Search

International audience; Aims: To specify the determinants of low-risk alcohol drinking and relapse at different timepoints after detoxification in patients with severe Alcohol Use Disorder (AUD).Methods: Fifty-four AUD patients and 36 healthy controls (HC) were evaluated early inabstinence (T1). They underwent clinical, neuropsychological and neuroimaging (structuralMRI and 18FDG-PET) investigations.AUD patients were subsequently classified as “low-risk drinkers” (LR) or “relapsers” (R)based on their alcohol drinking at 6 months (T2) and one year (T3) after discharge, using theirmedical record or self-reported drinking estimation at follow-up.Results: Based on the alcohol status at T2 and compared to HC, only R had alexithymia,lower gray matter volume in the midbrain and hypermetabolism in the cerebellum andhippocampi. Based on the alcohol status at T3 and compared to HC, only R had more severenicotinic dependence, lower episodic and working memory performance, lower gray mattervolume in the amygdala, ventromedial prefrontal cortex and anterior cingulate gyrus, andhypermetabolism in cerebellum, hippocampi and anterior cingulate gyrus. Moreover, R hadbilateral frontal hypometabolism, whereas LR only presented right frontal hypometabolism.Conclusion: Nicotine dependence, memory impairments, and structural brain abnormalitiesin regions involved in impulsivity and decision-making might contribute to a one-yearrelapse. Treatment outcome at one year may also be associated with an imbalance between ahypermetabolism of the limbic system and a hypometabolism of the frontal executive system.Finally, cerebellar hypermetabolism and alexithymia may be determinants of relapse at both 6months and one year.

International audience; Cognitive and brain alterations are common in alcohol use disorder and vary importantly from one patient to another. Sleep disturbances are also very frequent in these patients and remain largely neglected even though they can persist after drinking cessation. Sleep disturbances may be the consequence of specific brain alterations, resulting in cognitive impairments. But sleep disruption may also exacerbate alcohol-related brain abnormalities and cognitive deficits through common pathophysiological mechanisms. Besides, sleep disturbances seem a vulnerability factor for the development of alcohol use disorder. From a clinical perspective, sleep disturbances are known to affect treatment outcome and to increase the risk of relapse. In this article, we conducted a narrative review to provide a better understanding of the relationships between sleep disturbances, brain and cognition in alcohol use disorder. We suggest that the heterogeneity of brain and cognitive alterations observed in patients with alcohol use disorder could at least partially be explained by associated sleep disturbances. We also believe that sleep disruption could indirectly favor relapse by exacerbating neuropsychological impairments required in psychosocial treatment and for the maintenance of abstinence. Implications for clinical practice as well as perspectives for future research are proposed.

ObjectiveTo investigate cognitive and brain changes in patients with Korsakoff syndrome (KS) over months and up to 10 years after the diagnosis.MethodsTwo 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.ResultsNo 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.ConclusionIn 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.

Points cles Le trouble de l’usage d’alcool est une maladie du cerveau resultant d’un desequilibre entre trois systemes cerebraux et cognitifs. Un premier systeme, dit reflexif, sous-tendu par le cortex frontal et correspondant aux fonctions executives et jouerait un role de controle des consommations d’alcool. Un second systeme, dit impulsif, sous-tendu par le complexe amygdalo-striatal, favorisait les comportements automatiques et impulsifs de consommation d’alcool. Un systeme regulateur, sous-tendu par l’insula et implique dans l’integration des perceptions proprioceptives dans des contextes de privation ou de stress, viendrait aggraver le desequilibre entre les deux premiers systemes. Ce modele offre une nouvelle grille de lecture du trouble de l’usage d’alcool et de nouvelles perspectives de cibles therapeutiques qui pourraient s’inscrire dans des programmes de soins integres et personnalises.

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 supplementa...

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.

Alcohol-related cognitive impairments are largely underestimated in clinical practice, even though they could limit the benefit of alcohol treatment and hamper the patient's ability to remain abstinent or to respect his/her therapeutic contract. These neuropsychological deficits can impact the management of patients well before the development of the well-known Korsakoff's syndrome. Indeed, even in the absence of ostensible neurological complications, excessive and chronic alcohol consumption results in damage of brain structure and function. The frontocerebellar circuit and the circuit of Papez, respectively involved in motor and executive abilities and episodic memory, are mainly affected. Those brain dysfunctions are associated with neuropsychological deficits, including deficits of executive functions, episodic memory, social cognition, as well as visuospatial and motor abilities. Such cognitive disorders can interfere with the motivation process to abandon maladjusted drinking behavior in favor of a healthier lifestyle (such as abstinence or controlled alcohol consumption). They can also limit the patient's capacity to fully benefit from treatment (notably psychoeducation and cognitive-behavioural treatments) currently widely proposed in French Addiction departments. In addition, they may contribute to relapse which is multi-determinated. A neuropsychological assessment appears therefore crucial to take relevant clinical decisions. However, very few addiction departments have the human and financial resources to conduct an extensive neuropsychological examination of all patients with alcohol dependence. Some brief screening tools can be used, notably the MOntreal Cognitive Assessment and the Brief Evaluation of Alcohol-Related Neuropsychological Impairments, which has been especially designed to assess cognitive and motor deficits in alcoholism. These tools can be used by non-psychologist clinicians to detect alcohol-related cognitive deficits, which require an extensive cognitive examination conducted by a neuropsychologist. The presence of cognitive dysfunctions in patients early in abstinence should encourage clinicians to adjust the modalities of the treatment. The fact to favor recovery of cognitive functions and brain volumes with abstinence or drastic reduction of alcohol consumption could be a first way to make it possible for patients to be cognitively able to benefit from treatment. Further studies are required to determine whether specifically designed cognitive remediation could boost (accelerate or increase) the recovery of brain functioning. Additionally, a potential effect of thiamine to limit alcohol-related cognitive deficits before the development of neurological complications remains to be determined. In this review, we presented the pattern of structural brain damage and the associated cognitive and motor impairments in alcohol-dependent patients. We then emphasized the harmful effects of neuropsychological deficits in the management of these patients. We also pointed how relevant it is to screen patients with neuropsychological impairments and we focused on the presentation of two brief screening tools for cognitive impairments, especially designed for alcohol-related deficits or not. Finally, we reported how these neuropsychological impairments could be taken into consideration the treatment of alcohol addiction by adjusting its timing and modalities.

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.

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 18F-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.

Les troubles du sommeil et l’alcoolo-dépendance (AD) sont deux comorbidités fréquemment associées dans les pathologies psychiatriques, telles que l’anxiété, la dépression, les troubles bipolaires ou la schizophrénie [1]. Depuis plusieurs années, les études conduites dans l’AD ont permis de mieux préciser les atteintes cognitives et cérébrales de ces patients [2]. Par ailleurs, certains résultats ont également souligné chez les AD la présence d’altérations du sommeil (36 à 72 % selon les études) qui seraient un facteur de risque de rechute [3]. En pratique clinique, l’évaluation du sommeil est principalement réalisée à l’aide de questionnaires, du fait de leur rapidité de passation et leur facilité d’analyse. L’objectif de cette étude est d’explorer les liens entre la plainte du sommeil évaluée à l’aide d’un autoquestionnaire nommé le « Pittsburg Sleep Quality Index » (PSQI) [4], les troubles cognitifs et les altérations cérébrales structurales des patients AD. Trente-neuf patients AD et 16 sujets sains recrutés au sein du protocole ALCOBRAIN ont été inclus dans la présente étude. Nos données indiquent que plus de 76 % des patients AD abstinents évoquent une plainte de sommeil. Les patients qui ne rapportent pas de plainte de sommeil présentent les troubles exécutifs les plus sévères. Par ailleurs, ces patients présenteraient également des altérations cérébrales plus importantes que ceux présentant une plainte de sommeil, notamment au sein de régions impliquées dans les capacités de métacognition. Ces résultats suggèrent qu’une forme infraclinique d’anosognosie pourrait être présente chez certains patients AD, entraînant une conscience partielle de leurs troubles du sommeil. En pratique clinique, il semble donc nécessaire de rester vigilant vis-à-vis de l’évaluation subjective du sommeil par le biais de questionnaires. Des études complémentaires sont nécessaires afin de préciser les liens entre sommeil, cognition et cerveau, notamment à l’aide de mesures objectives de la qualité du sommeil.

Background: It is still unclear whether episodic memory and executive functions capacities can return to normal in abstinent patients over a 6-month period. Furthermore, the role of interim drinking in cognitive recovery is still not well known. Finally, further research is required to specify the predictive value of cognitive abilities at initial testing in the treatment outcome (abstinence or relapse). The aims of the present study were therefore to measure changes in episodic memory and executive functions over a 6-month period in abstinent and relapsed alcoholics and to ascertain whether neuropsychological results at treatment entry can predict treatment outcome at follow-up. Methods: Fifty-four alcoholic patients and 54 matched control subjects performed baseline neuropsychological tasks assessing episodic memory, executive functions, the slave systems of working memory and attentional abilities. At the follow-up session (i.e., 6 months later), episodic memory and 3 executive functions (inhibition, flexibility, and updating) were re-examined in the alcoholic patients. Results: Results showed that over the 6-month interval, the abstainers’ episodic memory and executive performances had returned to normal, whereas the relapsers performed lower than before in the flexibility task. Episodic memory and executive functions recovery was correlated, in abstainers, with drinking history and age respectively. Finally, there was no significant difference regarding neuropsychological scores at baseline between abstainers and relapsers. Discussion: Over the 6-month interval, abstainers normalized episodic memory and executive performances whereas relapsers obtained executive results which were more severely impaired, emphasizing the influence of interim drinking on cognitive changes. Episodic memory, executive functions, the slave systems of working memory and attentional abilities did not appear to be reliable predictors of treatment outcome over a 6-month interval.

Background Chronic alcohol consumption results in brain damage potentially reversible with abstinence. It is however difficult to gauge the degree of recovery of brain tissues with abstinence since changes are subtle and a significant portion of patients relapse. State-of-the-art morphometric methods are increasingly used in neuroimaging studies to detect subtle brain changes at a voxel level. Our aim was to use the most refined morphometric methods to observe in alcohol dependence the relationship between volumetric changes and interim drinking over a 6-month follow-up. Methods Overall, 19 patients with alcohol dependence received volumetric T1-weighted magnetic resonance imaging (MRI) after detoxification. A 6-month follow-up study was then conducted, during which 11 of them received a second MRI scan. First, correlations were conducted between gray matter (GM) and white matter (WM) volumes of patients at alcohol treatment entry and the amount of alcohol consumed between treatment entry and follow-up. Second, longitudinal analyses were performed from pairs of MRI scans using tensor-based morphometry in the 11 patients, and correlations were computed between the resultant Jacobian maps of GM and WM and interim drinking. Results Our preliminary results showed that, among others, alcoholics with smaller thalamus at alcohol treatment entry tended to resume with heavy alcohol consumption (p

High motivation to change is a crucial triggering factor to patients' engagement in clinical treatment. This study investigates whether the low readiness to change observed in some alcoholic inpatients at treatment entry could, at least partially, be linked with macrostructural gray matter abnormalities in critical brain regions. Participants comprised 31 alcoholic patients and 27 controls, who underwent 1.5-T magnetic resonance imaging. The Readiness to Change Questionnaire, designed to assess three stages of motivation to change (precontemplation, contemplation and action stages), was completed by all patients, who were then divided into "Action" (i.e., patients in action stage) and "PreAction" (i.e., patients in precontemplation or in contemplation stage) subgroups. The PreAction subgroup, but not the Action subgroup, had gray matter volume deficits compared with controls. Unlike the patients in the Action subgroup, the PreAction patients had gray matter abnormalities in the cerebellum (Crus I), fusiform gyri and frontal cortex. The low level of motivation to modify drinking behavior observed in some alcoholic patients at treatment entry may be related to macrostructural brain abnormalities in regions subtending cognitive, emotional and social abilities. These brain volume deficits may result in impairment of critical abilities such as decision making, executive functions and social cognition skills. Those abilities may be needed to resolve ambivalence toward alcohol addiction and to apply "processes of change", which are essential for activating the desire to change problematic behavior.

Background While procedures acquired before the development of amnesia are likely to be preserved in alcoholic patients with Korsakoff's syndrome, the ability of Korsakoff patients (KS) to learn new cognitive procedures is called in question. According to the Adaptive Control of Thoughts model, learning a new cognitive procedure requires highly controlled processes in the initial cognitive phase, which may be difficult for KS with episodic and working memory deficits. The goals of the present study were to examine the learning dynamics of KS compared with uncomplicated alcoholic patients (AL) and control subjects (CS) and to determine the contribution of episodic and working memory abilities in cognitive procedural learning performance. Methods Fourteen KS, 15 AL, and 15 CS were submitted to 40 trials (4 daily learning sessions) of the Tower of Toronto task (disk-transfer task similar to the tower of Hanoi task) as well as episodic and working memory tasks. Results The 10 KS who were able to perform the cognitive procedural learning task obtained lower results than both CS and AL. The cognitive phase was longer in the Korsakoff's syndrome group than in the other 2 groups but did not differ between the 3 groups any more when episodic memory abilities were controlled. Conclusions Our results indicate that KS have impaired cognitive procedural learning abilities compared with both AL and CS. Episodic memory deficits observed in KS result in a delayed transition from the cognitive learning phase to more advanced learning phases and, as a consequence, in an absence of automation of the procedure within 40 trials.

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

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