Criminal behavior in alcohol-related dementia and Wernicke-Korsakoff syndrome: a Nationwide Register Study.

BACKGROUND: Chronic heavy alcohol use may lead to permanent brain damage, cognitive impairment, and dementia. While the link between alcohol use and crime is strong, virtually no research exists on the criminal behavior of patients with the alcohol-related neurocognitive disorders of Wernicke-Korsakoff syndrome (WKS) and alcohol-related dementia (ARD). METHODS: The study population included all persons diagnosed with WKS (n = 1149) or ARD (n = 2432) in Finland in 1998-2015. Data on diagnoses, mortality, and crime were obtained from Finnish nationwide registers. Crime incidences were calculated 4 years before and after diagnosis. Crime types, incidences, and mortality were compared between disorders and with the general population. RESULTS: Altogether 35.6% of WKS patients and 23.6% of ARD patients had committed crimes in the 4 years preceding diagnosis, most commonly property and traffic crimes, followed by violent crimes. The incidence of criminal behavior decreased significantly after diagnosis; in WKS patients, the standardized criminality ratio (SCR), the ratio of observed to expected number of crimes (95% CI), was 3.91 (3.72-4.10) in 4 years before and 2.80 (2.61-3.00) in 4 years after diagnosis. Likewise, in ARD patients, the SCRs were 2.63 (2.51-2.75) before and 0.84 (0.75-0.92) after diagnosis. No significant difference emerged in mortality between persons with and without a criminal history. CONCLUSIONS: Persons with alcohol-related neurocognitive disorders frequently engage in criminal behavior prior to diagnosis, especially multiple offending. In the 4 years before and after diagnosis, crime rates declined in a linear fashion, with a marked reduction after diagnosis.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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.

Structural brain substrates of the deficits observed on the BEARNI test in alcohol use disorder and Korsakoff's syndrome.

Chronic and excessive alcohol consumption can result in alcohol use disorder (AUD) without neurological complications and in Korsakoff's syndrome (KS) when combined with thiamine deficiency. These two clinical forms are accompanied by widespread structural brain damage in both the fronto-cerebellar (FCC) and Papez circuits (PC) as well as in the parietal cortex, resulting in cognitive and motor deficits. BEARNI is a screening tool especially designed to detect neuropsychological impairments in AUD. However, the sensitivity of this tool to the structural brain damage of AUD and KS patients remains unknown. Eighteen KS patients, 47 AUD patients and 27 healthy controls (HC) underwent the BEARNI test and a 3 T-MRI examination. Multiple regression analyses conducted between GM density and performance on each BEARNI subtest revealed correlations with regions included in the FCC, PC, thalamus and posterior cortex (precuneus and calcarine regions). All these brain regions were altered in KS compared to HC, in agreement with the cognitive deficits observed in the corresponding BEARNI subtests. The comparison between KS and AUD regarding the GM density in the several nodes of the FCC and calcarine regions revealed that they were atrophied to the same extent, suggesting that BEARNI is sensitive to the severity of alcohol-related GM abnormalities. Within the PC, the density of the cingulate cortex and thalamus, which correlated with the memory and fluency subscores, was smaller in KS than in AUD, suggesting that BEARNI is sensitive to specific brain abnormalities occurring in KS.

The era of our lives: The memory of Korsakoff patients for the first Covid-19 pandemic lockdown in the Netherlands.

Memories for worldwide and emotional events (such as 9/11) are more vividly relived and recalled than memories for everyday events. Previous studies have shown that flashbulb memories of a single event enhanced the memory strength in severe amnesia. It is currently unknown whether macro-events that stretch out over longer periods of time (weeks, months) strengthen memory even further. Our aim was therefore to investigate to what extent patients with severe amnesia, due to Korsakoff's syndrome (KS), were able to relive the first Covid-19 lockdown in the Netherlands, and whether experienced emotions enhanced reliving of the participants. We included 22 KS patients and 24 age-, education-, and gender-matched healthy controls. Covid-19 related memories were assessed by measures of autobiographical memory specificity, phenomenological reliving, emotional intensity and semantic-and episodic knowledge about the first lockdown in March 2020 - May 2020 in the Netherlands. Although amnesia patients remembered significantly fewer autobiographical details regarding the Covid-19 lockdown than healthy controls, one fourth of the KS patients recalled specific events. Amnesia patients reported levels of emotional intensity equivalent to those in the control group. Stronger autobiographical reliving was associated with higher emotional intensity. Both amnesia patients and healthy controls had higher recall of episodic than semantic lockdown related information. In conclusion, results demonstrate that information for macro-events can still be memorized and relived, most specifically when emotional valence is high, even by highly amnestic patients.

"Ten dollars today or 50 dollars after one month?" Temporal discounting in Korsakoff syndrome.

OBJECTIVE: Little research has investigated decision making in patients with Korsakoff syndrome (KS). Specifically, to our knowledge, there is a lack of research investigating whether patients with KS may tend to prefer immediate over future rewards (i.e., temporal discounting). Further, we investigated the relationship between temporal discounting and inhibition. METHODS: We, for the first time, invited patients with KS and control participants to perform a temporal discounting task, in which they answered questions probing preferences between an immediate, but smaller amount of money, and a delayed, but larger amount of money (e.g., "would you prefer 10 dollars today or 50 dollars after one month?"). Furthermore, inhibition was measured using the Stroop Colour Word Test. RESULTS: Analysis demonstrated higher temporal discounting in patients with KS than in control participants. Temporal discounting in both populations was significantly correlated with inhibition. CONCLUSIONS: Patients with KS may have difficulties to suppress the temptation of smaller, but immediate, rewards.

"Cinderella was attacked by the big bad wolf, but the police saved her": intrusions and confabulations on story recall in Korsakoff's syndrome and alcohol-related cognitive impairments.

BACKGROUND: The relation between confabulations and intrusions in patients with Korsakoff's syndrome (KS) and patients with alcohol-related cognitive impairments (ARCI) remains under debate. This study examines (1) differences in the production of confabulations and intrusions between patients with KS and ARCI, (2) whether an altered fairy tale induces more intrusions, and (3) whether different types of intrusions were significantly related to confabulations. METHODS: Twenty-three patients with KS and twenty-two patients with ARCI recalled three different types of stories: a novel story, a fairy tale, and a modified fairy tale. Different types of intrusions were correlated with confabulation measures. RESULTS: Patients with KS produced more intrusions in the modified fairy tale condition than patients with ARCI, but these were unrelated to confabulations. Only unrelated intrusions were related to provoked confabulations. CONCLUSIONS: The results of this study indicate that researchers and clinicians must be aware that in general, intrusions on memory tests should not be interpreted as confabulations. Especially spontaneous confabulations appear to be something completely different from intrusions on any type of story recall. When measuring confabulations it is crucial to use validated instruments.

What is the optimum thiamine dose to treat or prevent Wernicke's encephalopathy or Wernicke-Korsakoff syndrome? Results of a randomized controlled trial.

BACKGROUND: The primary cause of Wernicke-Korsakoff syndrome (WKS) is thiamine deficiency, and more than 90% of cases are reported in alcohol-dependent patients. While observational studies show parenteral thiamine administration drastically reduced WKS-related mortality, relevant treatment trials have never been conducted to determine the optimum thiamine dose. METHODS: Two double-blind, parallel groups, randomized controlled trials (RCTs) were conducted to determine the optimal thiamine dose required for (1) the prevention of Wernicke's encephalopathy (WE), the acute phase of WKS, in asymptomatic but "at-risk" alcohol misuse patients (Study 1) and (2) the treatment of WE in symptomatic alcohol misuse patients (Study 2). Each study had a dosage regimen comprising three parenteral thiamine doses that were allocated at a ratio of 1:1:1. Study 1: Asymptomatic At-Risk patients (N = 393) received either 100 mg daily, 100 mg thrice daily, or 300 mg thrice daily, for 3 days. Study 2: Symptomatic patients (N = 127) received either 100 mg thrice daily, 300 mg thrice daily, or 500 mg thrice daily, for 5 days. Cognitive function was the primary outcome, assessed using the Rowland Universal Dementia Assessment Scale, two Cogstate subtests, and an adapted Story Memory Recall test. Secondary analyses examined differences in neurological function (ataxia, oculomotor abnormalities, and confusion) at follow-up. RESULTS: No significant differences were observed between any of the dosage conditions for either Study 1 or Study 2 on cognition or neurological functioning. This real-world study found that having a clinically unwell target population with high comorbidity and multiple presentations, coupled with challenges in cross-cultural assessment is likely to complicate RCT findings. CONCLUSIONS: The results of this study showed no clear benefit of high dose thiamine over intermediate or lower doses of thiamine, over the time intervals examined, for the treatment and prevention of cognitive and neurological abnormalities related to WKS. Several study limitations temper the interpretation of these findings. Nevertheless, the absence of conclusive evidence for the superiority of high-dose thiamine supports a recommendation for patient-specific treatment, while ensuring that the potential impact of other biochemical factors (e.g., magnesium and other B vitamin deficiencies) are considered and corrected if necessary.

Bromisoval-induced bromism with status epilepticus mimicking Wernicke's encephalopathy: report of two cases.

BACKGROUND: Bromine compounds are used in several drugs, including over-the-counter drugs. They sometimes cause intoxication known as bromism. Although the acute neurological symptoms and sequelae of bromism vary, few reports have mentioned acute encephalopathy. CASE PRESENTATION: We report two cases of bromisoval-induced bromism with status epilepticus. Presence of pseudohyperchloremia and history of over-the-counter medication use guided the diagnosis. In the acute phase, our patients showed bilateral medial thalamic lesions on magnetic resonance imaging. The imaging findings were similar to those of Wernicke's encephalopathy. Although these findings improved in the chronic phase, neuropsychiatric sequelae, such as confabulation and amnesia, occurred. CONCLUSION: Bromism can cause acute encephalopathy, and it is important to differentiate it from Wernicke-Korsakoff syndrome.

Smartwatch reminders are as effective as verbal reminders in patients with Korsakoff's syndrome: three case studies.

Korsakoff's syndrome (KS) is a neurocognitive disorder caused by severe malnutrition. KS patients typically show severe impairments in prospective memory (PM), thus, have difficulties with remembering to perform delayed intentions. The current study investigated the possible benefits of a smartwatch aid for PM tasks in patients with KS and compared its efficacy with verbal in-person reminders. Three patients participated in the present study and were asked to complete everyday PM tasks. The results of each patient were analyzed as a single-case study. The results highlight the great potential of using smartwatches as external memory aids in KS patients in everyday life.

Incidence and mortality of alcohol-related dementia and Wernicke-Korsakoff syndrome: A nationwide register study.

BACKGROUND: Epidemiological data on alcohol-related cognitive disorders are scarce. Up-to-date population-based incidence and mortality rates for Wernicke-Korsakoff syndrome (WKS) and alcohol-related dementia (ARD) are necessary to understand the burden of these diseases. METHODS: We collected diagnostic data from the Finnish Hospital Discharge Register and mortality data from Statistics Finland for all persons aged ≥40 years who had received a diagnosis of WKS (n = 1149) or ARD (n = 2432) between 1998 and 2015 in Finland. We calculated the incidences and mortality in relation to the age-, sex- and calendar year-matched general population. Causes of death were ascertained from death certificates. RESULTS: For WKS, the incidence per 100,000 person-years (95% confidence interval (CI)) was 3.7 (3.4-3.9) in men and 1.2 (1.1-1.3) in women. For ARD, the incidence was 8.2 (7.9-8.6) in men and 2.1 (1.9-2.3) in women. The incidence of WKS peaked in people aged 50-59 years and the incidence of ARD in people aged 70-79 years. The standardized mortality ratio (95% CI) was 5.67 (5.25-6.13) in WKS patients and 5.41 (5.14-5.70) in ARD patients. Most of the excess mortality resulted from alcohol-related causes. CONCLUSIONS: To our knowledge, this is the first study describing population-based incidence and mortality rates, sex-segregated data and causes of death in patients with WKS or ARD. Our results establish a point of reference for the incidence of WKS and ARD and show the high mortality and poor prognosis of these disorders.

Behavioural effects of light intervention in people with Korsakoff Syndrome: A pilot study.

Korsakoff Syndrome (KS) is commonly associated with behavioural symptoms such as agitation, apathy, and disinhibition. People with KS often reside in long-term care facilities, which reduces their exposure to natural light. Little is known regarding positive effects of light intervention in KS. Our objective was to evaluate the influence of a dawn simulation therapy on behavioural symptoms in KS. 38 patients residing in a 24-hour care facility were exposed for 6 weeks to a dawn simulation system in their bedrooms, which gradually increased from 0 lux to 290 lux. Behavioural symptoms were measured over 9 weeks. Weeks 1-3 consisted of the baseline phase and weeks 3-9 consisted of the light intervention phase. Our study showed that total severity of neuropsychiatric symptoms was less prominent during light intervention. More specifically, a decrease on the apathy, disinhibition, behaviour at night and appetite and eating behaviour subscales was found during the light intervention phase compared to the baseline phase. Additionally, a significant effect was found on decreasing emotional distress for caregivers. Results suggest that light intervention therapy has a positive effect on reducing behavioural symptoms in KS as well as the levels of stress experienced by the patients' caregivers.

Gayet-Wernicke Syndrome: The eye surgeon in a French neurologic eponym.

Gayet-Wernicke syndrome is an eponym mainly used in France. In this article, we revisit Charles Gayet's (1833-1904) speciality and his patient example that gave rise to the eponym. Charles Gayet attributed the anatomical lesions to inflammation. However, they were mainly due to hemorrhage, as Wernicke's term "polioencéphalite supérieure aiguë hémorragique" (polio-encephalitis superior haemorrhagica) explicitly indicates. The pathology of Gayet's case did not involve the mamillary bodies, colliculi, or cerebellum. Gayet did not mention abnormal memory functions, which are also cardinal signs of Wernicke-Korsakoff's disease. We argue that the Gayet-Wernicke eponym is not merited and that the more common international term "Wernicke-Korsakoff syndrome" should be used in France as elsewhere in the world.

Confabulations in post-acute and chronic alcoholic Korsakoff's syndrome: a cross-sectional study conducted in two centres.

INTRODUCTION: Confabulations refer to the emergence of memories of experiences and events that are incorrect in place and time, or never took place. In alcoholic Korsakoff's syndrome, confabulations have been frequently reported, but seldomly been investigated. Traditional reports on confabulations state that confabulations in KS mainly occur in the post-acute phase of the illness. The aim of the study was to investigate whether confabulations extinguish in KS. METHODS: An observational rating of confabulation behaviour (the NVCL-R) was completed for 172 KS patients with alcoholic KS. Post-acute and chronic KS patients were compared cross-sectionally in two centres. RESULTS: Provoked and spontaneous confabulations were present in post-acute and chronic patients. Patients residing in a long-term care facility more often presented themselves with spontaneous confabulations than patients in a diagnostic centre. CONCLUSIONS: In contrast to the traditional view, confabulations may be present throughout the course of KS, and are possibly more frequently present in patients receiving care in specialised long-term care facilities than in patients who receive less intensive support.Key pointsConfabulations are a central characteristic of Korsakoff's syndromeIn contrast to popular belief, confabulations may be present in acute and chronic Korsakoff's syndromeThe severity of confabulations is related to an unfavourable disease outcome in KSA longitudinal approach would help the confirmation of finding no decline in confabulations over time.

Early Identification of Alcohol Use Disorder Patients at Risk of Developing Korsakoff's Syndrome.

BACKGROUND: The aim of the present study was to determine whether the Brief Evaluation of Alcohol-Related Neuropsychological Impairments (BEARNI), a screening tool developed to identify neuropsychological deficits in alcohol use disorder (AUD) patients, can also be used for the early identification of AUD patients at risk of developing Korsakoff's syndrome (KS). METHODS: Eighteen KS patients, 47 AUD patients and 27 healthy controls underwent BEARNI testing (including 5 subtests targeting episodic memory, working memory, executive function, visuospatial abilities, and ataxia) and a comprehensive neuropsychological examination. RESULTS: Performance of AUD and KS patients on BEARNI subtests was consistent with the results on the standardized neuropsychological assessment. On BEARNI, ataxia and working memory deficits observed in AUD were as severe as those exhibited by KS patients, whereas for visuospatial abilities, a graded effect of performance was found. In contrast, the subtests involving long-term memory abilities (episodic memory and fluency) were impaired in KS patients only. AUD patients with a score lower than 1.5 points (out of 6) on the episodic memory subtest of BEARNI exhibited the lowest episodic memory performance on the neuropsychological battery and could be considered at risk of developing KS. CONCLUSIONS: These findings suggest that BEARNI is a useful tool for detecting severe memory impairments, suggesting that it could be used for the early identification of AUD patients at high risk of developing KS.

Unraveling Apathy in Korsakoff Syndrome Patients Receiving Long-Term Care With and Without Cerebrovascular Comorbidity.

BACKGROUND: Korsakoff syndrome (KS) is a severe neuropsychiatric disorder caused by acute deficiency of vitamin B1 and concomitant alcoholism. Patients with KS are particularly vulnerable for cerebrovascular comorbidity. KS is characterized by cognitive and neuropsychiatric symptoms, one of which is apathy. Apathy is a pathological lack of goal-directed behaviors, goal-directed cognitions, and goal-directed emotions. Cerebrovascular accidents are known to carry a risk for developing apathy. Apathy has a dramatic effect on the autonomy and daily lives of patients suffering from this condition. METHODS: We assessed general apathy and related subconstructs in fifteen patients with KS, fifteen patients with KS and cerebrovascular comorbidity who reside in a 24-hour care facility, and fifteen healthy controls. RESULTS: Compared with healthy controls, both KS patient groups showed higher levels of apathy as rated by a close informant. We found no difference between both KS patient groups and the healthy control group on the self-report section of the Pleasant Activities List, suggesting that motivation is still intact in KS patients. It is important to note a discrepancy was found between self-reporting and proxy reporting on this list. KS patients with cerebrovascular comorbidity showed more severe emotional blunting compared to both KS patients without cerebrovascular comorbidity and healthy controls. The competency to consent was lower in patients compared with healthy controls, but no difference was found between KS patients with cerebrovascular comorbidity and those without. CONCLUSIONS: Our results suggest that KS patients show increased levels of general apathy compared with healthy controls. Patients show a diminished competency to consent and increased emotional blunting, while motivation is not compromised. Cerebrovascular comorbidity in KS forms a high risk for emotional blunting. The results of this study suggest that apathy is a severe problem in KS. More attention in both the literature and clinical practice would benefit this complex patient population.

High emotional experience during autobiographical retrieval in women with Korsakoff syndrome.

INTRODUCTION: In this exploratory study, we investigated gender differences regarding autobiographical memory in KS. METHOD: We invited 33 patients with KS and 35 matched control participants to retrieve autobiographical memories and, afterward, to rate mental time travel during retrieval, emotional value and importance of memories. RESULTS: Analysis demonstrated lower specificity (i.e., lower ability to retrieve memories situated in a specific time and space), mental time travel, and importance in patients with KS compared to control participants. Analysis also demonstrated no significant difference between patients with KS and control participants regarding emotion. Critically, analysis demonstrated no significant differences neither women and men with KS, nor between women and men in the control group, regarding autobiographical specificity, mental time travel, or importance. However, women with KS attributed higher emotional value for memories compared to men with KS, and the same results were observed in the control group. DISCUSSION: These findings demonstrate that the higher emotional experience during autobiographical retrieval, as observed in the general population, can also be observed in KS.

Caregivers' perspectives on good care for nursing home residents with Korsakoff syndrome.

BACKGROUND: In the Netherlands, people with severe cognitive deficits due to Korsakoff syndrome are generally admitted to a specialized nursing home. Professional caregivers experience that these residents are often not aware of their deficits, and consequently, their willingness to accept care is relatively low. However, these residents need permanent support when performing daily tasks due to severe cognitive deficits. The combination of objective care needs and low subjective responsiveness makes caring for people with Korsakoff syndrome a complex undertaking. It is unknown how professional caregivers deal with this complex task and how they manage the associated ethical challenges. OBJECTIVES: The aim of this study was to explore the professional caregivers' perspectives on good care for residents with Korsakoff syndrome. METHODS: A qualitative study design was used. Data were collected via semi-structured interviews. The Framework Method was used for the thematic analyses of the interview data. PARTICIPANTS AND RESEARCH CONTEXT: Five specialized nursing homes participated in this study. Twelve professional caregivers, including nurses, nursing assistants, and support workers, were selected based on the ability to provide rich information on the study topics and to capture a variety of demographic and professional characteristics. ETHICAL CONSIDERATIONS: The institutional review board of the VU University Medical Center Amsterdam approved the research protocol. The study was conducted in accordance with the ethical principles for medical research involving human subjects. FINDINGS: Three perspectives on good care emerged: (1) making daily life a joint effort, (2) being steadfast, and (3) treating with respect. DISCUSSION AND CONCLUSION: Professional caregivers try to achieve responsiveness in people with Korsakoff syndrome in three different ways. These perspectives reflect fundamentally different views on the care relationship and the autonomy of the resident. By elucidating the three perspectives, we hope to promote the practitioners' reflection on their own ideas about good care for people with Korsakoff syndrome.

Autobiographical memory in Korsakoff syndrome: A review.

Autobiographical memory (AM) (i.e., memory for personal information) is a unique form of memory that goes beyond recalling information such as what, where and when of an event, to include what that event means and why it is important to our life story. This paper therefore reviews the available literature on AM in Korsakoff syndrome (KS). It summarizes the characteristics of AM disorders in KS patients. These disorders are mainly characterized by the difficulties that patients with KS have in retrieving and reliving specific AMs and in retrieving recent and remote memories. Another core characteristic of AM disorders in KS is confabulations. This paper hypothesizes that patients with KS may produce autobiographical confabulations to support their objectives and beliefs or even to answer a social demand or simply to share personal experiences with others. Although the current evidence demonstrates disorders of AM in KS, there is a need for more research about the characteristics of these disorders. This review thus proposes several perspectives for theoretical and clinical research.

Brain 18FDG-PET pattern in patients with alcohol-related cognitive impairment.

PURPOSE: Brain positron emission tomography using 18F-fluorodeoxyglucose (18FDG-PET) provides a metabolic assessment of brain function that is useful for differential diagnosis among several neurodegenerative diseases manifested by cognitive impairment (CI). The purpose of the study is to describe the pattern of 18FDG-PET abnormalities in patients with CI related to alcohol use disorder. METHODS: Patients admitted to the addiction medicine department of a university hospital in Paris between January 2017 and October 2018 with a confirmed diagnosis of alcohol-related cognitive impairment (ARCI) or Wernicke encephalopathy (WE) were included. Brain 18FDG-PET uptake was measured after at least 1 month of monitored abstinence from alcohol. Standardized uptake values were obtained for 13 regions of interest (ROI) and normalized to the pons. Individual patients' ROI Z-scores were calculated from healthy sex- and age-matched controls provided by Cortex ID software. RESULTS: Twenty-five patients were included in the analysis (20 males and 5 females; mean age 57.6 years (45-76 years old)). The group consisted of 19 ARCI and 6 WE cases. The mean hypometabolism was most severe in the prefrontal medial cortex (PFM) (- 2.80 (± 1.30)), the prefrontal lateral cortex (- 2.20 (± 1.35)), and the anterior cingulate cortex (- 2.24 (± 1.19)). Hypometabolism (Z-score < - 2) was most frequent in the PFM (72.0% of the sample, N = 18). Other regions were also affected (with 5.32/13 hypometabolic ROIs on average (SD = 4.16, range 0-13)). The Z-scores in the 13 ROIs did not differ significantly between the ARCI and WE patients (p ≥ 0.05). CONCLUSIONS: Predominant prefrontal and cingulate cortex hypometabolism was the most frequent brain 18FDG-PET pattern in our sample of patients with ARCI and WE.

Dissociating thalamic alterations in alcohol use disorder defines specificity of Korsakoff's syndrome.

The thalamus, a relay organ consisting of several nuclei, is shared between the frontocerebellar circuit and the Papez circuit, both particularly affected in alcohol use disorder. Shrinkage of the thalamus is known to be more severe in alcoholics with Korsakoff's syndrome than in those without neurological complications (uncomplicated alcoholics). While thalamic atrophy could thus be a key factor explaining amnesia in Korsakoff's syndrome, the loci and nature of alterations within the thalamic nuclei in uncomplicated alcoholics and alcoholics with Korsakoff's syndrome remains unclear. Indeed, the literature from animal and human models is disparate regarding whether the anterior thalamic nuclei, or the mediodorsal nuclei are particularly affected and would be responsible for amnesia. Sixty-two participants (20 healthy controls, 26 uncomplicated alcoholics and 16 patients with Korsakoff's syndrome) underwent a diffusion tensor imaging sequence and T1-weighted MRI. State-of-the-art probabilistic tractography was used to segment the thalamus according to its connections to the prefrontal cortex and cerebellar Cruses I and II for the frontocerebellar circuit's executive loop, the precentral gyrus and cerebellar lobes IV-VI for the frontocerebellar circuit's motor loop, and hippocampus for the Papez circuit. The connectivity and volumes of these parcellations were calculated. Tractography showed that the hippocampus was principally connected to the anterior thalamic nuclei while the prefrontal cortex was principally connected to the mediodorsal nuclei. The fibre pathways connecting these brain regions and their respective thalamic nuclei have also been validated. ANCOVA, with age and gender as covariates, on connectivity measures showed abnormalities in both patient groups for thalamic parcellations connected to the hippocampus only [F(2,57) = 12.1; P < 0.0001; η2 = 0.2964; with graded effects of the number of connections from controls to uncomplicated alcoholics to Korsakoff's syndrome]. Atrophy, on the other hand, was observed for the prefrontal parcellation in both patient groups and to the same extent compared to controls [F(2,56) = 18.7; P < 0.0001; η2 = 0.40]. For the hippocampus parcellation, atrophy was found in the Korsakoff's syndrome group only [F(2,56) = 5.5; P = 0.006; η2 = 0.170, corrected for multiple comparisons using Bonferroni, P < 0.01]. Post hoc Tukey's test for unequal sample sizes, healthy controls > patients with Korsakoff's syndrome (P = 0.0036). Two different mechanisms seem to affect the thalamus. In the frontocerebellar circuit, atrophy of the mediodorsal nuclei may lead to the alterations, whereas in the Papez circuit, disconnection between the anterior nuclei and hippocampus may be the leading factor. Shrinkage of the anterior nuclei could be specific to patients with Korsakoff's syndrome, hence a potential neuroimaging marker of its pathophysiology, or more generally of thalamic amnesia for which Korsakoff's syndrome has historically been used as a model.