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ObjectiveTo investigate, in Korsakoff patients (KS), cognitive and brain changes over months and up to 10 years after the diagnosis.MethodsTwo groups of 8 KS patients underwent neuropsychological, motor and neuroimaging investigations including structural MRI and 18F-FDG-PET. The KSC group was examined early after the KS diagnosis (KSC-T1) and one year later (KSC-T2). The KSR group 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 nor brain deterioration occurred over time in KS patients. 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 affecting notably 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.

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 as a relevant tool 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 (including five 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 is in accordance 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. On the opposite, 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 (/6) on the episodic memory subtest of BEARNI could be considered at risk of developing KS and exhibited the lowest episodic memory performance on the neuropsychological battery. Conclusions: These findings suggest that BEARNI is a relevant tool to detect severe memory impairments, thus making early identification of AUD patients at high risk of developing KS possible.

In alcohol use disorder, drinking cessation is frequently associated with an alcohol withdrawal syndrome. Early in abstinence (within the first two 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 gray 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 gray 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, gray 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.

Sleep plays a crucial role in memory consolidation. Recent data in rodents and young adults revealed that fast spindle band power fluctuates at a 0.02-Hz infraslow scale during non-rapid eye movement (NREM) sleep. These fluctuations result from a periodic temporal clustering of spindles and may modulate sleep maintenance and memory consolidation. With age, sleep undergoes substantial changes but age-related changes in spindle clustering have never been investigated. Polysomnography data were collected in 147 older (mean age ± SD: 69.3 ± 4.1 years) and 32 young-middle aged (34.5 ± 10.9 years) adults. Sleep-dependent memory consolidation was assessed in a subsample of 57 older adults using a visuospatial memory task. We analyzed power fluctuations in fast spindle frequency band, detected fast spindles and quantified their clustering during the night separating encoding and retrieval. Fast spindle band power fluctuated at a 0.02-Hz infraslow scale in young-middle aged and older adults. However, the proportion of clustered fast spindles decreased non-linearly with age (p < 0.001). This effect was not mediated by NREM sleep fragmentation. The clustering level of fast spindles modulated their characteristics (p < 0.001). Finally, the mean size of spindle clusters was positively associated with memory consolidation (p = 0.036) and negatively with NREM sleep micro-arousals density (p = 0.033). These results suggest that clusters of fast spindles may constitute stable sleep periods promoting off-line processes such as memory consolidation. We emphasize the relevance of considering spindle dynamics, obviously impaired during ageing, to understand the impact of age-related sleep changes on memory.

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