Episodic Memory Assessment and Remediation in Normal and Pathological Aging Using Virtual Reality: A Mini Review

Life expectancy is constantly increasing in developed countries. Unfortunately, a longer life does not always correspond to a healthier life, as even normal aging is associated with cognitive decline and increased risk factors for neurodegenerative diseases. Episodic memory (EM) is one of the most vulnerable cognitive functions in aging, and its decline is the hallmark of typical Alzheimer’s disease. This memory system is defined as the ability to acquire and recollect personally experienced episodes associated with a specific affective, spatial, and temporal context. However, most of the neuropsychological and experimental tasks currently employed to assess EM consist in learning simple material (e.g., list of words) in highly stereotyped contexts. In the same vein, classical paper-and-pencil or numeric remediation tools have shown their limitations in the transfer of acquired skills to daily life. Virtual reality (VR), thanks to its immersive properties, and the possibility of delivering realistic and complex scenarios, seems a promising tool to address the limitations of the assessment and remediation of EM. Here, we review existing studies employing VR in normal and pathological aging to assess and reeducate EM. Overall, we show that VR has been mainly used via non-immersive systems. Further studies should, therefore, test the impact of different degrees of immersion. Moreover, there is a lack of VR remediation tools specifically targeting EM. We propose that future studies should fill this gap, addressing in particular the adaptivity of VR remediation protocols

Episodic Memory Assessment and Remediation in Normal and Pathological Aging Using Virtual Reality: A Mini Review

Life expectancy is constantly increasing in developed countries. Unfortunately, a longer life does not always correspond to a healthier life, as even normal aging is associated with cognitive decline and increased risk factors for neurodegenerative diseases. Episodic memory (EM) is one of the most vulnerable cognitive functions in aging, and its decline is the hallmark of typical Alzheimer’s disease. This memory system is defined as the ability to acquire and recollect personally experienced episodes associated with a specific affective, spatial, and temporal context. However, most of the neuropsychological and experimental tasks currently employed to assess EM consist in learning simple material (e.g., list of words) in highly stereotyped contexts. In the same vein, classical paper-and-pencil or numeric remediation tools have shown their limitations in the transfer of acquired skills to daily life. Virtual reality (VR), thanks to its immersive properties, and the possibility of delivering realistic and complex scenarios, seems a promising tool to address the limitations of the assessment and remediation of EM. Here, we review existing studies employing VR in normal and pathological aging to assess and reeducate EM. Overall, we show that VR has been mainly used via non-immersive systems. Further studies should, therefore, test the impact of different degrees of immersion. Moreover, there is a lack of VR remediation tools specifically targeting EM. We propose that future studies should fill this gap, addressing in particular the adaptivity of VR remediation protocols

Loss of brain inter-frequency hubs in Alzheimer's disease

Alzheimer's disease (AD) causes alterations of brain network structure and function. The latter consists of connectivity changes between oscillatory processes at different frequency channels. We proposed a multi-layer network approach to analyze multiple-frequency brain networks inferred from magnetoencephalographic recordings during resting-states in AD subjects and age-matched controls. Main results showed that brain networks tend to facilitate information propagation across different frequencies, as measured by the multi-participation coefficient (MPC). However, regional connectivity in AD subjects was abnormally distributed across frequency bands as compared to controls, causing significant decreases of MPC. This effect was mainly localized in association areas and in the cingulate cortex, which acted, in the healthy group, as a true inter-frequency hub. MPC values significantly correlated with memory impairment of AD subjects, as measured by the total recall score. Most predictive regions belonged to components of the default-mode network that are typically affected by atrophy, metabolism disruption and amyloid-beta deposition. We evaluated the diagnostic power of the MPC and we showed that it led to increased classification accuracy (78.39%) and sensitivity (91.11%). These findings shed new light on the brain functional alterations underlying AD and provide analytical tools for identifying multi-frequency neural mechanisms of brain diseases.Comment: 27 pages, 6 figures, 3 tables, 3 supplementary figure

Potential Role of Anti-interleukin (IL)-6 Drugs in the Treatment of COVID-19: Rationale, Clinical Evidence and Risks

The epidemic due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has been spreading globally, raising increasing concerns. This public health emergency has triggered a race to find medications to improve the prognosis of this disease. There is currently great interest in drug repositioning to manage SARS-CoV-2 infection, that is, the evaluation of the potential benefits of a drug that has already been proven safe and effective in humans for other approved indications. As interleukin-6 (IL-6) acts as a key driver of the inflammation associated with coronavirus disease 2019 (COVID-19), IL-6 and IL-6 receptor (IL-6R) inhibition appear to be promising targets for the treatment of COVID-19 patients. It is important to critically analyze the available evidence concerning the use of the available anti-IL-6 (siltuximab) and anti-IL-6R (tocilizumab and sarilumab) agents in COVID-19 patients, in terms of both benefit and risk. In this review, the pathogenesis of the cytokine storm induced by COVID-19, the role of IL-6 in this cytokine storm, the rationale for the use of anti-IL-6 agents, and key information on potential benefits and safety monitoring of these biologicals in COVID-19 patients is discussed

Young and Older Adults Benefit From Sleep, but Not From Active Wakefulness for Memory Consolidation of What-Where-When Naturalistic Events

An extensive psychological literature shows that sleep actively promotes human episodic memory (EM) consolidation in younger adults. However, evidence for the benefit of sleep for EM consolidation in aging is still elusive. In addition, most of the previous studies used EM assessments that are very different from everyday life conditions and are far from considering all the hallmarks of this memory system. In this study, the effect of an extended period of sleep was compared to the effect of an extended period of active wakefulness on the EM consolidation of naturalistic events, using a novel (What-Where-When) EM task, rich in perceptual details and spatio-temporal context, presented in a virtual environment. We investigated the long-term What-Where-When and Details binding performances of young and elderly people before and after an interval of sleep or active wakefulness. Although we found a noticeable age-related decline in EM, both age groups benefited from sleep, but not from active wakefulness. In younger adults, only the period of sleep significantly enhanced the capacity to associate different components of EM (binding performance) and more specifically the free recall of what-when information. Interestingly, in the elderly, sleep significantly enhanced not only the recall of factual elements but also associated details and contextual information as well as the amount of high feature binding (i.e., What-Where-When and Details). Thus, this study evidences the benefit of sleep, and the detrimental effect of active wakefulness, on long-term feature binding, which is one of the core characteristics of EM, and its effectiveness in normal aging. However, further research should investigate whether this benefit is specific to sleep or more generally results from the effect of a post-learning period of reduced interference, which could also concern quiet wakefulness

Diagnostic and surgical management of primary central nervous system angioleiomyoma: A case report and literature review

Angioleiomyoma (ALM) is a benign smooth muscle neoplasm that mainly occurs in lower extremities subcutaneous tissue and generally affects middle-aged adults. This tumor histotype may rarely localize intracranially, although only a few cases have been described in the literature. We report a case of intracranial ALM, whose differential diagnosis has been particularly challenging, and firstly provide a comprehensive radiological and intra-operative evaluation of a such rare entity. This represents also the first report of the use of intraoperative confocal microscopy in ALM and the first documented short-term recurrence. At this regard, a scoping literature review has been conducted with the aim of presenting the major clinical and diagnostic features along with the proposed therapeutic strategies

Alzheimers Dement

Introduction: The free and cued selective reminding test is used to identify memory deficits in mild cognitive impairment and demented patients. It allows assessing three processes: encoding, storage, and recollection of verbal episodic memory. Methods: We investigated the neural correlates of these three memory processes in a large cohort study. The Memento cohort enrolled 2323 outpatients presenting either with subjective cognitive decline or mild cognitive impairment who underwent cognitive, structural MRI and, for a subset, fluorodeoxyglucose-positron emission tomography evaluations. Results: Encoding was associated with a network including parietal and temporal cortices; storage was mainly associated with entorhinal and parahippocampal regions, bilaterally; retrieval was associated with a widespread network encompassing frontal regions. Discussion: The neural correlates of episodic memory processes can be assessed in large and standardized cohorts of patients at risk for Alzheimer's disease. Their relation to pathophysiological markers of Alzheimer's disease remains to be studied

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Systèmes de mémoire et distorsions mnésiques : approches neuropsychologique et neurophysiologique

The relationship between episodic memory (EM) and semantic memory (SM) encompasses a major interest for understanding the functional architecture of the long-term memory and the mechanisms underlying the different types of memory deficits. Our main objective was to study the functionning of these two memory systems and their dysfunction, through the study of symptoms known as 'negative', such as forgetfulness and positive symptoms, such as confabulation. The first part of this work concerns the study of the organization of these two memory systems using a paradigm suitable for magnetoencephalography (MEG). A first MEG study in healthy elderly subjects showed a clear dissociation between neurophysiological correlates of EM for famous and unknown faces, showing the interdependence between EM and SM in faces recognition. A second comparative study between a group of patients with Alzheimer's disease (AD) and a group of healthy subjects performed with the same experimental paradigm, allowed us to show an alteration of the relationship between EM and SM from a neuropsychological point of view and the physiopathological correlates of memory deficits in AD. The second part focuses on the expression of the dysfunction of the EM and SM in confabulation. Our studies show that confabulation cannot be considered as a pure memory deficit, but rather as a disorder of consciousness, especially temporal consciousness. Overall, our findings suggest that the link between memory, consciousness and temporality encompasses a major interest in studying the organization of memory systems and in a better understanding of memory disordersLa relation entre mémoire épisodique (ME) et mémoire sémantique (MS) recouvre un intérêt majeur pour la compréhension de l'architecture fonctionnelle de la mémoire à long terme, ainsi que pour la compréhension des mécanismes sous-jacents aux différents types de déficits mnésiques. Notre objectif principal a été d'étudier le fonctionnement de ces deux systèmes mnésiques ainsi que leur dysfonctionnement, à travers l'étude des symptômes dits 'négatifs', tels que les oublis, et les symptômes positifs, tels que la confabulation. La première partie de ce travail concerne l'étude de l'organisation de ces deux systèmes mnésiques à l'aide d'un paradigme adapté à la magnétoencéphalographie (MEG). Une première étude réalisée en MEG chez des sujets âgés sains révèle une dissociation claire entre les corrélats neurophysiologiques de la ME pour les visages célèbres et inconnus, démontrant l'interdépendance entre ME et MS dans la reconnaissance des visages. Une deuxième étude comparative, entre un groupe de patients atteints de Maladie d'Alzheimer (MA) et un groupe de sujets sains, nous a permis de caractériser les corrélats physiopathologiques des déficits mnésiques dans la MA.La deuxième partie est centrée sur l'expression du dysfonctionnement de la ME et de la MS dans la confabulation. Nos études révèlent que la confabulation ne peut pas être considérée comme un pur déficit mnésique, mais plutôt comme un dysfonctionnement de la conscience temporelle. L'ensemble de ces travaux suggère que le lien entre mémoire, conscience et temporalité recouvre un intérêt majeur dans l'étude de l'organisation des systèmes mnésiques ainsi que pour une meilleure compréhension des pathologies mnésique

Episodic foresight in normal cognitive and pathological aging

International audienceRésumé. Les recherches de cette dernière décennie témoignent de l’intérêt croissant pourla capacité de l’individu à se projeter dans le futur et à imaginer/prévoir des évènementsdans un futur personnel. Différentes théories ont été proposées pour essayer d’expliquerles mécanismes cognitifs sous-jacents à cette capacité. Dans cet article, nous nous intéressons à la capacité de prospection épisodique dans le vieillissement cognitif normal etpathologique en particulier dans la maladie d’Alzheimer et la démence sémantique. Nousdiscuterons ensuite le rôle des représentations sémantiques personnelles en fonction dela distance temporelle dans la projection épisodique en proposant un nouveau modèle(TEDIFT) qui postule l’intervention de deux processus, la continuité phénoménologiqueou la continuité sémantique en fonction de la distance temporelle de prospection ou derécupération