Effects of sleep disturbances and circadian rhythms modifications on cognition in breast cancer women before and after adjuvant chemotherapy: the ICANSLEEP-1 protocol.

BACKGROUND: Many patients treated for breast cancer (BC) complain about cognitive difficulties affecting their daily lives. Recently, sleep disturbances and circadian rhythm disruptions have been brought to the fore as potential contributors to cognitive difficulties in patients with BC. Yet, studies on these factors as well as their neural correlates are scarce. The purpose of the ICANSLEEP-1 (Impact of SLEEP disturbances in CANcer) study is to characterize sleep using polysomnography and its relationship with the evolution of cognitive functioning at both the behavioral and the neuroanatomical levels across treatment in BC patients treated or not with adjuvant chemotherapy. METHODS: ICANSLEEP-1 is a longitudinal study including BC patients treated with adjuvant chemotherapy (n = 25) or not treated with adjuvant chemotherapy (n = 25) and healthy controls with no history of BC (n = 25) matched for age (45-65 years old) and education level. The evaluations will take place within 6 weeks after inclusion, before the initiation of chemotherapy (for BC patients who are candidates for chemotherapy) or before the first fraction of radiotherapy (for BC patients with no indication for chemotherapy) and 6 months later (corresponding to 2 weeks after the end of chemotherapy). Episodic memory, executive functions, psychological factors, and quality of life will be assessed with validated neuropsychological tests and self-questionnaires. Sleep quantity and quality will be assessed with polysomnography and circadian rhythms with both actigraphy and saliva cortisol. Grey and white matter volumes, as well as white matter microstructural integrity, will be compared across time between patients and controls and will serve to further investigate the relationship between sleep disturbances and cognitive decline. DISCUSSION: Our results will help patients and clinicians to better understand sleep disturbances in BC and their relationship with cognitive functioning across treatment. This will aid the identification of more appropriate sleep therapeutic approaches adapted to BC patients. Improving sleep in BC would eventually help limit cognitive deficits and thus improve quality of life during and after treatments. TRIAL REGISTRATION: NCT05414357, registered June 10, 2022. PROTOCOL VERSION: Version 1.2 dated March 23, 2022.

Insular volumetry in severe alcohol use disorder and Korsakoff's syndrome through an anatomical parcellation: Let us go back to basics.

Functional neuroimaging has demonstrated the key role played by the insula in severe alcohol use disorder (sAUD), notably through its involvement in craving and body signals processing. However, the anatomical counterpart of these functional modifications in sAUD patients with and without neurological complications remains largely unexplored, especially using state-of-the-art parcellation tools. We thus compared the grey matter volume of insular subregions (form anterior to posterior: anterior inferior cortex, anterior short gyrus, middle short gyrus, posterior short gyrus, anterior long gyrus, posterior long gyrus) in 50 recently detoxified patients with sAUD, 19 patients with Korsakoff's syndrome (KS) and 36 healthy controls (HC). We used a mixed linear model analysis to explore group differences in the six subregions grey matter volume and lateralization differences. Insular macrostructure was globally affected to the same extent in sAUD with and without KS, indicating that these brain abnormalities may be related to alcohol consumption per se, rather than to the presence of alcohol-related neurological complications. Insular atrophy showed a right-sided lateralization effect and was especially marked in the posterior insula, a region associated with visceral information processing and the embodiment effect of a substance, from which craving arises. Anatomical damages might thus underlie the previously reported altered insular activations and their behavioural counterparts.

Korsakoff's Syndrome and Alzheimer's Disease-Commonalities and Specificities of Volumetric Brain Alterations within Papez Circuit.

Background: Alzheimer's disease (AD) and Korsakoff's syndrome (KS) are two major neurocognitive disorders characterized by amnesia but AD is degenerative while KS is not. The objective is to compare regional volume deficits within the Papez circuit in AD and KS, considering AD progression. Methods: 18 KS patients, 40 AD patients (20 with Moderate AD (MAD) matched on global cognitive deficits with KS patients and 20 with Severe AD (SAD)), and 70 healthy controls underwent structural MRI. Volumes of the hippocampi, thalami, cingulate gyri, mammillary bodies (MB) and mammillothalamic tracts (MTT) were extracted. Results: For the cingulate gyri, and anterior thalamic nuclei, all patient groups were affected compared to controls but did not differ between each other. Smaller volumes were observed in all patient groups compared to controls in the mediodorsal thalamic nuclei and MB, but these regions were more severely damaged in KS than AD. MTT volumes were damaged in KS only. Hippocampi were affected in all patient groups but more severely in the SAD than in the KS and MAD. Conclusions: There are commonalities in the pattern of volume deficits in KS and AD within the Papez circuit with the anterior thalamic nuclei, cingulate cortex and hippocampus (in MAD only) being damaged to the same extent. The specificity of KS relies on the alteration of the MTT and the severity of the MB shrinkage. Further comparative studies including other imaging modalities and a neuropsychological assessment are required.

Disruption in normal correlational patterns of metabolic networks in the limbic circuit during transient global amnesia.

Transient global amnesia is characterized by the sudden apparition of severe episodic amnesia, mainly anterograde, associated with emotional changes. Even though the symptoms are stereotyped, cerebral mechanism underlying transient global amnesia remains unexplained and previous studies using positron emission tomography do not show any clear results or consensus on cerebral regions impacted during transient global amnesia. This study included a group of 10 transient global amnesic patients who underwent 18F-fluorodeoxyglucose positron emission tomography during the acute or recovery phase of the episode and 10 paired healthy controls. Episodic memory was evaluated with the encoding-storage-retrieval paradigm and a story recall test of the Wechsler's memory scale and anxiety was assessed with the Spielberger scale. We used statistical parametric mapping to identify modifications of whole-brain metabolism. Regarding hypometabolism, there was no brain region systematically affected in all transient global amnesic patients and the comparison between amnesic patients and controls did not show any significant differences. To better understand the specific implication of the limbic circuit in the pathophysiology of transient global amnesia, we then conducted a correlational analysis that included regions of this network. Our findings showed that in healthy controls, regions of the limbic circuit seem to operate in a synchronized way with all regions being highly correlated to each other. On the opposite, in transient global amnesic patients, we observed a clear disruption of this normal correlational patterns between regions with the medial temporal lobe (the hippocampus, parahippocampal gyrus and amygdala) included in one cluster and the orbitofrontal cortex, anterior and posterior cingulate gyrus and thalamus gathered in the other one. Given the individual variability in the time course of transient global amnesia, the direct comparison between a group of patients and controls does not seem to favour the identification of subtle and transient alterations in regional metabolism. The involvement of an extended network, such as the limbic circuit, seems more likely to explain the symptoms of patients. Indeed, the synchronization of regions within the limbic circuit seems to be altered during transient global amnesia, which could explain the amnesia and anxiety observed in transient global amnesic patients. The present study thus deepens our understanding of the mechanisms underlying not only amnesia but also the emotional component of transient global amnesia by considering it as a disruption in the normal correlational patterns within the limbic circuit.

Evaluation of the cognitive outcome after out-of-hospital cardiac arrest: The role of thalamus.

Cardiac arrest survivors develop a variety of neuropsychological impairments and neuroanatomical lesions. The goal of this study is to evaluate if brain voxel-based morphometry and lesional Magnetic Resonance Imaging (MRI) analyses performed in the acute phase of an Out-of-Hospital Cardiac Arrest (OHCA) can be sensitive enough to predict the persistence of neuropsychological disorders beyond 3 months. Survivors underwent a prospective brain MRI during the first month after an OHCA and performed neuropsychological assessments at 1 and 3 months. According to the second neuropsychological assessment, survivors were separated into two subgroups, a deficit subgroup with persistent memory, executive functions, attention and/or praxis disorders (n = 11) and a preserved subgroup, disorders free (n = 14). Brain vascular lesion images were investigated, and volumetric changes were compared with healthy controls. Correlations were discussed between brain MRI results, OHCA data and the second neuropsychological assessment. Analyses of acute ischemic lesions did not reveal significant differences between the two subgroups (p = .35), and correlations with cognitive impairments could not be assessed. voxel-based morphometry analyses revealed a global cerebral volume reduction for the two subgroups and a clear decrease of the right thalamic volume for the deficit subgroup. It was associated with a cognitive dysexecutive syndrome represented by four executive indexes according to the 'Groupe de Réflexion pour l'Evaluation des Fonctions EXécutives' criteria. The right thalamus atrophy seems to be more predictive than the vascular lesions and more specific than a global cerebral volume reduction of post-OHCA neuropsychological executive disorders.

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.

Rapid Eye Movement Sleep, Neurodegeneration, and Amyloid Deposition in Aging.

OBJECTIVE: Rapid eye movement (REM) sleep is markedly altered in Alzheimer's disease (AD), and its reduction in older populations is associated with AD risk. However, little is known about the underlying brain mechanisms. Our objective was to investigate the relationships between REM sleep integrity and amyloid deposition, gray matter volume, and perfusion in aging. METHODS: We included 121 cognitively unimpaired older adults (76 women, mean age 68.96 ± 3.82 years), who underwent a polysomnography, T1-weighted magnetic resonance imaging, early and late Florbetapir positron emission tomography scans to evaluate gray matter volume, perfusion, and amyloid deposition. We computed indices reflecting REM sleep macro- and microstructural integrity (ie, normalized electroencephalographic spectral power values). Voxel-wise multiple regression analyses were conducted between REM sleep indices and neuroimaging data, controlling for age, sex, education, the apnea-hypopnea index, and the apolipoprotein E ε4 status. RESULTS: Lower perfusion in frontal, anterior and posterior cingulate, and precuneus areas was associated with decreased delta power and electroencephalographic slowing (slow/fast frequencies ratio), and increased alpha and beta power. To a lower extent, similar results were obtained between gray matter volume and delta, alpha, and beta power. In addition, lower REM sleep theta power was more marginally associated with greater diffuse amyloid deposition and lower gray matter volume in fronto-temporal and parieto-occipital areas. INTERPRETATION: These results suggest that alterations of REM sleep microstructure are associated with greater neurodegeneration and neocortical amyloid deposition in older adults. Further studies are warranted to replicate these findings, and determine whether older adults exhibiting REM sleep alterations are more at risk of cognitive decline and belonging to the Alzheimer's continuum. ANN NEUROL 2023;93:979-990.

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.

Alterations in resting-state functional connectivity associated to the age-related decline in time-based prospective memory.

Time-based prospective memory (TBPM) is defined as the ability to remember to perform intended actions at a specific time in the future. TBPM is impaired in aging, and this decline has been associated with white-matter alterations within the superior fronto-occipital fasciculus. In the present study, we used resting-state functional magnetic resonance imaging from 22 healthy young (26 ± 5.2 years) and 23 older (63 ± 6.1 years) participants to investigate how age-related alterations in resting-state functional connectivity are related to TBPM performance, and whether these alterations are associated with the white-matter disruptions we have previously observed with diffusion tensor imaging. Whole-brain analyses revealed lower resting-state functional connectivity in older participants compared with younger ones, which in turn correlated with TBPM performance. These correlations were mainly located in the salience network and the parietal part of the frontoparietal network. Our findings suggest that resting-state functional connectivity alterations contribute to the age-related decline in TBPM.

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.

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.

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.

Longitudinal grey matter and metabolic contributions to cognitive changes in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis is characterized by rapidly evolving cognitive and brain impairments. While previous work revealed structural and functional alterations associated with cognitive decline in patients suffering from amyotrophic lateral sclerosis, the relationships between anatomo-functional changes and both disease's progression and the evolution of cognitive performance remain largely unexplored. Here, we took advantage of repeated multi-modal acquisitions in patients with amyotrophic lateral sclerosis over 1 year to assess the longitudinal sequence of grey matter atrophy, glucose metabolism and cognitive changes. Results revealed metabolic and structural changes over frontal, thalamic and temporal regions. Both cortical hypermetabolism and hypometabolism (right temporal gyrus and right angular gyrus, respectively) were associated with cognitive performance and thalamic hypometabolism during the follow-up testing session. Furthermore, the inferior frontal gyrus atrophy mediated the relation between early hypometabolism in this region and the subsequent decline of the theory of mind abilities. Marked volume loss was associated with larger hypometabolism and impaired cognitive performance. To our knowledge, this is the first study to longitudinally examine both grey matter volume and metabolic alteration patterns in patients with amyotrophic lateral sclerosis, over a mean follow-up time of 1 year. We identify how changes of the inferior frontal gyrus critically underly later cognitive performance, shedding new light on its high prognostic significance for amyotrophic lateral sclerosis-related changes. These results have important implications for our understanding of structural and functional changes associated with amyotrophic lateral sclerosis and how they underly cognitive impairments.

Role of inflammation in alcohol-related brain abnormalities: a translational study.

Brain abnormalities observed in alcohol use disorder are highly heterogeneous in nature and severity, possibly because chronic alcohol consumption also affects peripheral organs leading to comorbidities that can result in exacerbated brain alterations. Despite numerous studies focussing on the effects of alcohol on the brain or liver, few studies have simultaneously examined liver function and brain damage in alcohol use disorder, and even fewer investigated the relationship between them except in hepatic encephalopathy. And yet, liver dysfunction may be a risk factor for the development of alcohol-related neuropsychological deficits and brain damage well before the development of liver cirrhosis, and potentially through inflammatory responses. The use of animal models enables a better understanding of the pathophysiological mechanisms underlying liver-brain relationships in alcohol use disorder, and more particularly of the inflammatory response at the tissue, cerebral and hepatic levels. The objective of this translational study was to investigate, both in alcohol use disorder patients and in a validated animal model of alcohol use disorder, the links between peripheral inflammation, liver damage and brain alterations. To do this, we conducted an in vivo neuroimaging examination and biological measures to evaluate brain volumes, liver fibrosis and peripheral cytokines in alcohol use disorder patients. In selectively bred Sardinian alcohol-preferring rats, we carried out ex vivo neuroimaging examination and immunohistochemistry to evaluate brain and liver inflammatory responses after chronic (50 consecutive weeks) alcohol drinking. In recently abstinent and non-cirrhotic alcohol use disorder patients, the score of liver fibrosis positively correlated with subcortical regions volumes (especially in right and left putamen) and level of circulating proinflammatory cytokines. In Sardinian alcohol-preferring rats, we found macrostructural brain damage and microstructural white matter abnormalities similar to those found in alcohol use disorder patients. In addition, in agreement with the results of peripheral inflammation observed in the patients, we revealed, in Sardinian alcohol-preferring rats, inflammatory responses in the brain and liver were caused by chronic alcohol consumption. Since the liver is the main source of cytokines in the human body, these results suggest a relationship between liver dysfunction and brain damage in alcohol use disorder patients, even in the absence of major liver disease. These findings encourage considering new therapeutic strategies aiming at treating peripheral organs to limit alcohol-related brain damage.

The specificity of thalamic alterations in Korsakoff's syndrome: Implications for the study of amnesia.

The pathophysiological mechanisms behind amnesia are still unknown. Recent literature, through the study of patients with Alcohol Use Disorder with and without Korsakoff's syndrome, increasingly shows that physiological alterations to the thalamus have an important role in the development of amnesia. This review gives an overview of neuropsychological, neuropathological and neuroimaging contributions to the understanding of Korsakoff's syndrome, highlighting the central role of the thalamus in this amnesia. The thalamus being a multi-nucleus structure, the limitations regarding the loci, nature and alterations to specific nuclei are discussed, along with potential solutions. Finally, future directions for clinical research are laid out to unravel the intricacies inherent to amnesia. They consider the need to evaluate the physiological role of the thalamus, not only as an entity but also as part of a brain circuit through a more integrative approach.

History of Magnetic Resonance Imaging: A Trip Down Memory Lane.

The history of magnetic resonance imaging (MRI) is closely linked to our improved understanding of memory systems, be it in normal functioning or altered due to pathologies. Over the years, brain imaging using MRI has moved from simple volumetric imaging to complex analysis using multiple sequences, allowing the measurement of microstructural integrity and brain activation through a dedicated task or at rest. This review aims at showing how the advent and evolution of magnetic resonance imaging has shaped a better understanding of memory and brain function in humans. We will give a brief overview on the history of MRI, how its evolution brought about concomitant improvement in our understanding of memory systems, going from final-stage observation to risk-prediction via the detection of subtle, but important, alterations in normal brain functioning.

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.

Brain Substrates of Time-Based Prospective Memory Decline in Aging: A Voxel-Based Morphometry and Diffusion Tensor Imaging Study.

Time-based prospective memory (TBPM) allows us to remember to perform intended actions at a specific time in the future. TBPM is sensitive to the effects of age, but the neural substrates of this decline are still poorly understood. The aim of the present study was thus to better characterize the brain substrates of the age-related decline in TBPM, focusing on macrostructural gray matter and microstructural white matter integrity. We administered a TBPM task to 22 healthy young (26 ± 5.2 years) and 23 older (63 ± 5.9 years) participants, who also underwent volumetric magnetic resonance imaging and diffusion tensor imaging scans. Neuroimaging analyses revealed lower gray matter volumes in several brain areas in older participants, but these did not correlate with TBPM performance. By contrast, an age-related decline in fractional anisotropy in several white-matter tracts connecting frontal and occipital regions did correlate with TBPM performance, whereas there was no significant correlation in healthy young subjects. According to the literature, these tracts are connected to the anterior prefrontal cortex and the thalamus, 2 structures involved in TBPM. These results confirm the view that a disconnection process occurs in aging and contributes to cognitive decline.