Impaired Global Precedence Effect in Severe Alcohol Use Disorder and Korsakoff's Syndrome: A Pilot Exploration through a Global/Local Visual Paradigm.

In healthy populations, visual abilities are characterized by a faster and more efficient processing of global features in a stimulus compared to local ones. This phenomenon is known as the global precedence effect (GPE), which is demonstrated by (1) a global advantage, resulting in faster response times for global features than local features and (2) interference from global distractors during the identification of local targets, but not vice versa. This GPE is essential for adapting visual processing in everyday life (e.g., extracting useful information from complex scenes). We investigated how the GPE is affected in patients with Korsakoff's syndrome (KS) compared to patients with severe alcohol use disorder (sAUD). Three groups (including healthy controls, patients with KS and patients with sAUD) completed a global/local visual task in which predefined targets appeared at the global or local level during either congruent or incongruent (i.e., interference) situations. The results showed that healthy controls (N = 41) presented a classical GPE, while patients with sAUD (N = 16) presented neither a global advantage nor global interference effects. Patients with KS (N = 7) presented no global advantage and an inversion of the interference effect, characterized by strong interference from local information during global processing. The absence of the GPE in sAUD and the interference from local information in KS have implications in daily-life situations, providing preliminary data for a better understanding of how these patients perceive their visual world.

Distinct Sleep Alterations in Alcohol Use Disorder Patients with and without Korsakoff's Syndrome: Relationship with Episodic Memory.

Alcohol Use Disorder (AUD) results in sleep disturbances that may have deleterious impacts on cognition, especially on memory. However, little is known about the sleep architecture in patients with Korsakoff's syndrome (KS). This study aims at characterizing sleep disturbances in KS compared to AUD without KS and at specifying the relationships with cognitive impairments. Twenty-nine AUD patients (22 without KS and 7 with KS) and 15 healthy controls underwent a neuropsychological assessment and a polysomnography. The severity of sleep-disordered breathing and sleep fragmentation was similar in AUD and KS patients compared to controls. Sleep architecture differed between both patient groups: the proportion of slow-wave sleep was reduced in AUD patients only, while a lower proportion of rapid-eye movement (REM) sleep was specifically observed in KS patients. The proportion of REM sleep correlated with the severity of episodic memory deficits when AUD and KS were examined together. These data provide evidence for both similarities and specificities regarding sleep alterations in AUD patients with and without KS. They also indicate that altered sleep architecture may contribute to the pathophysiology of alcohol-related memory disorders.

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.

Trimethylamine N-Oxide (TMAO) and Indoxyl Sulfate Concentrations in Patients with Alcohol Use Disorder.

BACKGROUND: Trimethylamine N-oxide (TMAO) and indoxyl sulfate (IS) are produced by the microbiota and the liver, and can contribute to brain aging and impaired cognitive function. This study aims to examine serum TMAO and IS concentrations in patients with alcohol-use disorder (AUD) at the entry for alcohol withdrawal, and the relationships with several biological, neuropsychological, and clinical parameters. METHODS: TMAO and IS were quantified in thirty AUD inpatients and fifteen healthy controls (HC). The severities of AUD and alcohol withdrawal syndrome (AWS), and general cognitive abilities were assessed in AUD patients. RESULTS: TMAO concentrations did not differ between HC and AUD patients. Several biomarkers assessing nutritional status and liver function were significantly different in AUD patients with the lowest TMAO concentrations compared to other AUD patients. IS concentration was significantly lower in AUD patients and a significant positive predictor of serum prealbumin variation during the acute phase of alcohol withdrawal. No relationship was observed between the concentrations of these metabolites and the severities of alcohol dependence, AWS, or cognitive deficits. CONCLUSIONS: Our data suggest that AUD patients with low concentrations of TMAO or IS should probably benefit from a personalized refeeding program during the acute phase of alcohol withdrawal.

Alcohol Withdrawal Is an Oxidative Stress Challenge for the Brain: Does It Pave the Way toward Severe Alcohol-Related Cognitive Impairment?

Alcohol use is a leading cause of mortality, brain morbidity, neurological complications and minor to major neurocognitive disorders. Alcohol-related neurocognitive disorders are consecutive to the direct effect of chronic and excessive alcohol use, but not only. Indeed, patients with severe alcohol use disorders (AUD) associated with pharmacological dependence suffer from repetitive events of alcohol withdrawal (AW). If those AW are not managed by adequate medical and pharmacological treatment, they may evolve into severe AW, or be complicated by epileptic seizure or delirium tremens (DT). In addition, we suggest that AW favors the occurrence of Wernicke's encephalopathy (WE) in patients with known or unknown thiamine depletion. We reviewed the literature on oxidative stress as a core mechanism in brain suffering linked with those conditions: AW, epileptic seizure, DT and WE. Thus, we propose perspectives to further develop research projects aiming at better identifying oxidative stress brain damage related to AW, assessing the effect of repetitive episodes of AW, and their long-term cognitive consequences. This research field should develop neuroprotective strategies during AW itself or during the periwithdrawal period. This could contribute to the prevention of severe alcohol-related brain damage and cognitive impairments.

Prognostic factors for low-risk drinking and relapse in alcohol use disorder: A multimodal analysis.

This study aims to specify the determinants of low-risk alcohol drinking and relapse at different time points after detoxification in patients with severe alcohol use disorder (AUD). Fifty-four patients with AUD and 36 healthy controls (HC) were evaluated early in abstinence (T1). They underwent clinical, neuropsychological and neuroimaging (structural MRI and 18 FDG-PET) investigations. Patients with AUD were subsequently classified as "low-risk drinkers" (LR) or "relapsers" (R) based on their alcohol drinking at 6 months (T2) and 1 year (T3) after discharge, using their medical record or self-reported drinking estimation at follow-up. Based on the alcohol status at T2 and compared with HC, only R had alexithymia, lower grey matter volume in the midbrain and hypermetabolism in the cerebellum and hippocampi. Based on the alcohol status at T3 and compared with HC, only R had more severe nicotinic dependence, lower episodic and working memory performance, lower grey matter volume in the amygdala, ventromedial prefrontal cortex and anterior cingulate gyrus and hypermetabolism in cerebellum, hippocampi and anterior cingulate gyrus. Moreover, R had bilateral frontal hypometabolism, whereas LR only presented right frontal hypometabolism. Nicotine dependence, memory impairments and structural brain abnormalities in regions involved in impulsivity and decision-making might contribute to a 1-year relapse. Treatment outcome at 1 year may also be associated with an imbalance between a hypermetabolism of the limbic system and a hypometabolism of the frontal executive system. Finally, cerebellar hypermetabolism and alexithymia may be determinants of relapse at both 6 months and 1 year.

Determinants of health-related quality of life in recently detoxified patients with severe alcohol use disorder.

BACKGROUND: Health-related quality of life (HRQoL) is an important clinical outcome in Alcohol Use Disorder (AUD) and is considered as a relevant indicator of treatment success. While a better understanding of the factors affecting HRQoL would enable to adjust patients' care to favour treatment outcome, the determinants of HRQoL in AUD remain unclear. This study aims at describing HRQoL in AUD patients and at identifying its best predictors. METHODS: 53 recently detoxified patients with severe AUD (sAUD) underwent a cognitive assessment and filled in a HRQoL questionnaire dedicated to AUD patients (Alcohol Quality of Life Scale; AQoLS), as well as questionnaires concerning socio-demographics, alcohol history, sleep quality, depression, anxiety and impulsivity. 38 healthy controls (HC) underwent the same assessment (except AQoLS) in order to identify the altered cognitive and clinical variables that could potentially be determinants of HRQoL in sAUD. RESULTS: sAUD patients reported that alcohol affects their HRQoL mainly in the "negative emotions", "control", "relationships", and "sleep" domains. Compared to HC, they were impaired on episodic memory, working memory, executive functions, and processing speed tasks. They also reported lower sleep quality, higher depression, anxiety and impulsivity. No association was found between AQoLS total score and socio-demographics, cognitive performance, or sleep quality in patients. We found a significant correlation between HRQoL and depression/anxiety as well as impulsivity. Anxiety and impulsivity were indeed the only significant predictors of HRQoL, explaining 47.7% of the variance. CONCLUSION: Anxiety and impulsivity are crucial determinants of HRQoL in recently detoxified sAUD patients. Since anxiety and impulsivity are frequent issues in addiction and especially in AUD, they should be particularly considered by clinicians to favour treatment outcomes.

Temporal Cognitive and Brain Changes in Korsakoff Syndrome.

OBJECTIVE: To investigate cognitive and brain changes in patients with Korsakoff syndrome (KS) over months and up to 10 years after the diagnosis. METHODS: Two groups of 8 patients with KS underwent neuropsychological, motor, and neuroimaging investigations, including structural MRI and 18F-fluorodeoxyglucose-PET. The KSC group, recruited at Caen University Hospital, was examined early after the KS diagnosis (KSC-T1) and 1 year later (KSC-T2). The KSR group, recruited at nursing home at Roubaix, was evaluated 10 years after the diagnosis. Longitudinal comparisons in KSC explored short-term changes, while cross-sectional comparisons between KSC-T1 and KSR informed about long-term changes. RESULTS: No cognitive, motor, or brain deterioration occurred over time in patients with KS. There was no clear improvement either, with only modest recovery in the frontocerebellar circuit. Compared to the norms, KSC-T1 had severe episodic memory impairments, ataxia, and some executive dysfunctions. They also presented widespread atrophy and hypometabolism as well as cerebellar hypermetabolism compared to 44 healthy matched controls. Episodic memory remained significantly impaired in KSC-T2 and KSR. Contrary to KSC at T1 and T2, KSR had preserved inhibition abilities. Atrophy was similar but less extended in KSC-T2 and even more limited in KSR. At all times, the thalamus, hypothalamus, and fornix remained severely atrophied. Hypometabolism was still widespread in KSC-T2 and KSR, notably affecting the diencephalon. Cerebellar metabolism decreased over time and normalized in KSR, whereas motor dysfunction persisted. CONCLUSION: In KS, structural and metabolic alterations of the Papez circuit persisted over time, in accordance with the irreversible nature of amnesia. There was neither significant recovery as observed in patients with alcohol use disorder nor progressive decline as in neurodegenerative diseases.

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.

Thiamine and phosphate esters concentrations in whole blood and serum of patients with alcohol use disorder: a relation with cognitive deficits.

Background: In this study, we investigated (1) the effect of chronic and excessive alcohol consumption on whole blood (WB) and serum concentrations of thiamine and its metabolites after supplementation, and (2) the relationship between the perturbations of thiamine metabolism and neuropsychological abilities.Methods: WB and serum samples were collected in patients with Alcohol Use Disorder (AUD) and in healthy control subjects (after oral thiamine supplementation, or without supplementation). Thiamine (Th), thiamine monophosphate (TMP) and thiamine diphosphate (TDP) were quantified. The Brief Evaluation of Alcohol-Related Neuropsychological Impairments (BEARNI) and the Montreal Cognitive Assessment (MoCA) were performed by each AUD participant. Based on the BEARNI score, two groups of AUD patients were studied: AUD patients with no or mild cognitive impairment (AUD COG+), and AUD patients with moderate-to-severe cognitive impairment (AUD COG-).Results: In WB, Th concentrations were significantly higher, and percentages of phosphate esters of thiamine were significantly lower in AUD COG- patients compared to controls. In serum, Th concentrations were significantly higher in AUD COG- patients compared to controls. The percentage of Th in serum was significantly higher in AUD COG- patients compared to AUD COG+ patients, and to the groups of controls. When adjusted on education level, the percentage of Th in serum in AUD patients negatively correlated with the scores at BEARNI and MoCA, and Th concentration in serum negatively correlated with MoCA.Conclusions: These data support an impairment of metabolism and/or distribution of thiamine in AUD patients, and a relationship with the development of alcohol-related cognitive deficits.

Short-term neuropsychological recovery in alcohol use disorder: A retrospective clinical study.

BACKGROUND: Neuropsychological impairments found in recently detoxified patients with alcohol use disorder (AUD) can limit the benefit of psychosocial treatments and increase the risk of relapse. These neuropsychological deficits are reversible with abstinence. The aim of this retrospective clinical study was to investigate whether a short-term stay as inpatients in a convalescent home enables neuropsychological deficits observed in recently detoxified AUD patients to recover and even performance to return to normal. METHODS: Neuropsychological data were collected in 84 AUD patients. Five neuropsychological components were assessed before and after a three-week stay in a convalescent home offering multidisciplinary support. Baseline and follow-up performance were compared in the entire group of patients and in subgroups defined by the nature and intensity of the therapy (OCCASIONAL: occasional occupational and physical therapy; INTENSIVE: intensive occupational and physical therapy and neuropsychological training). RESULTS: In the entire group of patients, neuropsychological performance significantly improved between baseline and follow-up for all 5 components and even returned to a normal level for 4 of them. The ratio of patients with impaired performance was significantly lower at follow-up than baseline examination for 3 components in the INTENSIVE group only. CONCLUSION: Recently detoxified AUD patients with cognitive deficits benefit from a short-term stay in an environment ensuring sobriety and healthy nutrition. Cognitive recovery may be enhanced by intensive care including neuropsychological training. Alcohol programs could be postponed in patients with cognitive deficits in order to offer psychosocial treatment when patients are cognitively able to benefit from it.

The effect of alcohol withdrawal syndrome severity on sleep, brain and cognition.

In alcohol use disorder, drinking cessation is frequently associated with an alcohol withdrawal syndrome. Early in abstinence (within the first 2 months after drinking cessation), when patients do not exhibit physical signs of alcohol withdrawal syndrome anymore (such as nausea, tremor or anxiety), studies report various brain, sleep and cognitive alterations, highly heterogeneous from one patient to another. While the acute neurotoxicity of alcohol withdrawal syndrome is well-known, its contribution to structural brain alterations, sleep disturbances and neuropsychological deficits observed early in abstinence has never been investigated and is addressed in this study. We included 54 alcohol use disorder patients early in abstinence (from 4 to 21 days of sobriety) and 50 healthy controls. When acute physical signs of alcohol withdrawal syndrome were no longer present, patients performed a detailed neuropsychological assessment, a T1-weighted MRI and a polysomnography for a subgroup of patients. According to the severity of the clinical symptoms collected during the acute withdrawal period, patients were subsequently classified as mild alcohol withdrawal syndrome (mild-AWS) patients (Cushman score ≤ 4, no benzodiazepine prescription, N = 17) or moderate alcohol withdrawal syndrome (moderate-AWS) patients (Cushman score > 4, benzodiazepine prescription, N = 37). Patients with severe withdrawal complications (delirium tremens or seizures) were not included. Mild-AWS patients presented similar grey matter volume and sleep quality as healthy controls, but lower processing speed and episodic memory performance. Compared to healthy controls, moderate-AWS patients presented non-rapid eye movement sleep alterations, widespread grey matter shrinkage and lower performance for all the cognitive domains assessed (processing speed, short-term memory, executive functions and episodic memory). Moderate-AWS patients presented a lower percentage of slow-wave sleep, grey matter atrophy in fronto-insular and thalamus/hypothalamus regions, and lower short-term memory and executive performance than mild-AWS patients. Mediation analyses revealed both direct and indirect (via fronto-insular and thalamus/hypothalamus atrophy) relationships between poor sleep quality and cognitive performance. Alcohol withdrawal syndrome severity, which reflects neurotoxic hyperglutamatergic activity, should be considered as a critical factor for the development of non-rapid eye movement sleep alterations, fronto-insular atrophy and executive impairments in recently detoxified alcohol use disorder patients. The glutamatergic activity is involved in sleep-wake circuits and may thus contribute to molecular mechanisms underlying alcohol-related brain damage, resulting in cognitive deficits. Alcohol withdrawal syndrome severity and sleep quality deserve special attention for a better understanding and treatment of brain and cognitive alterations observed early in abstinence, and ultimately for more efficient relapse prevention strategies.

Cerebellar Hypermetabolism in Alcohol Use Disorder: Compensatory Mechanism or Maladaptive Plasticity?

BACKGROUND: Despite severe structural brain abnormalities within the frontocerebellar circuit (FCC), cerebellar metabolism studied with 18 F-2-fluoro-deoxy-glucose-positron emission tomography (FDG-PET) is relatively preserved in patients with alcohol use disorder (AUD). The compensatory role of the cerebellum has been explored mainly through fMRI examination of AUD patients with the preserved level of performance. The present study aims at examining cerebellar metabolism and its relationship with regional brain metabolism and neuropsychological functioning in AUD patients. METHODS: Thirty-two recently detoxified AUD patients and 23 controls underwent an FDG-PET examination at rest. Participants also performed a neuropsychological battery assessing executive functions, verbal memory, and ataxia. RESULTS: Compared to controls, AUD patients had higher glucose uptake in the cerebellar lobule VIII, in association with hypometabolism, notably in several nodes of the FCC. Cerebellar hypermetabolism correlated negatively with regional hypometabolism in the premotor and frontal cortices. This pattern of regional hypermetabolism and hypometabolism related to ataxia and working memory deficits. CONCLUSIONS: These specific brain-behavior relationships do not fulfill the criteria for brain compensatory processes. Cerebellar hypermetabolism may rather reflect the involvement of different pathological mechanisms, leading to a maladaptive plasticity phenomenon within the FCC in AUD patients who are early in abstinence. Further studies are required to examine the contributions of structural and functional connectivity alterations in the cerebellar hypermetabolism and the changes in these pathological mechanisms with abstinence or relapse.

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.

Neuropsychological and Neuroimaging Examinations of Self-Reported Sleep Quality in Alcohol Use Disorder With and Without Korsakoff's Syndrome.

BACKGROUND: Alcohol use disorder (AUD) patients without Korsakoff's syndrome (KS) report a variable self-rated sleep quality. Their ability to accurately judge their sleep quality may be related to their alcohol-related cognitive deficits and brain damage. KS patients, who present severe brain dysfunction, may be cognitively unable to judge their sleep quality. The aim of the present study is to examine, in AUD and KS patients, whether the absence of sleep complaint is associated with altered brain structure and impaired cognitive abilities within specific cerebral networks. METHODS: An assessment of subjective sleep quality was conducted in 20 healthy controls, 37 AUD patients, and 17 KS patients. Patients were first pooled together and then classified into 2 groups (no-complaintAUD + KS and complaintAUD + KS ) according to the total Pittsburg Sleep Quality Index score. Cognitive scores, gray matter (GM) volume, and white matter (WM) integrity were compared between these 2 groups, and then in AUD and KS patients separately. RESULTS: Poor sleep quality was reported by 70% of AUD and 18% of KS patients. Compared to controls, both no-complaintAUD + KS and complaintAUD + KS presented cortical and subcortical alterations as well as episodic memory deficits, which were more severe in patients without sleep complaint. Only no-complaintAUD + KS presented executive deficits. Then, considering the clinical diagnosis, GM volume in frontotemporal regions, WM integrity, and executive functions were affected to the same extent in AUD and KS patients without sleep complaint. CONCLUSIONS: Our results confirm the high prevalence of sleep complaint in AUD patients and the rare complaint in KS patients. In AUD and KS patients, the absence of sleep complaint may not indicate good sleep quality but rather reflect executive deficits and frontothalamic damage. Alcohol-related cognitive deficits may indeed alter the ability to self-evaluate sleep quality, suggesting that the use of sleep questionnaire should be considered with caution in patients with executive deficits.

[Alcohol induced neurocognitive disorder: screening strategies and tools]. / Repérage des troubles cognitifs liés à l'alcool.

Alcohol induced neurocognitive disorder: screening strategies and tools. Chronic and excessive alcohol consumption results in cognitive disorders partially reversible with abstinence. These heterogeneous cognitive impairments affect executive functions, episodic memory and social cognition. They may interfere with the motivational process to abandon excessive drinking behavior, impair patients' ability to benefit from treatment and increase the risk of relapse. Alcohol-related neuropsychological deficits should thus be evaluated and considered for personalized alcohol treatment. Several screening tools available in clinical settings enable clinicians to detect patients with cognitive impairments and to offer them appropriate and adjusted treatment.

Repérage des troubles cognitifs liés à l'alcool. La consommation chronique et excessive d'alcool est fréquemment associée à des troubles cognitifs, en partie réversibles à l'arrêt de l'alcool. Variables d'un individu à l'autre, ils touchent principalement les fonctions exécutives et motrices, la mémoire épisodique, ainsi que la cognition sociale. Ces troubles peuvent freiner le processus motivationnel, amoindrir les capacités des patients à bénéficier des prises en charge et augmenter le risque de rechute. Plusieurs outils de dépistage rapide sont disponibles en pratique clinique. Ils permettent d'orienter les patients ayant une altération cognitive vers des prises en charge spécialisées pour la réalisation de bilans complémentaires. Le profil neuropsychologique des patients peut aussi éclairer les difficultés de prise en charge et permettre de personnaliser les soins addictologiques.

[Cognitive impairment]. / Atteintes cognitives liées au trouble de l'usage d'alcool : rétablir l'équilibre ?

Alcohol use disorder is a brain disease that can be modeled by an imbalance between three cerebral and cognitive systems. The reflective system, underpinned by the frontal cortex and corresponding to the executive functions, would be involved in the control of alcohol consumption. The impulsive system, underpinned by the amygdala-striatal complex, would favor automatic and impulsive drinking behaviors. A regulatory system, driven by insula and involved in the integration of proprioceptive perceptions in situations of deprivation or stress, would aggravate the imbalance between the two first systems. This model provides a new framework for understanding alcohol use disorder and new perspectives on therapeutic targets that could be included into integrated and customized treatments.

Clinical and Biological Risk Factors for Neuropsychological Impairment in Alcohol Use Disorder.

The effects of alcoholism on cognitive and motor functioning are heterogeneous. While the role of some factors (patterns of alcohol consumption, eating habits or associated liver disease) has been hypothesized, the origins of this heterogeneity remain difficult to establish. The goals of the present study were thus to identify the clinical and biological risk factors for alcohol-related neuropsychological impairments and to determine the threshold beyond which these risk factors can be considered significant. Thirty alcoholic patients and 15 healthy controls had a blood test and underwent a neuropsychological examination. Alcohol severity measures, and liver, thiamine and malnutrition variables, were included in logistic regression models to determine the risk factors for cognitive and motor impairments (executive functions, visuospatial abilities, verbal episodic memory, ataxia), as well as those related to the severity of patients' overall neuropsychological profile (moderate or severe impairments). Liver fibrosis was found to be a risk factor for executive impairments and also for ataxia, when it was associated with long-term alcohol misuse and symptoms of withdrawal. Altered thiamine metabolism was solely predictive of verbal episodic memory impairments. This combination of biological abnormalities was associated with a profile of moderate neuropsychological impairments. Malnutrition was associated with a profile of more severe impairments. Malnutrition, altered liver function and thiamine metabolism explain, at least partially, the heterogeneity of alcohol-related neuropsychological impairments. Our findings could allow clinicians to identify patients at particular risk of severe neuropsychological impairments before the onset of irreversible and debilitating neurological complications.

[Alcohol-related neuropsychological impairments: Nature, impact and detection]. / Troubles cognitifs liés à l'alcool : nature, impact et dépistage.

Alcohol-related neuropsychological deficits result from chronic and excessive alcohol consumption and are associated with structural and functional damage of Papez's circuit and frontocerebellar circuit. Alcohol-related cognitive deficits are heterogeneous but especially affect executive functions and memory abilities. They result in difficulties to change alcohol behavior combined with a tendency for patients to overestimate their capacity to succeed. Alcohol-related cognitive deficits could be a risk-factor for relapse since they hamper patients to benefit fully from treatment (especially when based on relapse prevention). Screening tools usable by non-psychologists are available and can be completed by an extensive neuropsychological examination conducted by a neuropsychologist when necessary. Alcohol treatment should be adjusted to take alcohol-related cognitive deficits into account, by promoting longer treatment in healthy environment for example. Improvements of alcohol treatment options, including specific neuropsychological rehabilitation, are required for patients with persistent alcohol-related cognitive deficits.

Direct voxel-based comparisons between grey matter shrinkage and glucose hypometabolism in chronic alcoholism.

Alcoholism is associated with widespread brain structural abnormalities affecting mainly the frontocerebellar and the Papez's circuits. Brain glucose metabolism has received limited attention, and few studies used regions of interest approach and showed reduced global brain metabolism predominantly in the frontal and parietal lobes. Even though these studies have examined the relationship between grey matter shrinkage and hypometabolism, none has performed a direct voxel-by-voxel comparison between the degrees of structural and metabolic abnormalities. Seventeen alcoholic patients and 16 control subjects underwent both structural magnetic resonance imaging and (18)F-2-fluoro-deoxy-glucose-positron emission tomography examinations. Structural abnormalities and hypometabolism were examined in alcoholic patients compared with control subjects using two-sample t-tests. Then, these two patterns of brain damage were directly compared with a paired t-test. Compared to controls, alcoholic patients had grey matter shrinkage and hypometabolism in the fronto-cerebellar circuit and several nodes of Papez's circuit. The direct comparison revealed greater shrinkage than hypometabolism in the cerebellum, cingulate cortex, thalamus and hippocampus and parahippocampal gyrus. Conversely, hypometabolism was more severe than shrinkage in the dorsolateral, premotor and parietal cortices. The distinct profiles of abnormalities found within the Papez's circuit, the fronto-cerebellar circuit and the parietal gyrus in chronic alcoholism suggest the involvement of different pathological mechanisms.