year age group in England, and with consumption rising rapidly, there is an increased risk that young and middle-aged people will develop alcohol-related dementia in the future. The aim of this article is to review the evidence base and discuss whether alcohol-related dementia is a sub-class of dementia or a separate entity.

47 Social Cognition and Moral Decision Making in Korsakoff's Syndrome

Objective:Korsakoff's syndrome (KS) is a neuropsychiatric disorder, caused by vitamin B1 insufficiency. KS is characterized by severe declarative amnesia. Often, also executive disorders are present. Emotion recognition and theory of mind are gold-standard measures of social cognition. Moral decision making is often assessed by means of moral dilemmas. Surprisingly social cognition and moral decision making has received hardly any attention in research on KS, although the severity of behavioural problems in KS suggest possible problems in both domains. The aim of this study was therefore to broadly assess social cognition and moral decision-making capacities in patients with KS.Participants and Methods:20 KS patients and 20 age-, education-, and gender-matched healthy controls were assessed on standardized tests for social cognition, namely the mini-Social Cognition and Emotional Assessment battery (mini-SEA), and a specialized version of the Sally-Anne Test. Moral decision making was assessed by means of the Moral Behaviour Inventory (MBI) for everyday moral dilemmas, and ten cartoons of abstract moral dilemmas. For moral decision making, “yes” and “no” responses were scored, together with a scoring for moral reasoning according to the Kohlberg stages of moral maturity.Results:KS patients have large impairments in both cognitive and affective aspects of social cognition. Their ability to recognize emotions, take the perspective of others, and understand socially awkward situations is vastly compromised. While KS patients were able to replicate the Sally Anne storyline, their task performance was on chance level. Regarding moral decision making, there was a tendency to more frequently carry out the moral dilemma. Moral maturity, as indexed by means of their reasoning behind the decision was of a lower level. Of interest, moral immaturity could find its origin already before the onset of the KS diagnosis, as suggested by elevated premorbid levels of delinquent behavior.Conclusions:Both social cognition and moral decision making are compromised in KS patients. Specifically social cognitive disorders are the direct result of KS, and are likely to strongly relate to social and neuropsychiatric issues in KS. Moral decision making was more likely to be already of a lower level of maturity, based on a strong relationship between premorbid delinquency and moral immaturity in KS patients. This study highlights the importance to properly index social cognition in neuropsychological assessments for individuals with a possible KS diagnosis

26 Apathy in Korsakoff Patients with and without Neurovascular Comorbidity

Objective:People with Korsakoff syndrome (KS) experience severe neuropsychological and neuropsychiatric complications following vitamin B1 deficiency predominantly due to alcoholism. KS often presents itself with neuropsychological symptoms such as problems in episodic memory, executive functioning, and social cognition. Common neuropsychiatric symptoms in KS are disorders of affect, confabulations, anosognosia, and apathy. Apathy can be defined by a pathological lack of goal-directed behaviors, goal-directed cognitions, and goal-directed emotions. Patients with KS have an increased risk of cerebrovascular comorbidity. Cerebrovascular accidents are known to increase the risk for developing apathy. Apathy in KS patients can negatively influence the ability to live an autonomous life, often making 24-hour care a necessity. Limited research on apathy in KS patients has been published to this day. Our aim was to assess apathy in Korsakoff patients with and without neurovascular comorbidity.Participants and Methods:General apathy and related subconstructs, such as judgment and decision-making skills, emotional blunting, and the intentions to perform pleasurable activities, were studied in fifteen KS patients, fifteen KS patients with additional cerebrovascular comorbidity, and fifteen healthy controls. The first responsible caregiver of each patient filled in the Apathy Evaluation Scale and Scale for Emotional Blunting. An examiner administered the interview-based Judgement scale of the Neuropsychology Assessment Battery with the KS patients and each KS patient filled in the self-report section of the Pleasurable Activities List. Both KS patient groups receive 24-hour care in a specialized facility for Korsakoff Syndrome.Results:Our study found higher levels of general apathy in both KS patient groups, when rated by their caregiver compared to healthy controls. No difference was found between the KS patient groups and the healthy control group on the self-reported section of the Pleasurable Activities List, which might suggest the presence of intrinsic motivation in KS patients. However, a discrepancy was found between the self-reported activity levels and proxy reported levels of apathy. KS patients with cerebrovascular comorbidity showed increased levels of emotional blunting compared to KS patients without cerebrovascular comorbidity and healthy controls. Decreased judgment and decision-making skills were found in both patient groups compared to healthy controls, with no difference found between KS patients with cerebrovascular comorbidity and KS patients without.Conclusions:Our findings suggest that people with Korsakoff syndrome experience more general apathy compared to healthy controls. Both patient groups showed decreased judgement and decision-making skills and increased emotional blunting. Intrinsic motivation was found to be intact in KS patients. Experiencing cerebrovascular comorbidity in KS carries a risk for developing emotional blunting. Our findings show that apathy greatly affects people with KS. Future scientific research is warranted to further benefit the care for this complex patient population.

85 Smartwatch reminders support prospective memory in Korsakoff’s syndrome

Objective:Korsakoff’s syndrome (KS) is a neuropsychiatric disorder, caused by malnutrition. Central to KS are severe amnesia and executive dysfunctions. KS patients often fail to remember future intentions (prospective memory),and rely heavily on external support by caregivers. Recently, specialized smartwatches have been developed to support prospective memory verbally and by displaying pictures of future events. We investigated the benefit of a smartwatch and smartphone compared to no aid in supporting time accuracy and the ability to carry out future intentions in one case study. In three subsequent case studies, we investigated the possible benefits of a smartwatch aid for prospective memory (PM) compared to verbal in-person reminders.Participants and Methods:In the first case study, one high-functioning KS patient with a WAIS IQ of 127 points, performed a total of 36 novel prospective memory tasks in three conditions (smartwatch, smartphone and no-aid).In the second case series, three KS patients with average IQ performed 30 everyday PM tasks in two conditions (smartwatch, in-person).Two dependent variables were indexed in both studies: PM time accuracy (in minutes), this was calculated as minutes difference from the assigned time, and precision of the PM task (correct or incorrect).Results:In the first study, time accuracy was improved with a smartwatch compared to a smartphone and no-aid condition. Furthermore, the smartwatch and smartphone conditions were more effective than no aid in assisting memory for task content. In the second study, both the smartwatch and in-person instructions were equally effective in supporting prospective memory tasks.Conclusions:Since prospective memory is compromised in KS, patients require assistance throughout the day in performing everyday and non-everyday tasks. The results of our case studies suggest that a smartwatch that gives specific verbal and visual reminders can be particularly helpful in supporting prospective memory for KS patients. Giving in-person instructions was equally effective as the use of this smartwatch, highlighting the possibility to support KS patients with less intensive everyday coaching. Together, these results are promising in applying smartwatches clinically to support prospective memory.

Over a Century of Study and Still Misunderstood: Recognizing the Spectrum of Acute and Chronic Wernicke–Korsakoff Syndrome

The aim of this study was to objectively evaluate the hypothesis that the neuropsychological presentation of Korsakoff’s syndrome, the chronic phase of Wernicke–Korsakoff syndrome (WKS), is invariably a severe, selective amnesia against a background of relatively preserved general intellectual functions in a consecutive clinical sample. An analysis of the neuropsychological profiles of nine cases with a recorded history of WKS was undertaken. All cases were adult males (ages 32 to 70) with a long history of alcohol use disorder. Eight cases were chosen retrospectively on a consecutive basis from patient referrals. One additional case was recruited prospectively. Conventional understanding and some current opinion of Korsakoff’s syndrome predicts anterograde memory to be consistently more impaired than other cognitive abilities, but this was not found in this case series. The Mean Wechsler Delayed Memory Index was not significantly different from the Wechsler Full-Scale IQ (FSIQ), p = 0.130. Regression of Delayed Memory on FSIQ produced a non-significant intercept, p = 0.213. The ‘hallmark’ criterion of anterograde memory score at least 20 points less than intelligence score was observed in four of eight cases with available data, equating to a ‘sensitivity’ of 50%. Three of eight cases with available data had an FSIQ less than the memory score. Contrary to a common view, general intellectual function was not consistently preserved in Korsakoff’s syndrome relative to memory function. This study illustrates one of the specific merits of case series, namely, to critique an established view. Clinicians and researchers should expand their diagnostic criteria for Korsakoff’s syndrome to include more variable cognitive phenotypes, including a potentially reversible dementia-like impairment of variable severity, and focus on potential treatment opportunities.

Impaired Executive Functioning Associated with Alcohol-Related Neurocognitive Disorder including Korsakoff's Syndrome.

(1) Background: chronic alcohol use is consistently associated with impaired executive functioning, but its profile across the spectrum from mild to major alcohol-related cognitive impairment is, to date, unclear. This study aims to compare executive performances of patients with alcohol-induced neurocognitive disorder, including Korsakoff's syndrome (KS), by using a computerized assessment battery allowing a fine-grained and precise neuropsychological assessment; (2) Methods: performances of 22 patients with alcohol-related cognitive impairment (ARCI) and 20 patients with KS were compared to those of 22 matched non-alcoholic controls. All participants were diagnosed in accordance with DSM-5-TR criteria and were at least six weeks abstinent from alcohol prior to assessment. Executive function was evaluated using four subtests of Cambridge Neuropsychological Test Automated Battery (CANTAB®); (3) Results: significant differences between groups were found on spatial working memory (updating), sustained attention and inhibitory control, set shifting, and planning. Healthy controls performed significantly better than both patient groups (Games-Howell post hoc; p < 0.05), but no differences in performance were found between the ARCI and KS group; (4) Conclusions: ARCI and KS patients showed significant executive impairments, most prominent in updating, set-shifting and general planning abilities. Findings suggest equivalent levels of executive function in ARCI and KS patients. Our results highlight executive function as a significant hallmark of alcohol-induced neurocognitive disorder and stipulate the importance of early assessment and evaluation of skills to guide treatment.

The importance of thiamine (vitamin B1) in humans.

Thiamine (thiamin, B1) is a vitamin necessary for proper cell function. It exists in a free form as a thiamine, or as a mono-, di- or triphosphate. Thiamine plays a special role in the body as a coenzyme necessary for the metabolism of carbohydrates, fats and proteins. In addition, it participates in the cellular respiration and oxidation of fatty acids: in malnourished people, high doses of glucose result in acute thiamine deficiency. It also participates in energy production in the mitochondria and protein synthesis. In addition, it is also needed to ensure the proper functioning of the central and peripheral nervous system, where it is involved in neurotransmitter synthesis. Its deficiency leads to mitochondrial dysfunction, lactate and pyruvate accumulation, and consequently to focal thalamic degeneration, manifested as Wernicke's encephalopathy or Wernicke-Korsakoff syndrome. It can also lead to severe or even fatal neurologic and cardiovascular complications, including heart failure, neuropathy leading to ataxia and paralysis, confusion, or delirium. The most common risk factor for thiamine deficiency is alcohol abuse. This paper presents current knowledge of the biological functions of thiamine, its antioxidant properties, and the effects of its deficiency in the body.

A - 89 Cognitive Evaluation of Suspected Wernicke- Korsakoff's Encephalopathy in a Woman with Complicated Hyperemesis Gravidarum.

Wernicke-Korsakoff syndrome (WKS) is a neurological disorder caused by the lack of thiamine (vitamin B1) and includes Wernicke encephalopathy and the later stage of Korsakoff amnesic syndrome. WKS could be secondary to malnutrition, including Hyperemesis Gravidarum (HEG), which is characterized by severe vomiting during pregnancy. We present a case of HEG resulting in suspected WKS where neuropsychological evaluation clarified cognitive status with complex cultural, language, and educational factors. Repeat evaluations of a 29-year-old West-African* woman with mental status change, decreased verbal output, agitation, and inability to walk in the context of HEG. Initially referred for inpatient neuropsychological evaluation at 21weeks gestation. MRI demonstrated mild diffuse cerebral atrophy and symmetric foci of T2 FLAIR hyperintensities in periaqueductal gray matter, hypothalamus, bilateral thalami, perirolandic cortex, and bilateral mammillary bodies. Initial inpatient testing with a face-to-face language congruent interpreter demonstrated notable multidomain impairment. Possible Intellectual Disability was considered by the referring team and test performances. Attempts at re-evaluation were limited by medical complications and prolonged hospitalization. Repeat inpatient evaluation 5months later following birth of healthy child and initiation of stimulant medication, demonstrated profound memory impairment but otherwise improved cognitive capacity and engagement. Results aided in discharge planning including cognitive remediation with goal of improving functional independence. Wernicke-Korsakoff syndrome due to Hyperemesis Gravidarum is an uncommon but known complication that can have profound acute and long-term consequences. This case demonstrates that repeat neuropsychological evaluations can clarify cognitive status in complex medical/cultural/language situations. *(country of origin and primary language not provided for patient privacy).