A systematic review and meta-analysis of socio-cognitive impairments in multiple sclerose.

Socio-cognitive impairment is frequent in multiple sclerosis (MS). However, little is known about the relationship between other potentially relevant clinical symptoms (i.e., cognition, depression, fatigue) and the degree of socio-cognitive impairment, and neural mechanisms underlying socio-cognitive deficits in MS. Therefore, we meta-analytically quantified socio-cognitive impairment in MS. A systematic literature search in MEDLINE Ovid, Web of Science Core Collection, CENTRAL, and PsycInfo was conducted until December 2022. Studies investigating affective or cognitive theory of mind (a/cToM), visual perspective taking (VPT) and social decision making (SDM) in MS patients relative to healthy controls were included. Risk-of-bias (RoB) was assessed using the CLARITY group "Tool for Assessing RoB in Cohort Studies". Mediation analysis investigated the contribution of clinical symptoms to socio-cognitive impairment. In total, n = 8534 studies were screened, 58 were included in the systematic review, 27 in the meta-analyses. Most studies were rated with a moderate RoB. Meta-analyses confirmed impairment of both aToM and cToM in MS patients, with larger effect sizes for aToM. Mediation analysis demonstrated that higher levels of fatigue selectively predicted the degree of cToM impairment. There was insufficient data available to quantify impairment in other socio-cognitive domains. Fourteen structural and functional imaging studies were identified and characterized by substantial heterogeneity. Summarized, this study confirmed substantial socio-cognitive impairment in MS and highlights the potential exacerbating role of comorbid clinical symptoms. We identify several evidence gaps that need to be addressed in future large-scale studies using comprehensive and coordinated assessments of socio-cognitive parameters, potential mediators, and neural correlates.Trial registration: The pre-registered review protocol can be assessed at www.crd.york.ac.uk/PROSPERO/ (ID: CRD42020206225).

Relationship between physical activity and coping with stress in people with multiple sclerosis: A moderated mediation model with self-efficacy and disability level as variables / Relación entre actividad física y afrontamiento del estrés en personas con esclerosis múltiple: un modelo de mediación moderada con autoeficacia y nivel de discapacidad como variables

Purpose: An increasing number of studies support the beneficial relationship between physical activity and stress coping in people with multiple sclerosis (MS). However, there has been limited understanding of the variables that may influence the nature of this relationship. Therefore, based on the social-cognitive framework and previous research, we aimed to examine the association between the habitual physical activity of people with MS and their coping effectiveness. Furthermore, we sought to determine the extent to which self-efficacy acts as a mediator in this relationship, considering the level of disability as a moderator variable. Methods: In this cross-sectional study, a total of 351 people with MS participated. The participants were asked to complete several assessment tools, including the Mini-COPE Inventory for Measurement—Coping with Stress, the Generalized Self-Efficacy Scale, and the Godin Leisure-Time Exercise Questionnaire. Additionally, a neurologist assessed the severity of the disease using the Expanded Disability Status Scale. Information on the demographic and clinical characteristics of the participants was collected via a self-report survey. Two moderated mediation analyses were conducted as part of the study. Results: The study findings indicated a positive correlation between engagement in physical activity and self-efficacy among participants with high and medium disability levels. This, in turn, demonstrated a positive association with effective stress-coping strategies and a negative association with ineffective coping methods. In particular, a significant relationship was observed between involvement in physical activity and self-efficacy in participants with high disability, while it was not statistically significant in participants with low disability.(AU)

Cognitive rehabilitation program in patients with multiple sclerosis: A pilot study.

INTRODUCTION: In recent years, there has been an increase of studies dedicated to cognitive rehabilitation in patients with multiple sclerosis (MS); however, few of these analyze the impact on such variables as cognitive reserve. The study aims to explore the effects of a cognitive rehabilitation program comprising a combination of cognitive and physical exercises, as well as group sessions to improve cognitive performance, emotional state, and cognitive reserve index. METHOD: Fifty patients with MS were subdivided into 2 groups: the control group, which performed aerobic exercise (n=25), and the experimental group (n=25), which participated in the integrated cognitive rehabilitation program (ICRP). All participants were evaluated 3 times (baseline, post-treatment, and long-term) with the Brief Repeatable Battery of Neuropsychological Tests, Cognitive Reserve Scale, Beck Depression Inventory, and a scale evaluating trait and state anxiety. RESULTS: Compared with the control group, patients in the experimental group showed improvements in cognitive function, with significant changes in measures of information processing speed, attention, memory, cognitive reserve index, and long-term mood. CONCLUSIONS: The ICRP was effective in improving cognitive and emotional function in MS, and increased the cognitive reserve index.

Cognition as a parameter in monitoring the effect of multiple sclerosis relapse treatment: A prospective controlled study.

BACKGROUND: Cognitive evaluation was considered to be very important in the relapse period, on the basis of the presence of isolated cognitive attacks and the necessity of monitoring the patient both physically and cognitively. MATERIALS AND METHODS: People with MS (pwMS) who were hospitalized during relapse were included in the study. All MS patients were evaluated by the neurologist with Expanded Disability Status Scale (EDSS), The 9 Hole Peg Test (9HPT) and the Timed 25-Foot Walk Test (T25-FWT). Additionally, all participants were examined cognitively with the Turkish version of the Brief International Cognitive Assessment for MS (BICAMS) battery. Also, schedules were indicated as during relapse before the treatment (pre-treatment) and the first month after relapse (1-month follow-up). RESULTS: A total of 140 MS patients (mean age; 34.98±10.09, mean disease duration; 6.05±5.29 years) and 86 healthy controls (mean age; 36.94±10.83) were included to the present study. The mean EDSS scores in pre-treatment in MS patients was 2.74±1.14 and decreased significantly in the 1-month follow-up (1.74±1.24; p<0.001). The mean SDMT score was lower by 8.76 points in MS patients than in HCs) in pre-treatment and 7.66 points in 1-month follow-up (p<0.001). The mean SDMT scores of all participants increased with measurement time gradually (p<0.001). CONCLUSION: In this study, it was detected which cognitive domains were affected after relapse treatment and cognitive changes in pwMS during relapse and remission periods compared to the healthy controls. All three BICAMS test scores significantly increased in one-month follow-up than the pre-treatment period. The results showed that CVLT-II and BVMT-R scores improved more in pwMS than in HCs, and also SDMT scores of pwMS showed a trend of increase, but was not a significant improvement.

The use of event-related potentials in the investigation of cognitive performance in people with Multiple Sclerosis: Systematic review.

A biomarker of cognition in Multiple Sclerosis (MS) that is independent from the response of people with MS (PwMS) to test questions would provide a more holistic assessment of cognitive decline. One suggested method involves event-related potentials (ERPs). This systematic review tried to answer five questions about the use of ERPs in distinguishing PwMS from controls: which stimulus modality, which experimental paradigm, which electrodes, and which ERP components are most discriminatory, and whether amplitude or latency is a better measure. Our results show larger pooled effect sizes for visual stimuli than auditory stimuli, and larger pooled effect sizes for latency measurements than amplitude measurements. We observed great heterogeneity in methods and suggest that future research would benefit from more uniformity in methods and that results should be reported for the individual subtypes of PwMS. With more standardised methods, ERPs have the potential to be developed into a clinical tool in MS.

Fear of falling and common symptoms of multiple sclerosis: Physical function, cognition, fatigue, depression, and sleep - A systematic review.

BACKGROUND: Fear of falling (FOF) is a common concern among persons with multiple sclerosis (MS) and affects the performance of their daily living activities. Falls may result in FOF, leading to worsening of symptoms of MS, physical deconditioning, and exposure to future falls. This may trigger a vicious cycle between FOF and falls. A better understanding of the relationship between FOF and symptoms of MS may be helpful to develop a conceptual model to guide fall prevention interventions. OBJECTIVE: To synthesize the correlational and predictive relationships between FOF and common symptoms of MS. METHODS: Databases including PubMed, Embase, Web of Science, Scopus, CINHAL, PsycINFO, and SPORTDiscuss were searched from inception to October 2023. Studies examining correlations and/or predictions between FOF and common MS symptoms that include measures of gait, postural control, fatigue, cognition, pain, sleep, depression, and anxiety were identified by two independent reviewers. Both reviewers also conducted the methodological quality assessment of the included studies. RESULTS: Twenty-three studies with a total of 2819 participants were included in the review. Correlational findings indicated that increased FOF was significantly associated with greater walking deficits (lower gait speed, smaller steps), reduced mobility, and poorer balance. Increased FOF was also significantly correlated with higher cognitive impairments, more fatigue, sleep disturbances, and depression. Decreased gait parameters, reduced balance, lower physical functions, cognitive impairments, and sleep deficits were found as significant predictors of increased FOF. CONCLUSION: Evidence indicates significant correlational and bidirectional predictive relationships exist between FOF and common MS symptoms. A comprehensive conceptual framework accounting for the interaction between FOF and MS symptoms is needed to develop effective falls prevention strategies.

Cross-cultural validity and reliability of the comprehensive assessment of acceptance and commitment therapy processes (CompACT) in people with multiple sclerosis.

PURPOSE: The Comprehensive assessment of Acceptance and Commitment Therapy (CompACT) is a 23-item questionnaire measuring psychological flexibility, a quality of life protective factor. An 18-item version was recently produced. We assessed validity and reliability of CompACT, and equivalence of paper and electronic (eCompACT) versions in people with multiple sclerosis (PwMS) in Italy, Germany and Spain. METHODS: We used confirmatory factor analysis and assessed CompACT-23 and CompACT-18 measurement invariance between the three language versions. We assessed construct validity (Spearman's correlations) and internal consistency (Cronbach's alpha). Test-retest reliability (intraclass correlation coefficient, ICC) and equivalence of paper and eCompACT (ICC and linear regression model for repeated measures) were assessed in subsamples of PwMS. RESULTS: A total of 725 PwMS completed the study. The three-factor structure of the CompACT-23 showed poor fit (RMSEA 0.07; CFI 0.82; SRMR 0.08), while the fit of the CompACT-18 was good (RMSEA 0.05; CFI 0.93; SRMR 0.05). Configural and partial metric invariance were confirmed, as well as partial scalar invariance (reached when five items were allowed to vary freely). The CompACT-18 showed good internal consistency (all alpha ≥ 0.78); and test-retest reliability (all ICCs ≥ 0.86). Equivalence between paper and eCompACT was excellent (all ICCs ≥ 0.86), with no mode, order, or interaction effects. CONCLUSION: Results support using the refined CompACT-18 as a three-factor measure of psychological flexibility in PwMS. Paper and eCompACT-18 versions are equivalent. CompACT-18 can be used cross-culturally, but sub-optimal scalar invariance suggests that direct comparison between the three language versions should be interpreted with caution.

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).

Domain-specific cognitive impairment in multiple sclerosis: A systematic review and meta-analysis.

OBJECTIVE: Methods of cognitive measurements in multiple sclerosis (MS) are not standardized. We aimed to identify the prevalence of cognitive domain-specific impairment (DSI) in MS by using subtests of the Brief Repeatable Battery of Neuropsychological Tests (BRB-N) with analyzing different cutoff values. METHODS: The systematic review and meta-analysis were registered on PROSPERO (ID: CRD42021287004). The systematic literature search was performed via PubMed, Embase, and CENTRAL on 24 October 2021. Inclusion criteria were adults of different MS subtypes (CIS, RRMS, PPMS, and SPMS) with the condition of distinct DSI measured by BRB-N. Pediatric MS, computerized versions of BRB-N, and patients receiving steroids were excluded. Primary outcome was pooled prevalence rates of impaired patients within each cutoff and MS subtype, with 95% confidence interval, I-squared statistics for heterogeneity, and chi-squared test for subgroup differences. Risk of bias was assessed using the "JBI Quality Assessment Tool for Prevalence Studies." RESULTS: In 48 eligible observational studies (n = 3431 patients), the three most prevalent thresholds were the 2.0 SD and 1.5 SD below the mean of normative values, and the score below the fifth percentile of the normative values. A progressively increasing worsening of the overall DSI was observed from CIS, moving toward RRMS, PPMS, and SPMS. INTERPRETATION: Cognitive impairment is observed in all MS phenotypes, with varying degrees. Due to several potential influencing factors, our comprehensive literature review has not revealed consistent findings, and we, therefore, recommend considering a more sophisticated, "individual referencing" approach, acknowledging the diverse clinical and sociodemographic characteristics among populations and disparities in cognitive testing.

Utility of the Brief Assessment of Cognitive Health (BACH) computerized screening tool in identifying MS-related cognitive impairment.

BACKGROUND: Current guidelines recommend that individuals with MS are screened annually for processing speed deficits, often using the Symbol Digit Modalities Test (SDMT). However, given the heterogeneity of cognitive deficits in individuals with MS, other screening measures that assess a range of cognitive domains are necessary. The current cross-sectional study aimed to examine the ability of the computerized, self-administered Brief Assessment of Cognitive Health (BACH) screening measure to detect the presence of cognitive impairment in adults with MS as determined by performance on a standard neuropsychological test battery. METHODS: Seventy-two individuals with MS completed the BACH and a comprehensive neuropsychological test battery. Receiver operating characteristic (ROC) analyses were conducted to investigate the ability of the BACH to identify cognitively impaired and cognitively intact individuals. ROC analyses were also conducted to compare the ability of the SDMT to discriminate between cognitively intact and cognitively impaired groups as a comparison with the BACH. RESULTS: Cognitive impairment was observed in 56 % of the sample. The BACH showed acceptable ability to discriminate between cognitively intact and cognitively impaired groups (AUC = 0.78). Additionally, the BACH was able to adequately predict cognitive impairment in domains other than processing speed (AUC = 0.71). The SDMT also demonstrated adequate utility in identifying individuals with cognitive impairment (AUC = 0.73); however, the SDMT was not able to adequately predict cognitive impairment in domains other than processing speed (AUC = 0.56). CONCLUSION: The BACH showed adequate ability to detect cognitive impairment in individuals with MS. The BACH was able to identify impairments across various assessed cognitive domains, including individuals with and without processing speed deficits.

Physical activity together for MS (PAT-MS): Secondary outcomes of a randomized controlled feasibility trial.

BACKGROUND: Care partners provide essential care to those with multiple sclerosis (MS). Dyadic interventions promoting health behaviours have wide-reaching benefits for individuals with MS and their care partners. However, behavioural interventions to promote physical activity in patient-caregiver dyads have yet to be explored in an MS-specific context. This study examined the secondary outcomes of the "Physical Activity Together for Multiple Sclerosis (PAT-MS)" intervention, including dyadic adjustment, caregiving tasks, caregiver quality of life, coping, and MS impact in MS dyads. METHODS: A randomized controlled feasibility trial of the 12-week behavioural PAT-MS intervention. The Dyadic Adjustment Scale, Caregiving Tasks in MS Scale, Caregiver Quality of Life in MS Scale, Coping with MS Caregiving Inventory, and MS Impact Scale measured secondary outcomes of interest. Mixed-model ANOVAs were used to test changes in variables between groups (PAT-MS vs wait-list control) over time. RESULTS: 20 participants, including 10 people with MS (51.4 ± 10.1 years old; median patient-determined disease steps (PDDS) score= 4, IQR= 1.25) and 10 care partners (48.5 ± 12.1 years old) were recruited and randomized. There was no statistically significant effect of the intervention on any of the secondary outcomes (p= 0.67-1.00). However, large effect sizes and condition-by-time interaction effects indicated improvement in dyadic adjustment (d= 1.03, ηp2= 0.45), the criticism-coercion coping subscale (d= -0.93, ηp2= 0.49), and caregiving tasks (d= 1.05, ηp2= 0.52), specifically within psycho-emotional (d= 1.47, ηp2= 0.38) and socio-practical (d= 1.10, ηp2 =0.37) sub-domains of caregiving tasks after the PAT-MS intervention compared to the wait-list condition. CONCLUSION: While this pilot feasibility study was not powered based on the secondary outcomes herein, our findings indicate improvement in dyadic adjustment and emotional and social caregiving tasks, with reduced reliance on criticism-coercion coping in the PAT-MS group compared to controls following the intervention. Findings indicate that PAT-MS may improve dyadic psychosocial well-being of people with moderate-to-severe MS and their care partners, and this should be examined next in a fully-powered study.

Don't be late! Timely identification of cognitive impairment in people with multiple sclerosis: a study protocol.

BACKGROUND: Cognitive impairment occurs in up to 65% of people with multiple sclerosis (PwMS), negatively affecting daily functioning and health-related quality of life. In general, neuropsychological testing is not part of standard MS-care due to insufficient time and trained personnel. Consequently, a baseline assessment of cognitive functioning is often lacking, hampering early identification of cognitive decline and change within a person over time. To assess cognitive functioning in PwMS in a time-efficient manner, a BICAMS-based self-explanatory digital screening tool called the Multiple Screener©, has recently been developed. The aim of the current study is to validate the Multiple Screener© in a representative sample of PwMS in the Netherlands. Additionally, we aim to investigate how cognitive functioning is related to psychological factors, and both work and societal participation. METHODS: In this cross-sectional multicentre study, 750 PwMS (aged 18-67 years) are included. To obtain a representative sample, PwMS are recruited via 12 hospitals across the Netherlands. They undergo assessment with the Minimal Assessment of Cognitive Functioning in MS (MACFIMS; reference-standard) and the Multiple Screener©. Sensitivity, specificity, and predictive values for identifying (mild) cognitive impairment are determined in a subset of 300 participants. In a second step, the identified cut-off values are tested in an independent subset of at least 150 PwMS. Moreover, test-retest reliability for the Multiple Screener© is determined in 30 PwMS. Information on psychological and work-related factors is assessed with questionnaires. DISCUSSION: Validating the Multiple Screener© in PwMS and investigating cognition and its determinants will further facilitate early identification and adequate monitoring of cognitive decline in PwMS.

Internet-delivered lifestyle physical activity intervention for cognitive processing speed in multiple sclerosis.

BACKGROUND: We propose a randomized controlled trial(RCT) of a Social Cognitive Theory-based(SCT), Internet-delivered behavioral intervention targeting lifestyle physical activity(LPA) for yielding improvements in cognitive processing speed(CPS), learning and memory(L/M), symptoms, and quality of life(QOL) among persons with mild multiple sclerosis(MS)-related ambulatory impairment who have impaired CPS. METHODS/DESIGN: The study involves a Phase-II, parallel group, RCT design. Participants with MS(N = 300) will be randomly assigned on an equal basis(1:1) into behavioral intervention(n = 150) or attention and social contact control(n = 150) conditions. The conditions will be administered over 6-months by trained behavior coaches who will be uninvolved in screening, recruitment, random assignment, and outcome assessment. We will collect outcome data remotely every 6-months over the 12-month period(baseline, immediate follow-up, and 6-month follow-up) using a treatment blinded assessor. The primary outcome is the raw, oral Symbol Digit Modalities Test as a neuropsychological measure of CPS. The secondary outcomes include the California Verbal Learning Test-II as an objective measure of L/M, and patient-reported outcomes of fatigue, depressive symptoms, anxiety, pain, and QOL. The tertiary outcome is accelerometry as an objective, device-based measure of steps/day for generating a minimal clinically important difference(MCID) value that guides the prescription of LPA for improving CPS in clinical practice. The primary data analyses will involve intent-to-treat principles, and mixed-effects models and logistic regression. DISCUSSION: If successful, the proposed study will provide Class I evidence for the efficacy of a theory-based, Internet-delivered behavioral intervention focusing on LPA for improving CPS and mitigating its negative impact on other outcomes in persons with MS. CLINICALTRIALS: gov: NCT04518657.

Validation of the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) in individuals with multiple sclerosis from Mexico.

BACKGROUND: Cognitive impairment is observed in 43-70 % of Multiple sclerosis (MS) patients. One of the most widely used batteries for cognitive assessment in this population is the Brief International Cognitive Assessment for MS (BICAMS). The objective of this study was to validate and assess the reliability of the BICAMS in a Mexican population with MS and to obtain and provide regression-based norms. METHODS: One hundred healthy controls (HCs) and 100 patients with multiple sclerosis participated in the present study, and groups were matched for age, years of education and sex. Subjects completed all three tests of the BICAMS. Test-retest measures were obtained from 30 patients to test reliability. RESULTS: The sample´s average age was 43.39 ± 6.03 years old, and the average years of education was 12.55 ± 2.52 years. Approximately 63 % of the participants were female. The groups did not differ in age, years of education, or sex. The MS group performed significantly worse than the HCs group on all three neuropsychological tests. A significant difference was observed for the SDMT (t = 10.166; p=<0.001), CVLT-II (t = 10.949; p=<0.001), and BVMT-R (t = 2.636; p = 0.009). For all comparisons, the effect size (d) for each test was calculated as follows: SDMT= 0.58 and CVLT-II= 0.61. The test-retest coefficients for each test were as follows: SDMT: r = 0.95; CVLT-II: r = 0.84; and BVMT-R = 0.81. CONCLUSION: The BICAMS can provide information on cognitive impairment in MS patients, and this information can be used by neuropsychologists for cognitive rehabilitation in different domains.

A collaborative approach to designing an online nutrition education program for people with multiple sclerosis.

PURPOSE: People with multiple sclerosis (pwMS) want disease-specific dietary advice to reduce the confusion around diet. This study used co-design principles to develop an online nutrition education program for pwMS. METHODS: Mixed-methods (multiphase sequential design). Phase 1: online survey (n = 114 pwMS) to explore preferred content and characteristics of a nutrition program and develop a draft program. Phase 2: feedback on the draft program from stakeholders (two meetings; n = 10 pwMS and multiple sclerosis (MS) health professionals) and pwMS (two workshops; n = 6) to produce a full program prototype. Phase 3: cognitive interviews (n = 8 pwMS plus 1 spouse) to explore acceptability and ease of comprehension of one module of the program, analysed using deductive content analysis. RESULTS: Preferred topics were included in the program, which were further developed with consumer feedback. Cognitive interviews produced four themes: (1) positive and targeted messaging to motivate behaviour change; (2) "not enough evidence" is not good enough; (3) expert advice builds in credibility; and (4) engaging and appropriate online design elements are crucial. CONCLUSIONS: Positive language appears to improve motivation to make healthy dietary changes and engagement with evidence-based nutrition resources. To ensure acceptability, health professionals can use co-design to engage consumers when developing resources for pwMS.IMPLICATIONS FOR REHABILITATIONCo-designed nutrition education programs can help people achieve high-quality diets in line with recommendations, but very few programs exist for people with multiple sclerosis (MS), and none were co-designedThe participatory research in this study was instrumental in ensuring that important information regarding program acceptability was identifiedCo-design can ensure that the language is appropriate for the target audience, and positive language appeared to improve motivation in people with MS to engage with the online nutrition education programWhere practical and feasible, health professionals should collaborate with MS consumers when developing resources, and use positive, empowering language.

Social cognitive disruptions in multiple sclerosis: The role of executive (dys)function.

OBJECTIVE: Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system, resulting in a range of potential motor and cognitive impairments. The latter can affect both executive functions that orchestrate general goal-directed behavior and social cognitive processes that support our ability to interact with others and maintain healthy interpersonal relationships. Despite a long history of research into the cognitive symptoms of MS, it remains uncertain if social cognitive disruptions occur independently of, or reflect underlying disturbances to, more foundational executive functions. The present preregistered study investigated this directly. METHOD: Employing an experimental design, we administered a battery of computerized tasks online to a large sample comprising 134 individuals with MS and 134 age- and sex-matched healthy controls (HCs). Three tasks measured elements of executive function (working memory, response inhibition, and switching) and two assessed components of social cognition disrupted most commonly in MS (emotion perception and theory of mind). RESULTS: Individuals with MS exhibited poorer working memory (d = .31), response inhibition (d = -.26), emotion perception (d = .32), and theory of mind (d = .35) compared with matched HCs. Furthermore, exploratory mediation analyses revealed that working memory performance accounted for approximately 20% of the group differences in both measures of social cognition. CONCLUSIONS: Disruptions to working memory appear to serve as one of the mechanisms underpinning disturbances to social cognition in MS. Future research should examine if the benefits of cognitive rehabilitation programs that incorporate working memory training transfer to these social cognitive processes. (PsycInfo Database Record (c) 2024 APA, all rights reserved).