Cognitive impairment and its impact on employment: A qualitative interview-based study involving healthcare professionals and people living with multiple sclerosis.

BACKGROUND: Cognitive impairment can considerably impact the work life of people who have multiple sclerosis (MS). Cognitive symptoms are associated with an increased likelihood of unemployment, changes in employment and decreased working hours. This qualitative interview-based study aims to gather real-word experiences and perspectives from both people living with MS and healthcare professionals, to explore how cognitive symptoms are experienced in the workplace, how their impact is addressed, and what can be done to support people in managing and minimizing this impact on employment. METHODS: Semi-structured, one-to-one interviews were conducted with people living with MS who experience cognitive symptoms, and with healthcare professionals working in MS care. Participants were recruited from a healthcare market research agency based in the United States. The data obtained from the interviews were subsequently analysed using a Grounded Theory method, in order to identify the core themes that form the basis of this paper. RESULTS: A total of 20 participants (n = 10 people living with MS; n = 10 healthcare professionals) from the United States were interviewed. Overall, 9 themes were identified from the raw data, which were grouped into three core themes describing the perspectives and experiences reported by both people living with MS and healthcare professionals: (1) The implications of cognitive symptoms on work; (2) Challenges in addressing cognitive impairment and its impact on work in MS care; (3) Strategies and support for managing the impact of cognitive symptoms. CONCLUSION: The real-world insights of PwMS and HCPs gained from this qualitative study show that a multi-faceted approach to addressing cognitive impairment and its impact on the employment of PwMS is required. Workplace adjustments can range from self-implemented changes to changes put in place by employers to accommodate the various ways in which cognitive symptoms may impact a person's work. This study provides valuable information on how people living with MS can be affected by cognitive symptoms in the context of their employment; furthermore, that preparing early when possible and maintaining a proactive approach to managing their impacts on work are important for maintaining a good quality of life.

Exploring the relationship between manual dexterity and cognition in people with multiple sclerosis: 9-hole peg and multiple cognitive functions.

AIM AND RATIONALE: Problems with manual dexterity and cognition impact the everyday performance of people with multiple sclerosis (PwMS). Accumulated findings point to the relationship between deficits in manual dexterity and auditory domains of cognition with a lack of evidence on visuospatial and verbal aspects of cognitive functioning. Therefore, this study explores the relationship between manual dexterity and cognition in a cohort of PwMS. METHOD: This cross-sectional study collected data from 63 PwMS aged 22 to 55 through a convenient sampling method. Participants were diagnosed with relapsing-remitting multiple sclerosis (RRMS). Cognition was measured using a multi-domain computerized cognitive testing, NeuroTrax, and manual dexterity was measured using a 9-hole peg assessment. Spearman correlation was used to identify the correlation among cognition subtests as well as with manual dexterity. Linear regression analysis was also conducted to identify whether manual dexterity predicts cognitive functioning. RESULTS: A significant negative correlation was found between 9-hole peg scores and global cognitive scores (GCS), r = -0.34, p = 006. The manual dexterity scores were also shown to predict GCS, R2= 0.165, p = 0.001. CONCLUSION: Manual dexterity was found to not only predict cognitive dysfunction but was also associated with multiple cognitive domains. Understanding the relationship between manual dexterity and cognition and the inferred progression of deficits can assist clinicians to provide interventions at earlier stages of disease progression to potentially increase daily functioning and quality of life (QoL).

Cognitive Impairment in Multiple Sclerosis: Past, Present, and Future.

Cognitive impairment in multiple sclerosis (MS) is common and can have negative effects on quality of life. The clinical presentation can be more subtle and insidious. Thus, cognitive impairment is often underrecognized by both persons with MS (PwMS) and clinicians, leading to underestimation disability due to MS. Recent evidence supports that relapses affect cognition in a similar pattern to other physical relapse symptoms and may be the only symptom of a relapse. Regular screening using validated tests for PwMS will improve the care provided and quality of life of PwMS.

De-escalation of Disease-Modifying Therapy for People with Multiple Sclerosis Due to Safety Considerations: Characterizing 1-Year Outcomes in 25 People Who Switched from Ocrelizumab to Diroximel Fumarate.

INTRODUCTION: Switching disease-modifying therapy (DMT) may be considered for relapsing-remitting multiple sclerosis (RRMS) if a patient's current therapy is no longer optimal. This was particularly important during the recent COVID-19 pandemic because of considerations around immune deficiency and impaired vaccine response associated with B cell-depleting DMTs. This real-world, single-center study aimed to evaluate change or decline in functional ability and overall disease stability in people with RRMS who were switched from B cell-depleting ocrelizumab (OCRE) to diroximel fumarate (DRF) because of safety concern related to the COVID-19 pandemic. METHODS: Adults with RRMS were included if they had been clinically stable for ≥ 1 year on OCRE. Data collected at baseline and 1 year post switch included relapse rate, magnetic resonance imaging (MRI), blood work for assessment of peripheral immune parameters, the Cognitive Assessment Battery (CAB), optical coherence tomography (OCT), and patient-reported outcomes (PROs). RESULTS: Participants (N = 25) had a mean (SD) age of 52 (9) years, and a mean (SD) duration of 26 (8) months' treatment with OCRE before the switch to DRF. Median washout duration since the last OCRE infusion was 7 months (range 4-18 months). No participants relapsed on DRF during follow-up, and all remained persistent on DRF after 1 year. There were no significant changes in peripheral immune parameters, other than an increase in the percentage of CD19+ cells 1 year after switching (p < 0.05). Similarly, there were no significant changes in CAB, OCT, and PROs. CONCLUSION: These preliminary findings suggest that transition to DRF from OCRE may be an effective treatment option for people with RRMS who are clinically stable but may need to switch for reasons unrelated to effectiveness. Longer follow-up times on larger samples are needed to confirm these observations.

Self-reported cognitive function mediates the relationship between employment status and cognitive functioning in persons with multiple sclerosis.

BACKGROUND: Cognitive impairment (CI) is common in people with MS (PwMS). Evidence is lacking for the self-reported CI's mediation effect on employment status and objective cognitive performance. Self-reported CI was found to be unreliable and seemed to be more associated with depression rather than formal cognitive performance. We hypothesized that the link between subjective and objective assessments of cognitive functions, mood, and employment status may be more complex in PwMS than previously reported. OBJECTIVE: The aims of this study are the following: (Romero-Pinel et al., 2022) to determine whether employment status could affect performance in cognitive function testing and (Rao et al., 1991) whether their relationship may be mediated by self-reported CI; and (Deluca et al., 2013) to determine whether self-reported depression interacts with self-reported CI in influencing performance in various cognitive domains in PwMS. METHODOLOGY: A retrospective study was performed involving PwMS who completed the self-report Multiple Sclerosis Neuropsychological Questionnaire (MSNQ), Hospital Anxiety and Depression Scale-depression scale (HADS-D), Minimal Assessment of Cognitive Function in MS (MACFIMS) and had data regarding employment status. Included PwMS were classified as employed or unemployed. A structural equation modeling (SEM) approach was taken due to the advantage of examining multiple cognitive outcomes simultaneously while accounting for shared associations. First, a latent factor of memory and executive functioning modeled the error-free associations between both factors and a processing speed task (SDMT). Next, the model tested for the indirect effect of self-reported cognition (MSNQ) on employment status differences in each outcome (memory, speed, and executive functioning). Finally, we tested interactions between MSNQ and HADS-D on each of the outcomes. RESULTS: We included 590 PwMS: 72.5% female, mean age 44.2 years (SD = 10.5), mean disease duration 8.6 years (SD 9.0). The majority (n = 455, 77.1%) had relapsing MS; 357 (60.5%) were employed. About half (n = 301, 51%) did not report CI on the MSNQ; of those, 213 (70.8%) were employed. The mean MSNQ for employed PwMS was 24.5 (SD = 10.7) and 29.8 (SD = 11.2) for unemployed PwMS. Employed PwMS had significantly better memory (ß = .16, p < .05), executive functioning (ß = .25, p < .05), and processing speed (ß = .22, p < .05). MSNQ partially indirectly mediated the effect of employment status on memory (Δß = .03, p < .05) and executive functioning (Δß = .03, p < .05) and processing speed (Δß = .04, p < .05), indicating that self-report CI partially explains the influence of employment status on these cognitive domains. The association between MSNQ with both memory and executive functioning was moderated by depression, meaning that in PwMS with high HADS-D scores, MSNQ was more strongly related to worse memory and executive functioning. The final model was an acceptable fit to the data (χ2(87) = 465.07, p < .05; CFI = .90, RMSEA = .08, 90% CI [.06, .09], SRMR = .05) explaining 41.20%, 38.50% and 33.40% of the variability in memory, executive functioning, and processing speed, respectively. CONCLUSION: Self-reported CI partially explains the associations between employment status and objective cognitive assessment in PwMS. Depression may moderate the relationship between self-reported cognitive assessment and objective cognitive performance. Thus, employment status and mood may guide the interpretation of self-reported CI.

Thalamic atrophy and dysconnectivity are associated with cognitive impairment in a multi-center, clinical routine, real-word study of people with relapsing-remitting multiple sclerosis.

BACKGROUND: Prior research has established a link between thalamic pathology and cognitive impairment (CI) in people with multiple sclerosis (pwMS). However, the translation of these findings to pwMS in everyday clinical settings has been insufficient. OBJECTIVE: To assess which global and/or thalamic imaging biomarkers can be used to identify pwMS at risk for CI and cognitive worsening (CW) in a real-world setting. METHODS: This was an international, multi-center (11 centers), longitudinal, retrospective, real-word study of people with relapsing-remitting MS (pwRRMS). Brain MRI exams acquired at baseline and follow-up were collected. Cognitive status was evaluated using the Symbol Digit Modalities Test (SDMT). Thalamic volume (TV) measurement was performed on T2-FLAIR, as well as on T1-WI, when available. Thalamic dysconnectivity, T2-lesion volume (T2-LV), and volumes of gray matter (GM), whole brain (WB) and lateral ventricles (LVV) were also assessed. RESULTS: 332 pwMS were followed for an average of 2.8 years. At baseline, T2-LV, LVV, TV and thalamic dysconnectivity on T2-FLAIR (p < 0.016), and WB, GM and TV volumes on T1-WI (p < 0.039) were significantly worse in 90 (27.1 %) CI vs. 242 (62.9 %) non-CI pwRRMS. Greater SDMT decline over the follow-up was associated with lower baseline TV on T2-FLAIR (standardized ß = 0.203, p = 0.002) and greater thalamic dysconnectivity (standardized ß = -0.14, p = 0.028) in a linear regression model. CONCLUSIONS: PwRRMS with thalamic atrophy and worse thalamic dysconnectivity present more frequently with CI and experience greater CW over mid-term follow-up in a real-world setting.

Summary of Research: What Is the True Impact of Cognitive Impairment for People Living with Multiple Sclerosis? A Commentary of Symposium Discussions at the 2020 European Charcot Foundation.

Cognitive symptoms affect disease management and activities of daily living for people living with multiple sclerosis (MS). This summary of research article summarises previously published discussions ('What is the true impact of cognitive impairment for people living with multiple sclerosis? A commentary of symposium discussions at the 2020 European Charcot Foundation') from the 2020 European Charcot Foundation meeting between a patient expert living with MS, a neuropsychologist and a neurologist about the impact of cognitive impairment on people living with MS. These discussions highlighted that cognitive impairment may be under-prioritised in MS care and has a substantial impact on the daily lives of people living with MS. To address this, the panel recommended improved awareness about impaired cognition in MS, improved communication between people living with MS and healthcare professionals, and routine cognition screening. This will help improve management of cognitive symptoms to maximise the quality of life of people living with MS.

Experiences of people with multiple sclerosis and clinicians in using cognitive behavioural therapies for hidden symptoms: a systematic review and meta-aggregation.

PURPOSE: Cognitive behavioural therapies (CBTs) are a standard of care for treatment of many 'hidden symptoms' in people with MS (PwMS), such as stress, depression, and fatigue. However, these interventions can vary widely in formatting and may not be tailored for PwMS. To optimize CBTs for MS, understanding the experiences of PwMS and clinicians is essential. This systematic review and meta-aggregation synthesizes existing qualitative data on stakeholder perspectives of CBTs for PwMS. METHODS: Systematic searches across five major electronic databases were conducted. Studies reporting qualitative data were identified. Two reviewers performed screening, quality assessment, data extraction, and certainty of evidence assessments. Meta-aggregation was performed as per the Joanna Briggs Institute approach, entailing qualitative data extraction, developing categories, and synthesizing overall findings. RESULTS: Twenty-eight studies were included in this review, comprising data from 653 PwMS and 47 clinicians. In the meta-aggregation, 122 qualitative results were extracted and grouped into nine categories. Categories were then combined into six synthesized findings: (1) setting the context-life with MS, (2) reasons for participating in CBTs, (3) acceptability of and experiences with participating in CBTs, (4) perceived benefits of CBTs, (5) perceived challenges with CBTs, and (6) suggestions to improve CBTs for PwMS. CONCLUSIONS: A range of benefits including psychological, social, and lifestyle improvements were reported, but varied based on the design of the CBT intervention. Future CBT interventions should be tailored to participant needs, delivered in group settings, offer online options, and be delivered by a trained facilitator familiar with MS. Further exploration of the ideal CBT design for PwMS, as well as engagement with caregivers and clinicians treating MS, is warranted.

Predicting time to serologic diagnosis of AQP4+ NMOSD based on clinical factors and social determinants of health.

BACKGROUND: Early serologic diagnosis and initiation of targeted therapy are associated with better outcomes in aquaporin-4 IgG positive (AQP4+) neuromyelitis optica spectrum disorder (NMOSD). OBJECTIVE: To determine predictors of time to serologic diagnosis of AQP4+ NMOSD. METHODS: In CANOPTICS, a multi-centre, Canadian cohort study of NMOSD, we retrospectively evaluated time from the first clinical attack to first positive AQP4-IgG serology. We used a multivariable negative binomial regression model to evaluate possible predictors of time to diagnosis. RESULTS: We identified 129 participants with AQP4+ NMOSD from 7 centres. Diagnostic delay of >1 month was observed in 82 (63.6 %). Asian compared to European (White) ethnicity (IRR:0.40, 95 % CI:0.21-0.78), female sex (IRR:0.56, 95 % CI:0.32-0.99), later calendar year (IRR:0.84, 95 % CI:0.81-0.86), and hospitalization for the first attack (IRR:0.35, 95 % CI:0.20-0.62) were associated with shorter times to serologic diagnosis. We did not observe any overall effect of Afro-Caribbean ethnicity, but in exploratory analyses, Afro-Caribbean individuals with low income had longer times to diagnosis. CONCLUSION: More than 60 % of patients with NMOSD experienced delays to AQP4-IgG serologic diagnosis in this cohort. Given evidence of more adverse long-term outcomes in Afro-Caribbean individuals with NMOSD, intersectional effects of ethnicity and social determinants of health merit further study.

Peering further into the mind's eye: combining visual evoked potential and optical coherence tomography measures enhances insight into the variance in cognitive functioning in multiple sclerosis.

BACKGROUND: Spectral Optical Coherence Tomography (OCT) and Visual Evoked Potentials (VEPs) have both emerged as potentially useful biomarkers of cognitive decline in people with multiple sclerosis (PwMS). Their combined use may provide additional predictive value for identifying disease impact, progression, and remyelination capacity above-and-beyond what is captured using either approach alone. OBJECTIVE: We examined the relationship between OCT/VEP measures and cognitive functioning in 205 PwMS. OCT measures included Retinal Nerve Fiber Layer Volume (RNFLV), Papillo-Macular Bundle Volume (PBMV), and Macular Volume (MV). VEP measures included latency of the P100, and inter-ocular latency. Cognitive performance was evaluated across seven separate domains of performance, and for overall cognition, using the NeuroTrax computerized testing battery. RESULTS: Both OCT and VEP measures were significantly correlated with cognitive performance across several domains. Linear regression models that controlled for the influence of visual acuity revealed (1) that reduced MV was significantly predictive of poorer visual-spatial functioning, and (2) that delayed VEP latency was significantly predictive of performance in global cognitive functioning and visual-spatial functioning, after controlling for multiple comparisons. Among PwMS with normal visual acuity, PwMS with a combination of both relatively low MV and delayed VEP latency tended to have poorer performance in the domains of global, executive, and visual-spatial functioning compared to PwMS with both high MV and normal VEP latency. CONCLUSION: Approaches that combine the use of OCT and VEP measures can enhance insight into underlying factors that contribute to variance in cognitive functioning in PwMS.

The influence of personality in persons with MS.

BACKGROUND: Comprehending the influence of personality traits on functional outcomes in persons with Multiple Sclerosis (pwMS) can aid in tailoring interventions and support strategies. We explored how demographic variables and personality traits predicted current vocation, information processing speed, anxiety and depression symptoms, and disability level in pwMS. METHODS: We used a retrospective chart review on pwMS treated at the London (ON) MS Clinic, that assessed demographic data and personality traits. Participants were 384 (68.8 % females, mean age of 37.8, SD = 10.4) individuals with relapsing and primary progressive MS. We performed hierarchical linear regressions to predict outcomes while considering demographic variables and personality traits. RESULTS: Younger age, higher education, and conscientiousness were significant predictors for better information processing speed, current vocation, depression symptoms, and disability level. Neuroticism was positively associated with anxiety and depression symptoms, while extraversion was negatively associated with depression symptoms. Women showed higher anxiety symptoms, while men showed higher depression symptoms. CONCLUSION: Personality traits, such as neuroticism and conscientiousness, influence psychological outcomes in pwMS. Younger age and higher education are associated with better functional outcomes. Thus, when considering personality traits, future interventions should focus on those with higher neuroticism and lower scores on both extraversion and conscientiousness. Consideration of social support, coping strategies, and disease severity in future research may further enrich our understanding of MS outcomes.

Multiple sclerosis.

Multiple sclerosis remains one of the most common causes of neurological disability in the young adult population (aged 18-40 years). Novel pathophysiological findings underline the importance of the interaction between genetics and environment. Improvements in diagnostic criteria, harmonised guidelines for MRI, and globalised treatment recommendations have led to more accurate diagnosis and an earlier start of effective immunomodulatory treatment than previously. Understanding and capturing the long prodromal multiple sclerosis period would further improve diagnostic abilities and thus treatment initiation, eventually improving long-term disease outcomes. The large portfolio of currently available medications paved the way for personalised therapeutic strategies that will balance safety and effectiveness. Incorporation of cognitive interventions, lifestyle recommendations, and management of non-neurological comorbidities could further improve quality of life and outcomes. Future challenges include the development of medications that successfully target the neurodegenerative aspect of the disease and creation of sensitive imaging and fluid biomarkers that can effectively predict and monitor disease changes.

Establishing the consistency of a voice recognition symbol digit modalities test analogue.

BACKGROUND: We previously demonstrated the convergent validity of a fully automated voice recognition analogue of the Symbol Digit Modalities Test (VR-SDMT) for evaluating processing speed in people with multiple sclerosis (pwMS). OBJECTIVE/METHODS: We aimed to replicate these results in 54 pwMS and 18 healthy controls (HCs), demonstrating the VR-SDMT's reliability. RESULTS: Significant correlations were found between the VR-SDMT and the traditional oral SDMT in the multiple sclerosis (MS) (r = -0.771, p < 0.001) and HC (r = -0.785, p < 0.001) groups. CONCLUSION: Taken collectively, our two studies demonstrate the reliability and validity of the VR-SDMT for assessing processing speed in pwMS.

Does multilingualism act as a protective factor (cognitive reserve) against cognitive impairment in multiple sclerosis?: A retrospective cohort study.

BACKGROUND: Cognitive impairment (CI) is common in multiple sclerosis (MS), affecting half of persons with MS (PwMS). Cognitive reserve has been associated with delaying the onset and slowing the progression of CI in PwMS. Multilingualism has been demonstrated to be a protective factor against CI in Alzheimer's disease (AD) but has never been studied in PwMS. OBJECTIVE: To explore if multilingualism is a protective factor against CI in PwMS. METHODS: This is a retrospective cohort study of PwMS aged 18-59, with a confirmed diagnosis of relapsing MS, fluent in English, who completed the Minimal Assessment of Cognitive Function in MS (MACFIMS) at the London (ON) MS Clinic. Any PwMS with a history of dementia or developmental delay, daily marijuana use, a major psychiatric disorder, or less than grade 9 education was excluded. We focused on the Brief Visuospatial Memory Test (BVMTR), immediate recall (-IR) and delayed recall (-DR) as it would be the least affected by language, as well as the Symbol Digit Modalities Test (SDMT), as information processing speed is the most commonly affected domain in PwMS. One-way ANOVA was used to compare raw scores on the BVMTR and SDMT between groups (uni- vs. multillingual), while chi-square was used to compare impairment on BVMTR and SDMT between groups. RESULTS: The cohort consisted of 678 subjects. The mean age was 39.7 (± 9.6) years with 501 (73.9 %) females (sex at birth), the mean duration of disease of 5.9 (± 6.9) years, and mean years of education was 13.9 (±2.2). The majority of subjects (563, 83 %) were unilingual and (115, 17 %) were multilingual; 102 subjects were bilingual and 13 subjects fluent in ≥ three languages. English was the first language was in most of subjects (614, 90.6 %). There was no significant difference on the BVMTR-IR scores (p = 0.189) or BVMTR-DR (p = 0.096) between groups. Similarly, there was no difference in the number of subjects impaired on the BVMTR-IR (X2 (1, N = 678) = 3.167, p = 0.057) or BVMT-DR between groups (X2 (1, N = 678) = 2.996, p = 0.083). Further, there was no significant difference on the SDMT (p = 0.506) between groups, or in number of subjects impaired on the SDMT between groups (X2 (1, N = 678) = 1.023, p = 0.312). CONCLUSION: This study shows that multilingualism does not have a protective effect against CI in PwMS and does not play a role in enriching the cognitive reserve, in contrast to studies in AD. This difference may be explained by a different underlying pathological mechanism in these diseases and warrants further study.

Detecting isolated cognitive relapses in persons with MS.

BACKGROUND: The existence of isolated cognitive relapses (ICRs) in persons with MS (PwMS) has been debated. OBJECTIVE: To examine relapses with decline on Symbol Digit Modalities Test (SDMT) but no change on Expanded Disability Status Scale (EDSS). METHODS: This 3-year prospective cohort study identified PwMS experiencing a relapse with decrease on SDMT. Participants with SDMT decline/stable EDSS were labeled "ICR," while those with a corresponding decrease on EDSS were classified "Relapse with Cognitive Decline (RCD)." Two definitions of SDMT decline were explored: (1) ⩾ 8 points, and (2) ⩾ 4 points. Logistic regression was used to analyze the relationship between ICR and RCD. RESULTS: The full cohort had 592 participants: 83 experienced relapses; 22 (26.5%) had an SDMT decrease of ⩾ 8 points; 14 (63.6%) met ICR criteria. Logistic regression (X2(1) = 5.112, p = 0.024) using demographics and disease characteristics explained 28.4% of the variance in ICR versus RCD. Only the MS Neuropsychological Questionnaire was associated with ICR (odds ratio (OR): 8.6; 95% confidence interval (CI): 1.1-16.4) 40 relapsing participants with SDMT decrease of ⩾ 4 points were identified: 26 (65%) had a stable EDSS (ICR). Logistic regression did not find any variable predictive of ICR. CONCLUSION: This prospective study demonstrates evidence of ICR in PwMS.

Diversity, Equity, and Inclusion in the Multiple Sclerosis Community: A Call to Action.

Many medical organizations have begun to confront the longstanding problem of inequalities in health care delivery and the undeniable effect of disparities on health outcomes. The Consortium of Multiple Sclerosis Centers (CMSC) recognizes that disparities affect the lives of many people with multiple sclerosis (MS) and acknowledges the need to address this as an organization. The CMSC recently (1) appointed a task force, (2) conducted a survey of its membership, (3) commissioned this review article and call to action, and (4) formulated a mission statement on diversity, equity, and inclusion (DEI), which was adopted by the CMSC's Board of Governors in March 2023. This paper summarizes recent literature on health care disparities in MS, particularly those relating to race/ethnicity, sexual orientation, and gender identity. It presents findings from CMSC's survey of members' awareness of DEI issues, the need for education and resources for MS care providers, and existing institutional policies on DEI in the members' practice settings. It also presents the task force's recommendations for next steps, which includes the goal of greater diversity in the MS workforce of the future. The CMSC will continue to revisit DEI policies and practices over time with the goal of motivating greater awareness, momentum, and positive changes within the MS community.