Effect of multiple sclerosis and aging on prospective memory using the ecological test of prospective memory.

OBJECTIVE: Prospective memory (PM) is the ability to remember to produce an action at a specific moment in the future signaled by the occurrence of a specific event (event-based [EB] condition), a time or a time interval (time-based [TB] condition). Detection of the appropriate moment corresponds to the prospective component, while production of the appropriate action corresponds to the retrospective component. Although PM difficulties have been reported in healthy aging and in association with multiple sclerosis (MS), PM has not been examined in older persons with MS (PwMS). The main objective of this study was to investigate whether the decline in PM performance with advancing age is influenced by the presence of MS. This study also aimed to clarify the type of PM impairment (prospective vs. retrospective component in TB and EB conditions) in MS as a function of age. METHOD: A total of 80 participants were recruited and separated into four groups: older PwMS (n = 20), younger PwMS (n = 20), older controls (n = 20), and younger controls (n = 20). PM and its components were measured using the Test Ecologique de Mémoire Prospective (TEMP), an experimental ecological tool using naturalistic stimuli developed by our laboratory that has been validated in previous studies. RESULTS: On the TEMP total score, a two-way analysis of covariance showed a main effect of age, a main effect of the presence of MS, as well as a significant Age × Disease interaction. Direct comparison between EB and TB conditions revealed that for the prospective component, only older PwMS had more difficulty in the TB than in the EB condition, whereas the retrospective component score was significantly lower in the TB than in the EB condition in all groups except in younger controls. CONCLUSIONS: The TEMP revealed a marked impairment in PM in older PwMS compared to older controls and young PwMS. This impairment was particularly evident on the prospective component in the TB condition. Retrospective difficulties noted in the TB condition in all, but younger controls reflect the arbitrary nature of the cue-action link that is particularly sensitive to episodic memory difficulties often observed in aging and MS. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Prospective memory in multiple sclerosis: clinical utility of the Miami Prospective Memory Test.

Objective: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system that frequently affects cognition. Persons with MS (PwMS) complain of difficulties with prospective memory (PM), the capacity to remember to perform an intended action at the appropriate moment in the future. The objective of this study was to assess the clinical utility of the Miami Prospective Memory Test (MPMT) in detecting PM deficits in MS. The test is brief, easy to administer and accessible, and allows direct comparison between scores on event- and time-based conditions. A secondary objective was to examine the relationship between PM performance and cognitive functioning. Method: Eighty-four PwMS between 27 and 78 years old were compared to 50 age-, sex- and education-matched healthy adults on the MPMT. Results: Time-based (TB) scores, but not event-based (EB) scores, were significantly lower in PwMS than in healthy adults. The MPMT showed good internal consistency, and correlations were found with disability assessed by the Expanded Disability Status Scale (EDSS). PM was also correlated with memory and executive/attention functioning. Conclusions: This study supports the clinical utility of the MPMT in assessing the presence of PM deficits in PwMS especially under TB constraints.

Children's perspectives on friendships and socialization during the COVID-19 pandemic: A qualitative approach.

BACKGROUND: Good quality friendships and relationships are critical to the development of social competence and are associated with quality of life and mental health in childhood and adolescence. Through social distancing and isolation restrictions, the COVID-19 pandemic has had an impact on the way in which youth socialize and communicate with friends, peers, teachers and family on a daily basis. In order to understand children's social functioning during the pandemic, it is essential to gather information on their experiences and perceptions concerning the social changes unique to this period. The objective of this study was to document children and adolescents' perspectives regarding their social life and friendships during the COVID-19 pandemic, through qualitative interviews. METHODS: Participants (N = 67, 5-14 years) were recruited in May and June 2020. Semi-structured interviews were conducted via a videoconferencing platform. A thematic qualitative analysis was conducted based on the transcribed and coded interviews (NVivo). RESULTS: The upheavals related to the pandemic provoked reflection among the participants according to three main themes, each of which included sub-themes: (1) the irreplaceable nature of friendship, (2) the unsuspected benefits of school for socialization and (3) the limits and possibilities of virtual socialization. CONCLUSIONS: The collection of rich, qualitative information on the perspectives of children and adolescents provides a deeper understanding of the consequences of the pandemic on their socialization and psychological health and contributes to our fundamental understanding of social competence in childhood.

Multimodal emotion perception in young and elderly patients with multiple sclerosis.

BACKGROUND: Studies suggest that emotion recognition and empathy are impaired in patients with MS (pwMS). Nonetheless, most studies are restricted to young samples, to facial emotion recognition and to self-report assessments of empathy. The aims of this study are to determine the impact of MS and age on multimodal emotion recognition (facial emotions and vocal emotional bursts) and on socioemotional sensitivity (as reported by the participants and their informants). We also aim to investigate the associations between emotion recognition, socioemotional sensitivity, and cognitive measures. METHODS: We recruited 13 young healthy controls (HC), 14 young pwMS, 14 elderly HC and 15 elderly pwMS. They underwent a short neuropsychological battery, an experimental emotion recognition task including facial emotions and vocal emotional bursts. Both participants and their study informants completed the Revised-Self Monitoring Scale (RSMS) to assess the participant's socioemotional sensitivity. RESULTS: There was a significant effect of age and group on recognition of both facial emotions and emotional vocal bursts, HC performing significantly better than pwMS, and young participants performing better than elderly participants (no interaction effect). The same effects were observed on self-reported socioemotional sensitivity. However, lower socioemotional sensitivity in pwMS was not reported by the informants. Finally, multimodal emotion recognition did not correlate with socioemotional sensitivity, but it correlated with global cognitive severity. CONCLUSION: PwMS present with multimodal emotion perception deficits. Our results extend previous findings of decreased emotion perception and empathy to a group of elderly pwMS, in which advancing age does not accentuate these deficits. However, the decreased socioemotional sensitivity reported by pwMS does not appear to be observed by their relatives, nor to correlate with their emotion perception impairments. Future studies should investigate the real-life impacts of emotion perception deficits in pwMS.

The effects of aging and disease duration on cognition in multiple sclerosis.

OBJECTIVES: Multiple sclerosis (MS) is a disease of the central nervous system that can interfere with cognitive functions. The purpose of this study is to document the impact of MS, aging and disease duration on cognitive functioning as both life expectancy and incidence of the disease among persons with MS (PwMS) aged 50 years and over (late-onset MS) are increasing in the last two decades. METHODS: Exhaustive neuropsychological evaluation was performed in 84 PwMS (30 young, 30 elderly adult-onset, 25 elderly late-onset) and 50 control participants (25 young, 24 elderly). ANCOVAs and hierarchical linear regressions were used to meet the objectives. RESULTS: Interaction effects were found between age and presence of MS on higher executive function and information processing speed/working memory. After controlling for confounding variables (fatigue, quality of life, depression, MS course, comorbidity), results demonstrated an important role of age on all cognitive functions but only a trend of disease duration on information processing speed/working memory. CONCLUSION: Decline in higher executive functions and information processing speed/working memory in aging is accentuated by the presence of MS, but the impact of age and MS on memory are independent. Age appears to be the variable having the most important role on cognition.

Detecting Subtle Cognitive Impairment in Multiple Sclerosis with the Montreal Cognitive Assessment.

BACKGROUND: Although cognitive deficits are frequent in multiple sclerosis (MS), screening for them with tools such as the Montreal Cognitive Assessment (MoCA) test is usually not performed unless there is a subjective complaint. The Multiple Sclerosis Neuropsychological Questionnaire (MSNQ) is among the instruments most commonly used to assess self-reported subjective complaints in MS. Nonetheless, it does not always accurately reflect cognitive status; many patients with cognitive deficits thus fail to receive appropriate referral for detailed neuropsychological evaluation. The objective of this study was to examine the validity of the MoCA test to detect the presence of objective cognitive deficits among patients with MS without subjective complaints using the Minimal Assessment of Cognitive Function in MS (MACFIMS) as the gold standard. METHODS: The sample included 98 patients who were recruited from a university hospital MS clinic. The MSNQ was used to select patients without subjective cognitive complaints who also completed the MACFIMS, MoCA test and MSQOL-54. RESULTS: 23.5% of patients without subjective cognitive complaints had evidence of objective cognitive impairment on the MACFIMS (z score < -1.5 on two or more tests). The MoCA had a sensitivity of 87% and a specificity of 68% for detecting objective cognitive impairment in this patient population using a cut-off score of 27. CONCLUSION: A significant proportion of patients without self-reported cognitive impairment do have evidence of cognitive deficits on more exhaustive cognitive assessment. The MoCA is a rapid screening test that could be used to target patients for whom a more detailed neuropsychological assessment would be recommended.

Thalamic and hippocampal volume associated with memory functions in multiple sclerosis.

OBJECTIVES: Although multiple sclerosis (MS) has long been considered to primarily affect white matter, it is now recognized that cognitive deficits in MS are also related to neocortical, thalamic and hippocampal damage. However, the association between damage to these structures and memory deficits in MS is unclear. This study examines whether MS patients with cognitive impairment have a reduction of hippocampal and/or thalamic volumes compared to cognitively intact patients, and whether these volume reductions correlate with various aspects of memory function. METHODOLOGY: Volumetric MRI measures of thalamus and hippocampus of forty-one patients with MS were performed. The patients were divided in two groups depending on the presence or absence of cognitive impairment, based on their neuropsychological tests scores. RESULTS: Right hippocampal volume was found to be associated with learning, and the left thalamic volume was found to predict performance in verbal memory. Cognitively impaired patients had a tendency to have a reduced left thalamic volume compared to cognitively intact patients. CONCLUSIONS: This study does not support a direct relationship between hippocampal atrophy and verbal memory. These results add to the growing evidence of the involvement of thalamus in cognitive impairment in MS and its association with verbal memory deficits.

Prospective memory impairment in multiple sclerosis: a review.

OBJECTIVE: Multiple sclerosis (MS) is a progressive disease of the central nervous system affecting information processing speed, episodic memory, attention, and executive functions. MS patients also often report prospective memory (PM) failures that directly impact their functional autonomy, including professional and social life. The purpose of this paper was to review the literature concerning the assessment and remediation of PM deficits in MS. METHOD: The literature pertaining to PM impairment in MS was carefully reviewed using PubMed, PsyINFO, and Google Scholar, as well as cross-references from the articles published on this topic. Since PM rehabilitation in MS patients is still in its infancy, this review mainly focuses on studies that have directly assessed PM through various measures including questionnaires, standardized clinical tests, and experimental procedures. CONCLUSION: This literature review confirms the presence of PM deficits in MS patients, even in the early stages of the disease. A further need for controlled studies on PM assessment and PM interventions in patients with MS is stressed.

Broad Infiltration of Macrophages Leads to a Proinflammatory State in Streptozotocin-Induced Hyperglycemic Mice.

Chronic diseases are often associated with altered inflammatory response, leading to increased host vulnerability to new inflammatory challenges. Employing streptozotocin (STZ)-induced diabetes as a model, we further investigate mechanisms leading to enhanced neutrophil (polymorphonuclear leukocytes [PMN]) responses under hyperglycemia and compare them with those under chronic colitis. We show that, different from colitis under which the PMN response is significantly potentiated, the existence of a proinflammatory state associated with broad increases in macrophages in various organs plays a dominant role in promoting the PMN inflammatory response in diabetic mice. Studies of PMN infiltration during zymosan-induced peritonitis reveal that hyperglycemia enhances PMN recruitment not through inducing a high level of IL-17, which is the case in colitis, but through increasing F4/80+ macrophages in the peritoneal cavity, resulting in elevations of IL-6, IL-1ß, TNF-α, and CXCL1 production. Insulin reversal of hyperglycemia, but not the neutralization of IL-17, reduces peritoneal macrophage numbers and ameliorates PMN infiltration during peritonitis. Significantly increased macrophages are also observed in the liver, kidneys, and intestines under hyperglycemia, and they are attributable to exacerbated nephropathy and colitis when inflammatory conditions are induced by doxorubicin and dextran sulfate sodium, respectively. Furthermore, analyses of monocyte production and macrophage proliferation in tissues suggest that significant monocytosis of inflammatory F4/80+Gr-1+ monocytes from the spleen and macrophage proliferation in situ synergistically contribute to the increased macrophage population under hyperglycemia. In conclusion, our results demonstrate that STZ-induced hyperglycemic mice develop a systemic proinflammatory state mediated by broad infiltration of macrophages.

Prospective memory in multiple sclerosis: The impact of cue distinctiveness and executive functioning.

OBJECTIVE: Prospective memory (PM), the ability to remember to do something at the appropriate time in the future, is crucial in everyday life. One way to improve PM performance is to increase the salience of a cue announcing that it is time to act. Multiple sclerosis (MS) patients often report PM failures and there is growing evidence of PM deficits among this population. However, such deficits are poorly characterized and their relation to cognitive status remains unclear. To better understand PM deficits in MS patients, this study investigated the impact of cue salience on PM, and its relation to retrospective memory (RM) and executive deficits. METHODS: Thirty-nine (39) MS patients were compared to 18 healthy controls on a PM task modulating cue salience during an ongoing general knowledge test. RESULTS: MS patients performed worse than controls on the PM task, regardless of cue salience. MS patients' executive functions contributed significantly to the variance in PM performance, whereas age, education and RM did not. Interestingly, low- and high-executive patients' performance differed when the cue was not salient, but not when it was, suggesting that low-executive MS patients benefited more from cue salience. CONCLUSIONS: These findings add to the growing evidence of PM deficits in MS and highlight the contribution of executive functions to certain aspects of PM. In low-executive MS patients, high cue salience improves PM performance by reducing the detection threshold and need for environmental monitoring.

Cd47-Sirpα interaction and IL-10 constrain inflammation-induced macrophage phagocytosis of healthy self-cells.

Rapid clearance of adoptively transferred Cd47-null (Cd47(-/-)) cells in congeneic WT mice suggests a critical self-recognition mechanism, in which CD47 is the ubiquitous marker of self, and its interaction with macrophage signal regulatory protein α (SIRPα) triggers inhibitory signaling through SIRPα cytoplasmic immunoreceptor tyrosine-based inhibition motifs and tyrosine phosphatase SHP-1/2. However, instead of displaying self-destruction phenotypes, Cd47(-/-) mice manifest no, or only mild, macrophage phagocytosis toward self-cells except under the nonobese diabetic background. Studying our recently established Sirpα-KO (Sirpα(-/-)) mice, as well as Cd47(-/-) mice, we reveal additional activation and inhibitory mechanisms besides the CD47-SIRPα axis dominantly controlling macrophage behavior. Sirpα(-/-) mice and Cd47(-/-) mice, although being normally healthy, develop severe anemia and splenomegaly under chronic colitis, peritonitis, cytokine treatments, and CFA-/LPS-induced inflammation, owing to splenic macrophages phagocytizing self-red blood cells. Ex vivo phagocytosis assays confirmed general inactivity of macrophages from Sirpα(-/-) or Cd47(-/-) mice toward healthy self-cells, whereas they aggressively attack toward bacteria, zymosan, apoptotic, and immune complex-bound cells; however, treating these macrophages with IL-17, LPS, IL-6, IL-1ß, and TNFα, but not IFNγ, dramatically initiates potent phagocytosis toward self-cells, for which only the Cd47-Sirpα interaction restrains. Even for macrophages from WT mice, phagocytosis toward Cd47(-/-) cells does not occur without phagocytic activation. Mechanistic studies suggest a PKC-Syk-mediated signaling pathway, to which IL-10 conversely inhibits, is required for activating macrophage self-targeting, followed by phagocytosis independent of calreticulin Moreover, we identified spleen red pulp to be one specific tissue that provides stimuli constantly activating macrophage phagocytosis albeit lacking in Cd47(-/-) or Sirpα(-/-) mice.

Role of executive functions in prospective memory in multiple sclerosis: Impact of the strength of cue-action association.

OBJECTIVES: Patients diagnosed with multiple sclerosis (MS) often report prospective memory (PM) deficits. Although PM is important for daily functioning, it is not formally assessed in clinical practice. The aim of this study was to examine the role of executive functions in MS patients' PM revealed by the effect of strength of cue-action association on PM performance. METHOD: Thirty-nine MS patients were compared to 18 healthy controls matched for age, gender, and education on a PM task modulating the strength of association between the cue and the intended action. RESULTS: Deficits in MS patients affecting both prospective and retrospective components of PM were confirmed using 2 × 2 × 2 mixed analyses of variance (ANOVAs). Among patients, multiple regression analyses revealed that the impairment was modulated by the efficiency of executive functions, whereas retrospective memory seemed to have little impact on PM performance, contrary to expectation. More specifically, results of 2 × 2 × 2 mixed-model analyses of covariance (ANCOVAs) showed that low-executive patients had more difficulty detecting and, especially, retrieving the appropriate action when the cue and the action were unrelated, whereas high-executive patients' performance seemed to be virtually unaffected by the cue-action association. CONCLUSIONS: Using an objective measure, these findings confirm the presence of PM deficits in MS. They also suggest that such deficits depend on executive functioning and can be reduced when automatic PM processes are engaged through semantic cue-action association. They underscore the importance of assessing PM in clinical settings through a cognitive evaluation and offer an interesting avenue for rehabilitation.

Loss of Cell Surface CD47 Clustering Formation and Binding Avidity to SIRPα Facilitate Apoptotic Cell Clearance by Macrophages.

CD47, a self recognition marker expressed on tissue cells, interacts with immunoreceptor SIRPα expressed on the surface of macrophages to initiate inhibitory signaling that prevents macrophage phagocytosis of healthy host cells. Previous studies suggested that cells may lose surface CD47 during aging or apoptosis to enable phagocytic clearance. In the current study, we demonstrate that the level of cell surface CD47 is not decreased, but the distribution pattern of CD47 is altered, during apoptosis. On nonapoptotic cells, CD47 molecules are clustered in lipid rafts forming punctates on the surface, whereas on apoptotic cells, CD47 molecules are diffused on the cell surface following the disassembly of lipid rafts. We show that clustering of CD47 in lipid rafts provides a high binding avidity for cell surface CD47 to ligate macrophage SIRPα, which also presents as clusters, and elicits SIRPα-mediated inhibitory signaling that prevents phagocytosis. In contrast, dispersed CD47 on the apoptotic cell surface is associated with a significant reduction in the binding avidity to SIRPα and a failure to trigger SIRPα signal transduction. Disruption of plasma membrane lipid rafts with methyl-ß-cyclodextrin diffuses CD47 clusters, leading to a decrease in the cell binding avidity to SIRPα and a concomitant increase in cells being engulfed by macrophages. Taken together, our study reveals that CD47 normally is clustered in lipid rafts on nonapoptotic cells but is diffused in the plasma membrane when apoptosis occurs; this transformation of CD47 greatly reduces the strength of CD47-SIRPα engagement, resulting in the phagocytosis of apoptotic cells.

CD47 deficiency does not impede polymorphonuclear neutrophil transmigration but attenuates granulopoiesis at the postacute stage of colitis.

Previous studies have suggested that CD47, an essential cell-surface protein, plays an important role in polymorphonuclear neutrophil (PMN) transmigration across tissue cells and extracellular matrix. In the current study, the role of CD47 in PMN transmigration and infiltration into tissues was further evaluated by investigating the function of CD47(-/-) PMN and inflammatory conditions induced in CD47(-/-) mice. Using in vitro time-course assays, we found that CD47(-/-) PMN exhibited no impediment, but slightly enhanced response to and transmigration toward, the chemoattractant fMLF. In vivo analysis in CD47(-/-) mice by inducing acute peritonitis and aggressive colitis observed consistent results, indicating that both PMN and monocytes effectively infiltrated inflammatory sites despite the absence of CD47 on these leukocytes or the surrounding tissue cells. Although PMN transmigration was not delayed in CD47(-/-) mice, fewer PMN were found in the intestine at the postacute/chronic stage of chronic colitis induced with sustained low-dose dextran sulfate sodium. Further analysis suggested that the paucity of PMN accumulation was attributable to attenuated granulopoiesis secondary to assessed lower levels of IL-17. Administration of exogenous IL-17A markedly increased PMN availability and rapidly rendered severe colitis in CD47(-/-) mice under dextran sulfate sodium treatment.