Persons With Multiple Sclerosis Research Articles

Patterns of prospective memory errors differ in persons with multiple sclerosis

ABSTRACT Introduction Prospective memory (PM) deficits have been documented in multiple sclerosis (MS). This study aimed to explore the specific types of errors made by persons with MS (PwMS), including differences between PwMS and healthy controls (HC) and PwMS who do and do not have impairments in processing speed and/or verbal learning and memory. Method PwMS (n = 111) and HC (n = 75) completed the Memory for Intentions Test (MIST), an objective measure of PM that has five types of errors that can be coded (PM failure, task substitution, loss of content, loss of time, and random errors). The number and types of PM errors were calculated for the overall MIST and six subscales, which break down performance by types of delay (2-Minute and 15-Minute), cue (Time and Event), and response (Verbal and Action). Impairment was defined as performing < 1.5 SD on either the Symbol Digit Modalities Test (SDMT) or Rey Auditory Verbal Learning Test (RAVLT). Bivariate analyses were used to examine group differences, with post-hoc pairwise comparisons with Bonferroni corrections. Results Nearly 93% of PwMS made at least one PM error, compared to 76% of HC (V = .24, p = .001). The most commonly made PM error by PwMS was loss of content errors (45.0%). PwMS made significantly more task substitution errors (26.4% vs. 7.6%, p < .001) and fewer loss of time errors (9.5% vs. 21.2%, p < .001) than HC. Impaired PwMS made more errors than non-impaired PwMS, specifically PM failures on time-based tasks. Conclusions PM errors are common in PwMS, particularly when there are longer delays and time-based cues. Not only do PwMS make more errors than demographically similar HC, but they exhibit different cognitive process failures.

492 Pain and falls among persons with multiple sclerosis.

OBJECTIVES/GOALS: Falls are very common among persons with multiple sclerosis (PwMS) due to the disabling symptoms associated with the disease. The relationship between pain and falls is underexplored. This study investigated the relationship between the facets of pain (intensity and interference) and falls in the context of co-occurring symptoms of MS. METHODS/STUDY POPULATION: This is a survey-based study that included 915 adults with MS. Participants provided data on demographics, clinical data, concerns about falling, symptom severity, and occurrence of falls in the past 6 months. Participants also completed the Patient Reported Outcome Measurement Information System (PROMIS) pain interference and pain intensity short forms. Pain interference and pain intensity were separately entered into univariate and multivariable logistic regression models developed to examine the associations between falls incidence and pain. Multivariable models were adjusted for age, sex, years since diagnosis, MS type, Patient Determined Disease Steps, MS status, concerns about falling, fatigue severity, PROMIS depression short form, and PROMIS physical function short form. RESULTS/ANTICIPATED RESULTS: Univariate regression analyses indicated that pain interference (OR = 1.05; 95% CI 1.03 to 1.06; p &lt; 0.01) and pain intensity (OR = 1.03; 95% CI 1.02 to 1.04; p &lt; 0.01) were both associated with falls. Only pain interference remained significantly associated with falls in multivariable regression analysis (OR = 1.02; 95% CI 1.00 to 1.05; p = 0.03). The model explained 25% of the variance in falls. Pain intensity was not associated with falls (OR = 0.98; 95% CI 0.95 to 1.01; p &gt; 0.05) in multivariable regression analysis. DISCUSSION/SIGNIFICANCE: The findings suggest that pain is associated with falls among PwMS. Interventions designed to reduce falls incidence among PwMS may consider the inclusion of pain management as an integral component of those programs.

Persons with multiple sclerosis older than 55years: an analysis from the German MS registry.

Persons with MS (PwMS) ≥ 55years are underrepresented in therapy studies leading to a lack of evidence. To study the subgroup of PwMS ≥ 55years in the German MS registry in comparison with PwMS < 55years. Endpoints of interest were the grade of disability, leading symptoms, clinical and magnetic resonance imaging activity, and use of disease modifying therapy. At the time of analysis, data from 40,428 PwMS were available for analysis. In PwMS aged ≥ 65 and PwMS aged ≥ 55 to 64years, compared with PwMS aged < 55years, the mean Expanded Disability Status Scale Scores were higher (5.3, 4.2 and 2.7, respectively), while the proportion of individuals with current use of disease modifying therapy was lower (42.6%, 60.9% and 76.7%, respectively). The older patient groups were more likely to be labeled with progressive MS and the frequency of occupational invalidity was high (38.8% in PwMS aged ≥ 55 to 64years). Gait disorder, fatigue, bladder dysfunction, and spasticity were among the leading symptoms in PwMS aged ≥ 55years. PwMS ≥ 55years have a high degree of disability, but a large proportion do not receive disease modifying therapy, exposing an unmet need.

The measurement of fatigability severity in individuals with multiple sclerosis and healthy controls

BackgroundMultiple Sclerosis (MS) is a chronic disease that substantially diminishes one's ability to undertake daily living activities. Fatigue has been reported by at least 80 % of persons with MS (PwMS). Yet, little is known concerning the quantification of fatigability using prolonged walking tests. ObjectivesTo compare fatigability severity measures using the 10-minute walk test for PwMS against age- and gender-matched healthy controls (HCs). MethodsParticipants included 53 ambulatory PwMS and 49 HCs. Perceived fatigability was measured by dividing a participant's change in self-reported tiredness by the number of meters walked. Performance fatigability was calculated by dividing the change in walking speed (at 2.5 and 10 min) by the total distance walked in meters. ResultsThere was a significant difference in perceived fatigability between PwMS and HCs (mean difference: 2.73 ± 0.83; p = 0.001) and in performance fatigability (mean difference: 0.24 ± 0.11; p = 0.01). Moreover, there were significant differences in speed and distance at all time points (p ≤ 0.05) between PwMS and HCs. ConclusionsPwMS have significant walking deficits as reflected by greater fatigability in both perceived and performance measures. These methods can enhance therapeutic strategies that improve the walking performances of PwMS.

Backwards walking speed reserve in persons with multiple sclerosis

BackgroundDecreased gait speed is common in persons with Multiple Sclerosis (PwMS) and has been associated with elevated fall risk. The walking speed reserve (WSR) indicates the ability to increase gait speed on demand and has previously been examined in PwMS. Backward walking is a sensitive measure of fall risk in PwMS; however, no studies have reported on the utility of backward walking speed reserve (BW-WSR) as a clinical assessment tool of functional mobility or fall risk in PwMS, nor have they associated this measure with cognition. Methods23 PwMS completed walking trials at their preferred walking speed (PWS) and maximal walking speed (MWS). Participants performed these walking trials in both the forward (FW) and backward direction (BW). The forward walking speed reserve (FW-WSR) was calculated as the difference between MWS and PWS in the forward direction, while the backward walking speed reserve (BW-WSR) was calculated as the difference between MWS and PWS in the back backward direction. Correlation analyses examined the relationship between the FW- and BW-WSR with clinical assessments of functional mobility (the timed up-and-go) as well as cognitive functioning (the Symbol Digit Modalities Test, the Brief Visuospatial Memory Test-Revised, the California Verbal Learning Test, and the Trail Making Test A and B). Correlations also examined the relationship between FW- and BW-WSR with prospective falls. ResultsA lower BW-WSR was associated with disease severity and poorer performance on clinical walking and balance assessment, as well as with decreased information processing speed and attentional performance. Interestingly, FW-WSR showed similar relations. Neither FW- or BW-WSR were associated with prospective risk in this small sample of PwMS. ConclusionThe BW-WSR did not offer a distinct advantage over other measures, such as the FW-WSR, PWS, or MWS, in the forward or backward direction. The selection of the most sensitive clinical measures of functional mobility and fall risk is crucial; our study holds valuable clinical implications for PwMS by providing novel insights into functional mobility assessments in PwMS.

Adaptation and validation of the Greek version of the Communication and Language Assessment questionnaire for persons with Multiple Sclerosis (CLAMS).

The aim of the present study was to validate the Communication and Language Assessment questionnaire for persons with Multiple Sclerosis (CLAMS) into the Greek language. 106 Persons with Multiple Sclerosis (PwMS) and 51 healthy controls (HCs) participated in this study. We evaluated patients' cognitive abilities with the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS). All PwMS completed the CLAMS and three additional questionnaires (Speech Pathology-Specific Questionnaire for persons with Multiple Sclerosis, SMS; Stroke and Aphasia Quality of Life Scale-39, SAQOL-39; the Beck Depression Inventory Fast Screen, BDI-FS), and all HCs filled in the CLAMS. The internal consistency of the CLAMS was excellent (a = 0.933) for the PwMS and a significant difference was found between PwMS and HCs for the total CLAMS score. Statistical analyses showed a significant positive correlation between the CLAMS and the other questionnaires (SMS, BDI, and SAQOL-39) and a statistically significant negative correlation between the CLAMS and the three subtests of the BICAMS (Symbol Digit Modalities Test, Greek Verbal Learning Test-II, and Brief Visuospatial Memory Test-Revised). There was no correlation between the CLAMS and participants' age, disease duration, and disease type. The Greek version of the CLAMS is a valid self-reported questionnaire for the evaluation of language and communication symptoms in PwMS.

Medically unexplained symptoms are common in women in tertiary neurological healthcare center: A survey cohort study of persons investigated for suspected multiple sclerosis.

A significant proportion of individuals with suspicious onset of multiple sclerosis (MS) does not fulfill the diagnostic criteria. Although some receive other diagnoses, many remain undiagnosed and lack healthcare follow-up. This study aimed to characterize persons with undetermined diagnosis (PwUD) through a questionnaire. Incident cases with suspected MS were consecutively admitted to a tertiary neurological healthcare center in a prospective cohort study. Those who remained undiagnosed after 40 months (mean, range 31-52) were considered PwUD. They completed a modified questionnaire, previously used in a population-based case-control study of incident MS cases. Their responses were compared with two control cohorts, persons with MS (PwMS) and healthy controls, randomly selected from national registries, matched by age, gender, and area of residence. Out of 271 patients with suspected MS onset, 72 (20.3%) were PwUD with a female majority (79%). The response rate was 83% and 39% reported persisting MS-like symptoms. Compared to controls (n=548) and PwMS (n=277), fewer PwUD were currently smoking (p=.4 and p=.03), consumed less alcohol (p=.04 and p=.01), and had children (p=.02 and p=.002). PwUD reported occurrence of other autoimmune disease in 29%, higher compared to PwMS and controls (p<.001 and p<.001). UD is common among persons investigated for suspected MS, in particular among female parents. Our data suggest that PwUD can be characterized as nonsmokers with low alcohol consumption and a higher prevalence of autoimmune disease, in particular thyroid disease.

Analysis of seroconversion following COVID-19 vaccination among multiple sclerosis patients treated with disease-modifying therapies in Poland.

The rapid spread of SARS-CoV-2 throughout the world has highlighted the importance of vaccinations to control the pandemic and to protect people at risk for severe disease courses. Disease-modifying therapies (DMT) in multiple sclerosis (MS), whether immunomodulatory or immunosuppressive, may affect the immune response. Therefore, the question arose as to whether these vaccinations would be effective. We planned a study to assess the immune response to SARS-CoV-2 vaccines by type of therapy. Participants were recruited from 14 Polish MS centres. The data was obtained by neurologists using a questionnaire. We collected data on 353 MS patients (269 females, 84 males) who received complete primary SARS-CoV-2 vaccination. All persons with MS (PwMS) were treated with disease-modifying therapies. 305 out of 353 PwMS (86.4%) were positive for IgG Abs against SARS-CoV-2 S domain S1 Ag after vaccination. A strong immune response was noted in 129 PwMS (36.5%). The rate of seroconversion after SARS-CoV-2 vaccination in PwMS who received immunomodulatory DMTs (interferon beta, glatiramer acetate, teriflunomide, dimethyl fumarate, natalizumab) was 91.5%, in PwMS receiving immune reconstruction therapy (alemtuzumab, cladribine) was 92%, and in immunosuppressive DMTs (fingolimod, ocrelizumab), the seroconversion rate was 59%. Our study shows that, in PwMS receiving immunomodulatory therapy, the immune response to vaccination is generally excellent. Even in immunosuppressive patients, seroconversion is satisfactory.

Drooling may be Associated with Dysphagia Symptoms in Multiple Sclerosis.

During the process of the multiple sclerosis (MS), persons with multiple sclerosis (PwMS) may experience drooling (sialorrhea) issues that are frequently disregarded. The exact cause of drooling in PwMS is poorly understood. This study aims to assess potential risk factors for drooling seen in PwMS. The study included 20 PwMS with drooling and 19 PwMS without drooling. The participants' sociodemographic data and clinical parameters were noted. To evaluate dysphagia, fatigue, and hypersalivation, the Dysphagia in Multiple Sclerosis Questionnaire(DYMUS), the Fatigue Severity Scale (FSS), and objective saliva flow rate measurement with cottons placed in Stensen ducts and under the tongue (swab test) were used, respectively. The study employed univariate and multivariate logistic regression models to identify the risk factors linked to drooling. Gender, age, disease duration, MS type, and Expanded Disability Status Scale scores did not differ between the two groups. There was a significant increase in the DYMUS and submandibular/sublingual (SM/SL) saliva flow rate values in PwMS with drooling (p = 0.009 and p = 0.019, respectively). However, in our study, hypersalivation was not observed in PwMS with or without drooling. In the univariate model, DYMUS, SM/SL saliva flow rate, and FSS were found to be risk factors for drooling in PwMS. But only DYMUS was shown to be a significant risk factor in the multivariate model obtained by the backward (Wald) elimination method (p = 0.023). Finally, our research is the first to demonstrate the relationship between drooling and the presence of dysphagia symptoms in PwMS. This is a very important study to determine the nature of drooling in PwMS. This finding shows that our study will serve as a reference for choosing the best method for drooling treatment.

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

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. 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. 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. 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).

Proteomic signatures of physical, cognitive, and imaging outcomes in multiple sclerosis.

A quantitative measurement of serum proteome biomarkers that would associate with disease progression endpoints can provide risk stratification for persons with multiple sclerosis (PwMS) and supplement the clinical decision-making process. In total, 202 PwMS were enrolled in a longitudinal study with measurements at two time points with an average follow-up time of 5.4 years. Clinical measures included the Expanded Disability Status Scale, Timed 25-foot Walk, 9-Hole Peg, and Symbol Digit Modalities Tests. Subjects underwent magnetic resonance imaging to determine the volumetric measures of the whole brain, gray matter, deep gray matter, and lateral ventricles. Serum samples were analyzed using a custom immunoassay panel on the Olink™ platform, and concentrations of 18 protein biomarkers were measured. Linear mixed-effects models and adjustment for multiple comparisons were performed. Subjects had a significant 55.6% increase in chemokine ligand 20 (9.7 pg/mL vs. 15.1 pg/mL, p < 0.001) and neurofilament light polypeptide (10.5 pg/mL vs. 11.5 pg/mL, p = 0.003) at the follow-up time point. Additional changes in CUB domain-containing protein 1, Contactin 2, Glial fibrillary acidic protein, Myelin oligodendrocyte glycoprotein, and Osteopontin were noted but did not survive multiple comparison correction. Worse clinical performance in the 9-HPT was associated with neurofilament light polypeptide (p = 0.001). Increases in several biomarker candidates were correlated with greater neurodegenerative changes as measured by different brain volumes. Multiple proteins, selected from a disease activity test that represent diverse biological pathways, are associated with physical, cognitive, and radiographic outcomes. Future studies should determine the utility of multiple protein assays in routine clinical care.

Physical Activity Moderates the Association Between Pain and Depressive Symptoms Among Persons with Multiple Sclerosis.

The present study examined physical activity as a possible moderator in the relationship between pain and depressive symptoms among persons with multiple sclerosis (PwMS). Fifty-three PwMS completed a comprehensive neuropsychological test battery and psychosocial questionnaires. Pain was operationalized as a composite of measures from the Brief Pain Inventory. Metabolic equivalents (METs) of energy expended during self-reported vigorous activity (VA), moderate activity (MA), and walking, as well as global physical activity which combined the three, were derived from the International Physical Activity Questionnaire-Short Form. Self-reported physical activity was measured using the Cognitive Health Questionnaire Exercise Scale. Regressions on depressive symptoms (Beck Depression Inventory-Fast Screen) examining both conceptualizations of physical activity, pain, and their interactions were explored. Regression analyses revealed that interactions between pain and each measure of global physical activity were significant (p = .01). Simple effects tests revealed that pain only influenced depressive symptoms in PwMS with low global physical activity METs (p < .001) and low overall self-reported physical activity (p < .001). The separate interactions between pain and METs during self-reported VA, MA, and walking on depressive symptoms were not significant. We found that global physical activity moderated the relationship between pain and depressive symptoms in MS. Specifically, pain influenced depressive symptoms in PwMS who engaged in less overall physical activity. These results highlight the importance of screening PwMS for pain and suggest that behavioral interventions aimed at increasing overall lifestyle physical activity may be useful in improving depressive outcomes in PwMS with pain.

Psychometric evaluation of the 5-item Medication Adherence Report Scale questionnaire in persons with multiple sclerosis.

The 5-item Medication Adherence Report Scale (MARS-5) is a reliable and valid questionnaire for evaluating adherence in patients with asthma, hypertension, and diabetes. Validity has not been determined in multiple sclerosis (MS). We aimed to establish criterion validity and reliability of the MARS-5 in persons with MS (PwMS). Our prospective study included PwMS on dimethyl fumarate (DMF). PwMS self-completed the MARS-5 on the same day before baseline and follow-up brain magnetic resonance imaging (MRI) 3 and 9 months after treatment initiation and were graded as highly and medium adherent upon the 24-cut-off score, established by receiver operator curve analysis. Health outcomes were represented by relapse occurrence from the 1st DMF dispense till follow-up brain MRI and radiological progression (new T2 MRI lesions and quantitative analysis) between baseline and follow-up MRI. Criterion validity was established by association with the Proportion of Days Covered (PDC), new T2 MRI lesions, and Beliefs in Medicines questionnaire (BMQ). The reliability evaluation included internal consistency and the test-retest method. We included 40 PwMS (age 37.6 ± 9.9 years, 75% women), 34 were treatment-naive. No relapses were seen during the follow-up period but quantitative MRI analysis showed new T2 lesions in 6 PwMS. The mean (SD) MARS-5 score was 23.1 (2.5), with 24 PwMS graded as highly adherent. The higher MARS-5 score was associated with higher PDC (b = 0.027, P<0.001, 95% CI: (0.0134-0.0403)) and lower medication concerns (b = -1.25, P<0.001, 95% CI: (-1.93-(-0,579)). Lower adherence was associated with increased number (P = 0.00148) and total volume of new T2 MRI lesions (P = 0.00149). The questionnaire showed acceptable internal consistency (Cronbach α = 0.72) and moderate test-retest reliability (r = 0.62, P < 0.0001, 95% CI: 0.33-0.79). The MARS-5 was found to be valid and reliable for estimating medication adherence and predicting medication concerns in persons with MS.

Assessing Free-Living Postural Sway in Persons With Multiple Sclerosis.

Postural instability is associated with disease status and fall risk in Persons with Multiple Sclerosis (PwMS). However, assessments of postural instability, known as postural sway, leverage force platforms or wearable accelerometers, and are most often conducted in laboratory environments and are thus not broadly accessible. Remote measures of postural sway captured during daily life may provide a more accessible alterative, but their ability to capture disease status and fall risk has not yet been established. We explored the utility of remote measures of postural sway in a sample of 33 PwMS. Remote measures of sway differed significantly from lab-based measures, but still demonstrated moderately strong associations with patient-reported measures of balance and mobility impairment. Machine learning models for predicting fall risk trained on lab data provided an Area Under Curve (AUC) of 0.79, while remote data only achieved an AUC of 0.51. Remote model performance improved to an AUC of 0.74 after a new, subject-specific k-means clustering approach was applied for identifying the remote data most appropriate for modelling. This cluster-based approach for analyzing remote data also strengthened associations with patient-reported measures, increasing their strength above those observed in the lab. This work introduces a new framework for analyzing data from remote patient monitoring technologies and demonstrates the promise of remote postural sway assessment for assessing fall risk and characterizing balance impairment in PwMS.

Improving the quality of life through vitamin D supplementation in people with multiple sclerosis: Pathobiological, immunologically based, A narrative review of the literature

An inadequate vitamin D nutritional status is associated with autoimmune diseases, heart disease, deadly types of cancer, neurological disorders and undesirable consequences in pregnancy, amongother things. In a nationally representative sample of adults in Australia on vitamin D (VitD) congestion in the general population, 20% of participants were verified to be Vit D deficient and 43% to have insufficient VitD levels [1]. It is therefore to be welcomed that in 2020 a guideline on VitD supplementation for medical use was created, taking into consideration the opinions of various global institutions [2]. For more than 15 years there have been reports that vitamin D (VitD) has an immunomodulatory function in multiple sclerosis (MS) [3] and that there is an association between low circulating serum levels of 25-hydroxyvitamin D [s25(OH)D] and an increase in inflammatory activity and impact on quality of life in persons with multiple sclerosis (PwMS) [4] [5]. Nevertheless, up to the present the "neurological community" has not been able to agree to start a daily add-on therapy using an easy to carry out, inexpensive and low-side effect vitamin D supplementation (VitD suppl. from the beginning of the diagnosed MS disease or the chronically isolated syndrome (CIS). In the last decade, there has been an accumulation of evidence of immunological and pathophysiological mechanisms that VitD positively influences the course of the disease and should become an eminent factor in therapy ([6]. For 13 years, neurologists in Sweden have been informing PwMS about the benefits of VitD-suppl. and given a recommendation for add-on therapy [7].

Sense of happiness in Polish patients with multiple sclerosis.

Happiness is crucial to patient well-being and their acceptance of their disease. The aim of this study was to assess the sense of happiness in persons with multiple sclerosis (PwMS), compare it to the level of happiness in patients with other neurological conditions, and determine which factors affect the sense of happiness in PwMS. Five hundred and eighty-nine PwMS and 145 control subjects (post-stroke patients with chronic pain syndromes and neuropathies) were included in the study. Due to the differences between the groups in terms of demographic variables, an adjusted group of PwMS (n = 145) was selected from the entire group of PwMS. All patients were assessed using the Oxford Happiness Questionnaire (OHQ), the Satisfaction with Life Scale (SLS), and the Family APGAR Questionnaire. Based on regression analysis, the study examined which variables affected the level of happiness in the groups. Analysis of the OHQ scores showed that PwMS had a lower sense of happiness compared to the control group in the overall score [113.21 (25-42) vs. 119.88 (25-49), respectively; p = 0.031] and the subscales (OHQ subscale 1 - 54.52 vs. 57.84, respectively; p = 0.027; subscale 2 - 35.61 vs. 37.67; respectively; p = 0.044). Based on linear regression analysis, life satisfaction (β = 0.40; p < 0.001), positive orientation (β = 0.32; p < 0.001), and primary education (β = 0.08; p = 0.009) were the most significant predictors of a higher level of happiness in PwMS. Similar results were found in the control group. The sense of happiness in PwMS was lower than in patients with other conditions. The most important factors influencing happiness included life satisfaction and positive orientation. Influencing these predictors should be the aim of psychological interventions, especially in patients with a reduced sense of happiness.

The effect of a structured running exercise intervention on non-exercise physical activity and sedentary behaviour in persons with mild Multiple Sclerosis and healthy controls

BackgroundExercise interventions fail to increase objective physical activity (PA) in persons with Multiple Sclerosis (PwMS), while they self-report higher exercise participation. This suggests that PwMS change their non-exercise PA (NEPA). We aimed to explore NEPA changes of PwMS and healthy controls (HC), and whether these constrain exercise adaptations.MethodsTwenty-nine mildly-disabled PwMS and 26 HC completed a 10-month home-based running program. A non-randomised controlled study design was used. The primary outcome was time in different NEPA intensities (light intensity PA [LIPA] and moderate-to-vigorous intensity PA [MVPA]) and in sedentary behaviour ([SB]; total and uninterrupted SB) at baseline (T1), after 5 (T2) and 10 (T3) months of exercise. Data were averaged over days with and without exercise sessions (EX and NONEX days). Secondary outcomes included patient-reported and physical exercise adaptations (fatigue, walking mobility, blood pressure, body composition and cardiorespiratory fitness).ResultsA significant reduction in non-exercise MVPA was observed from T1 to T2 (− 113 ± 31 min/week, p < 0.01) and from T1 to T3 (− 95 ± 26 min/week, p < 0.01) in PwMS, which approximately matched the weekly exercise duration at those time points. PwMS also increased their uninterrupted SB on NONEX days compared to EX days (+ 0.7 ± 0.3 h, p < 0.01). There were no changes in MVPA or SB of HC (group × time effect MVPA: p < 0.05; group × EX day effect uninterrupted SB: p < 0.01). Secondary outcomes improved similarly in both groups and were not associated with NEPA/SB changes.ConclusionsIn contrast to HC, PwMS significantly changed their NEPA and the pattern in which they accumulated SB in response to structured exercise. This might be a necessary behavioural compensation in order to adhere to the exercise intervention and did not constrain patient-reported and physical outcomes. Future research is warranted to unravel the underlying causes and to investigate the effects on other exercise adaptations, such as cardiometabolic health.Trial registration The present study was registered (December 10, 2019) at clinicaltrials.gov as NCT04191772

Impairment of daily occupations in multiple sclerosis: analysis of neuroimaging, general and social cognition, and reserve

BackgroundMultiple Sclerosis (MS) can impact performance of daily occupations in both relapsing-remitting (RRMS) and secondary-progressive (SPMS) clinical courses. Work force participation decreases with advancing physical disability but the influence of non-motor factors, neuroimaging, and reserve have been scarcely investigated. We aimed to evaluate MRI, clinical, and cognitive (social and general) factors associated with impairment in different daily occupations and address whether cognitive and brain reserve have a positive impact on the ability to maintain these activities. MethodsWe prospectively enrolled persons with MS (PwMS) who underwent clinical examination (Expanded Disability Status Scale – EDSS; Timed 25-Foot Walk Test - T25FW; and the Nine Hole Peg Test - 9HPT), general neuropsychological assessment (Brief Repeatable Battery of Neuropsychological Tests – BRBN, including the Symbol Digit Modalities Test - SDMT), social cognition evaluation (Reading the Mind in the Eyes Test), cognitive reserve questionnaire, and MRI (FreeSurfer). We also enrolled healthy subjects for comparison as a control group. Daily occupations (employment, money management, and driving abilities) were assessed in all individuals with questionnaires. ResultsWe included 62 PwMS (32 RRMS and 30 SPMS; mean age 42.8 years; median educational time 12.75 years) and 67 controls (mean age 39.7; median educational time 12.0 years) which were similar regarding demographics, education, and socioeconomic status (p > 0.1). Most PwMS (67.7%) had work-restrictions. They also reported fewer money management and driving abilities than controls (p < 0.001). Work-restriction was associated with physical disability (p = 0.006), SDMT and BRBN performance (p = 0.035 and p = 0.031, respectively), and T2-lesion volume (p = 0.022), with large effect sizes (d > 0.75). After hierarchical linear regression, money management was associated with hand dexterity, general and social cognition, and cognitive reserve (p < 0.03). Variables associated with driving abilities included fatigue, verbal fluency, striatum volume, and brain reserve (p < 0.05). ConclusionsPwMS have more frequent work-restrictions and impairment in money management and driving abilities compared to controls. Cognitive function, physical disability, and MS-lesion burden are strongly associated with work-restriction. Social cognition can also influence financial capacity. Cognitive and brain reserve can help retain some of these daily occupations.

46 Depression and Reward Responsiveness in Multiple Sclerosis

Objective:Depression is common in persons with MS (PwMS), substantially contributing to morbidity and mortality. Depression can dually impact PwMS as both a psychosocial reaction to living with the disease and a neurological effect of it. Cardinal features of depression include reduced ability to seek and experience pleasure, often attributed to dysregulation of the brain's reward system. People with depression exhibit atypical reward processing, as do fatigued PwMS. However, it is unclear whether MS itself affects reward processing, and whether it interacts with depression. The current study explored the associations of depression, MS, and their interaction on reward responsiveness. We hypothesized that depression and MS would independently be associated with poorer reward responsiveness and that they would interact synergistically to impair reward responsiveness.Participants and Methods:Forty PwMS and 40 healthy age- and education-matched healthy controls (HC) participated in a computerized switching task with high- and low-reward manipulations. The Chicago Multiscale Depression Inventory (CMDI) Mood subscale measured depressive symptoms. The Behavioral Inhibition/Activation Scales (BIS/BAS) measured self-reported reward responsiveness and behavioral inhibition. Switching task performance was measured as response time (RT) and accuracy. Performance differences between the high- and low-reward conditions represented performance-based reward responsiveness. Linear mixed effects models were used to estimate the associations of MS and depression with reward responsiveness, behavioral inhibition, and task performance.Results:Depression, but not MS, was associated with higher BIS scores (p=.007). Neither depression nor MS was associated with BAS subscales. On the switching task, participants who reported lower depression responded to reward such that they were slightly faster in the high-reward condition compared to the low-reward condition (p=.07). By contrast, in participants who reported higher depression, there was no effect of reward on response time. Additionally, MS (p=.009) and depression (p=.018) were each associated with slower response times. Regarding accuracy, no effects of reward were observed; however, there was an interaction between MS and depression. Among HC participants, depression was not related to accuracy. In comparison, PwMS who reported higher depression were more accurate than PwMS who reported less depression (p=.043).Conclusions:Consistent with hypotheses, higher depressive symptoms were associated with increased behavioral inhibition. Depression was not associated with self-reported reward responsiveness, but it was associated with reduced reward responsiveness on a cognitive task. Contrary to hypotheses, MS was not associated with reduced reward responsiveness. Additionally, higher depression and an MS diagnosis were related to slower response time, consistent with prior findings that psychomotor slowing is a hallmark feature of both disorders. Interestingly, we observed a unique behavioral trend in PwMS, such that PwMS with higher depressive symptoms were more accurate than PwMS with lower depressive symptoms, whereas this relationship was not present among HCs. Altogether, depression in both PwMS and cognitively healthy individuals may be associated with blunted reward responsiveness, but MS does not exacerbate this relationship. In fact, PwMS with depression may be more conscientious in their functioning and therefore perform better on cognitive task accuracy. Continued work should examine how reward processing and its underlying mechanisms may differ in depressed PwMS.

39 Co-Occurring Depression and Anxiety is Associated with Greater Cognitive Variability in Persons with Multiple Sclerosis

Objective:Research examining co-occurring anxiety and depression in persons with multiple sclerosis (PwMS) is scarce, though an estimated 20% of PwMS experience clinically significant anxiety and depression (Gascoyne et al., 2019). Recent work by Hanna &amp; Strober (2020) found that PwMS with comorbid anxiety and depression reported worse outcomes in all constructs of symptomatology, disease management, psychological well-being, and quality of life. However, it is unclear how co-occurring anxiety and depression symptoms may influence or exacerbate cognitive difficulties in PwMS. Further, considering there are high levels of comorbidity between depression, anxiety, and fatigue in PwMS, this study aims to examine the unique variances of depression, anxiety, co-occurring depression and anxiety, and fatigue on cognitive functioning.Participants and Methods:86 PwMS (F=65,M=21) completed a comprehensive neuropsychological battery that included self-report measures of anxiety, depression, and fatigue. An intraindividual variability (IIV) composite score was calculated by combining standardized intraindividual standard deviation and maximum discrepancy scores on measures of attention/processing speed and memory for each participant. Lower scores indicate worse performance (i.e., greater variability). A hierarchical regression was conducted with IIV as the outcome variable and with depression, anxiety, cognitive fatigue, physical fatigue, and the interaction between depression and anxiety as predictors. Expanded Disability Status Scale (EDSS) scores were included as a covariate.Results:The only model that included a statistically significant predictor of IIV was the final model, which included EDSS, depression, anxiety, cognitive fatigue, physical fatigue, and the interaction between depression and anxiety, F(6,77)=2.97, p=.01, AR2=.08. While the main effects of depression and anxiety were not significant, the interaction between depression and anxiety was significant, F(6,77)=7.20, p=.01, n2=.09. Simple effects tests revealed that the relationship between IIV and anxiety was marginally significant for those at the cutoff for clinical depression (square root BDI-FS=2; BDI-FS=4), F(6,77)=3.52, p=.07, n2=.04. However, the effect of anxiety on IIV increased as depression increased. For example, in those with high levels of depression (1.5 SD above the mean), there was a significant relationship between anxiety and IIV, F(6,77)=4.16, p=.04, n2=.05, though this was not the case for those with low levels of depression (1.5 SD below the mean), F(6,77)=0.01, p=.92, n2=.00.Conclusions:The interaction between depression and anxiety predicted variability in performance such that those with high levels of depression and anxiety demonstrated significantly greater IIV. Since dispersion is considered a marker for neurocognitive integrity, this may suggest that co-occurring psychological disturbances are associated with poorer cognitive integrity, an important consideration for interventions and outcomes. While interventions aimed at treating co-occurring depression and anxiety have been largely overlooked within the MS literature (Butler et al., 2016), transdiagnostic interventions have been beneficial for general adult populations with co-occurring anxiety and depression (McEvoy et al., 2009). Future work should examine the efficacy of interventions aimed at addressing co-occurring depression and anxiety in PwMS, as this may help to improve cognitive functioning, as well as perception of functioning, which will likely further improve quality of life and overall well-being.