Cognitive rehabilitation effects on grey matter volume and Go-NoGo activity in progressive multiple sclerosis: results from the CogEx trial.

BACKGROUND: Research on cognitive rehabilitation (CR) and aerobic exercise (EX) to improve cognition in progressive multiple sclerosis (PMS) remains limited. CogEx trial investigated the effectiveness of CR and EX in PMS: here, we present MRI substudy volumetric and task-related functional MRI (fMRI) findings. METHODS: Participants were randomised to: 'CR plus EX', 'CR plus sham EX (EX-S)', 'EX plus sham CR (CR-S)' and 'CR-S plus EX-S' and attended 12-week intervention. All subjects performed physical/cognitive assessments at baseline, week 12 and 6 months post intervention (month 9). All MRI substudy participants underwent volumetric MRI and fMRI (Go-NoGo task). RESULTS: 104 PMS enrolled at four sites participated in the CogEx MRI substudy; 84 (81%) had valid volumetric MRI and valid fMRI. Week 12/month 9 cognitive performances did not differ among interventions; however, 25-62% of the patients showed Symbol Digit Modalities Test improvements. Normalised cortical grey matter volume (NcGMV) changes at week 12 versus baseline were heterogeneous among interventions (p=0.05); this was mainly driven by increased NcGMV in 'CR plus EX-S' (p=0.02). Groups performing CR (ie, 'CR plus EX' and 'CR plus EX-S') exhibited increased NcGMV over time, especially in the frontal (p=0.01), parietal (p=0.04) and temporal (p=0.04) lobes, while those performing CR-S exhibited NcGMV decrease (p=0.008). In CR groups, increased NcGMV (r=0.36, p=0.01) at week 12 versus baseline correlated with increased California Verbal Learning Test (CVLT)-II scores. 'CR plus EX-S' patients exhibited Go-NoGo activity increase (p<0.05, corrected) at week 12 versus baseline in bilateral insula. CONCLUSIONS: In PMS, CR modulated grey matter (GM) volume and insular activity. The association of GM and CVLT-II changes suggests GM plasticity contributes to cognitive improvements. TRIAL REGISTRATION NUMBER: NCT03679468.

Drop-out, adherence, and compliance in randomized controlled trials of exercise training in multiple sclerosis: Short report.

We documented reporting and rates of drop-out, adherence, and compliance from 40 randomized controlled trials (RCTs) included in our meta-analysis on safety of exercise training (ET) in MS. We adopted definitions and metrics of adherence and compliance provided by the MoXFo adherence group. Drop-out was reported in 100% of the RCTs and approximated 10% for intervention and control conditions. Adherence and compliance were reported in approximately 50% and 10% of the RCTs, respectively, and approximated 80% and 70%, respectively. Standardized metrics for reporting adherence and compliance are important in future RCTs for understanding the impact on outcomes and translation of research evidence into practice.

Study protocol: exercise training for treating major depressive disorder in multiple sclerosis.

BACKGROUND: Major depressive disorder (MDD) is prevalent, yet sub-optimally treated among persons with multiple sclerosis (MS). We propose that exercise training may be a promising approach for treating depression in persons with MS who have MDD. Our primary hypothesis predicts a reduction in depression severity immediately after an exercise training intervention compared with minimal change in an attention control condition, and the reduction will be maintained during a follow-up period. METHODS: This study involves a parallel-group, assessor-blinded RCT that examines the effect of a 4-month home-based exercise training intervention on depression severity in a sample of persons with MS who have MDD based on the MINI International Neuropsychiatric Interview. The primary outcomes of depression severity are the Patient Health Questionnaire-9 and Hamilton Depression Rating Scale. Participants (N = 146) will be recruited from within 200 miles of the University of Illinois at Chicago and randomized (1:1) into either a home-based exercise training condition or control condition with concealed allocation. The exercise training and social-contact, attention control (i.e., stretching) conditions will be delivered remotely over a 4-month period and supported through eight, 1:1 Zoom-based behavioral coaching sessions guided by social-cognitive theory and conducted by persons who are uninvolved in screening, recruitment, random assignment, and outcome assessment. We will collect outcome data at 0, 4 and 8 months using treatment-blinded assessors, and data analyses will involve intent-to-treat principles. DISCUSSION: If successful, the proposed study will provide the first Class I evidence supporting a home-based exercise training program for treating MDD in persons with MS. This is critical as exercise training would likely have positive secondary effects on symptoms, cognition, and quality of life, and provide a powerful, behavioral approach for managing the many negative outcomes of MDD in MS. The program in the proposed research is accessible and scalable for broad treatment of depression in MS, and provides the potential for integration in the clinical management of MS. TRIAL REGISTRATION: The trial was registered on September 10, 2021 at clinicaltrials.gov with the identifier NCT05051618. The registration occurred before we initiated recruitment on June 2, 2023.

Inverse association between arterial stiffness and perceived fatigue independent of disability status and BMI in multiple sclerosis.

INTRODUCTION: Multiple sclerosis (MS) is an immune-mediated, neurodegenerative disease of the central nervous system. Fatigue represents one of the most prevalent and limiting symptoms of MS, and is associated with vascular dysfunction, notably increased arterial stiffness. OBJECTIVE: This study examined the relationship between arterial stiffness and perceived fatigue in persons with MS. METHODS: The sample of 52 persons with MS (71.2% Female; Age: 46.7 ± 12.3 yrs.) completed arterial stiffness and fatigue assessments as baseline for an exercise training intervention. Applanation tonometry measured arterial stiffness, pulsatility and waveform characteristics, and yielded the following outcomes: carotid-femoral pulse wave velocity (cfPWV), carotid pulse-pressure (cPP), and aortic augmentation pressure (AP). Perceived fatigue was measured using the Fatigue Severity Scale (FSS). RESULTS: The mean (SD) scores for cfPWV, cPP, and AP were 7.0 ± 1.8 m/s, 35.7 ± 8.8 mmHg, 8.2 ± 6.2 mmHg, respectively. The mean (SD) FSS score was 4.6 ± 1.4 and indicated elevated fatigue. There were statistically significant (p < .05) inverse correlations between cfPWV (r = -.32), cPP (r = -.37) and AP (r = -.32) with FSS scores, and the correlations remained significant even after controlling for disability, body mass index, age, and sex. CONCLUSION: Our results indicate a consistent pattern of inverse relationships between arterial stiffness, pulsatility, and waveforms with fatigue independent of disability, body mass index, age, and sex in MS. This could be explained by lower sympathetic activation linking higher arterial stiffness, pulsatility and augmentation pressure with lower fatigue in persons with MS.

Comorbid Conditions and Physical Function in Adults With Multiple Sclerosis.

OBJECTIVE: We examined the total number of comorbid conditions as a correlate of physical function in persons with multiple sclerosis (MS). We further identified the presence of common comorbid conditions and examined physical function outcomes based on presence or absence of the comorbid conditions in persons with MS. DESIGN: Cross-sectional, comparative study. SETTING: University-based laboratory. PARTICIPANTS: Two hundred seven persons with MS (N=207) completed the study. MAIN OUTCOME MEASURES: Participants provided demographic, clinical, and comorbidity information. Participants then completed the 6-minute walk (6MW), timed 25-foot walk (T25FW), timed Up and Go (TUG), and short physical performance battery (SPPB). INTERVENTIONS: Not applicable. RESULTS: The number of comorbid conditions was associated with 6MW, T25FW, TUG, and SPPB scores (all P≤.001). Persons with MS who had hypertension performed worse on the 6MW, T25FW, TUG, and SPPB than persons without hypertension. Persons who had osteoarthritis performed worse on the 6MW, T25FW, and SPPB than persons without osteoarthritis. CONCLUSIONS: The results demonstrate that persons who report more comorbid conditions have worse physical function, and this may largely be associated with hypertension or osteoarthritis. There are opportunities for the design of behavioral interventions that target physical activity and/or diet for improving physical function via comorbid conditions in persons with MS.

Social Cognitive Theory Variables as Correlates of Physical Activity Behavior Among Hispanics With Multiple Sclerosis.

OBJECTIVE: To examine the association between social cognitive theory (SCT) variables and physical activity (PA) behavior in Hispanic adults with multiple sclerosis (MS). DESIGN: Observational, survey study. SETTING: General community. PARTICIPANTS: Inclusion criteria: (a) age 18 years or older, (b) self-identify as Hispanic or Latino, (c) diagnosis of MS, and (d) English or Spanish as primary language. Two hundred forty-three individuals opened the survey, 24 individuals did not meet inclusion criteria, and 66 individuals were excluded due to not completing any of the SCT variable measures (N=153). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE(S): PA was measured using the Godin Leisure Time Exercise Questionnaire (GLTEQ) total and Health Contribution Scores (HCS). SCT variables included standard measures of exercise self-efficacy, planning, goal setting, outcome expectations, social support, and functional impairment. RESULTS: The final sample included 153 participants with a mean (SD) age of 43 (11) years, 78% identified as women, 57% were employed, and 63% had a college degree or higher. The mean (SD) MS disease duration was 11 (9) years, 74% of participants reported relapsing remitting MS, and median (interquartile range) Patient Determined Disease Steps (PDDS) score was 3.0 (3.0). Significant correlations were observed between all SCT variables and both GLTEQ total and GLTEQ HCS scores (P<.001). Forward stepwise regression with Akaike's Information Criterion (AICC) identified PDDS, age, exercise planning, exercise self-efficacy, and exercise goal setting as the most appropriate covariates and SCT variables to include in a multivariable model examining independent contributions on GLTEQ HCS scores. The multivariable, linear regression analysis indicated that PDDS (Standardized B=-.280, P<.001), exercise planning (Standardized B=.214, P<.05), and exercise self-efficacy (Standardized B=.183, P<.05) explained 42.4% of variance in GLTEQ HCS scores. CONCLUSIONS: This study provides a contribution to the literature by identifying SCT variables that correlate with PA behavior among Hispanics with MS that may guide the creation of culturally appropriate PA programs.

Variables Associated With Moderate to High Loneliness Among Individuals Living With Spinal Cord Injuries and Disorders.

OBJECTIVE: To identify variables independently associated with moderate to high loneliness in individuals living with Spinal Cord Injuries or Disorders (SCI/D). DESIGN: A cross-sectional, national survey of a random sample of community-dwelling Veterans with SCI/D in the United States. Survey methodology was used to collect data on demographic and injury characteristics, general health, chronic and SCI-secondary conditions, and loneliness. SETTING: The VHA SCI/D System of Care including 25 regional SCI/D Centers (or Hubs). PARTICIPANTS: Among 2466 Veterans with SCI/D, 592 completed surveys (24%). Most participants were men (91%), white (81%), not currently married (42%), had tetraplegia (33%), and on average injured for 18 years at the time of data collection (N=562). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: The dependent variable, loneliness, was collected using the UCLA-3 instrument. Loneliness was dichotomized into never/low loneliness and moderate/high loneliness (UCLA score ≥ 4). RESULTS: Bivariate analyses assessed unadjusted associations in demographics, injury characteristics, chronic disease, and SCI-secondary conditions. Multivariable logistic regression was used to identify factors independently associated with moderate/high loneliness. Participants had a mean loneliness score of 5.04, SD=1.99. The point prevalence of moderate to high loneliness was 66%. Lower duration of injury, paraplegia, being unmarried, being in fair/poor general health, having dysfunctional sleep, and having a diagnosis of bowel dysfunction were each independently associated with greater odds of moderate/high loneliness. CONCLUSIONS: Findings suggest that interventions to reduce/manage loneliness in the Veteran SCI/D population should focus on those who are more newly injured, have paraplegia, currently unmarried, have bowel problems, and experience dysfunctional sleep.

Physical activity and arterial stiffness: is body fat a mediator?

PURPOSE: Physical activity (PA) and body fat percentage (%BF) are independently associated with arterial stiffness, but it has not been explored if there is an associative pathway among these variables. This study examined whether %BF mediates the relationship between PA or sedentary behavior levels with arterial stiffness. METHODS: Fifty adults (1:1 men:women; age 28 ± 11 year) had carotid-femoral pulse wave velocity (CF-PWV) measured by applanation tonometry, %BF by bioelectrical impedance, and PA levels by accelerometry. Accelerometer data determined minutes per day spent in sedentary, light, moderate-to-vigorous physical activity (MVPA), and Total PA. RESULTS: Pearson correlation indicated statistically significant associations among age, %BF, CF-PWV, MVPA, and Total PA (r = 0.34-0.65, p < 0.05). Sedentary and light PA were not associated with CF-PWV. Mediation analysis indicated significant total effects of MVPA (ß = - 0.34, p = 0.044) and age (ß = 0.65, p < 0.001) on CF-PWV. %BF mediated the relationship between Total PA and CF-PWV due to indirect effect of Total PA on %BF (ß = - 0.34, p = 0.02) and %BF on CF-PWV (ß = 0.44, p = 0.002), and partially mediated the relationship between age and CF-PWV (ß = 0.54, p < 0.001). Total PA retained its significant effect on %BF (ß = - 0.28, p = 0.04) and the effect of %BF on CF-PWV remained significant (ß = 0.26, p = 0.03), despite age having a significant effect on both %BF (ß = 0.31, p = 0.023) and CF-PWV (ß = 0.54, p < 0.001). CONCLUSIONS: %BF mediated the relationship between Total PA and arterial stiffness, even after accounting for age. Engagement in more Total PA may help to reduce %BF, resulting in decreased arterial stiffness.

Randomized Controlled Trial of the Behavioral Intervention for Physical Activity in Multiple Sclerosis Project: Response Heterogeneity and Predictors of Change.

BACKGROUND: We reported that a social cognitive theory-based (SCT), Internet-delivered behavioral intervention increased device-measured minutes/day of moderate-to-vigorous physical activity (MVPA) over a 6-month period among persons with multiple sclerosis (MS). This paper examined the pattern and predictors of heterogeneity in change for MVPA. Based on previous research, we hypothesized that mild MS disability, fewer MS symptoms, lower baseline MVPA, and positive SCT characteristics (e.g., high exercise self-efficacy) would be associated with greater change in MVPA. METHOD: Persons with MS (N = 318) were randomized into behavioral intervention (n = 159) or attention/social contact control (n = 159) conditions that were administered via Internet websites and supported with behavioral coaching. Demographic, clinical, symptom, behavioral, and SCT data were from before the 6-month period of delivering the conditions, and MVPA data were from before and after the 6-month period. We examined heterogeneity based on waterfall plots, box plots, and the Levene statistic. We identified predictors of MVPA change using bivariate correlation and multiple, linear regression analyses per condition. RESULTS: The Levene statistic indicated statistically significant heterogeneity of variances for MVPA change between conditions (p = .003), and the waterfall plots and box plots indicated greater heterogeneity in MVPA change for the behavioral intervention. MVPA change score was correlated with baseline MVPA (r = - .33 and r = - .34, p = .0004 and p = .0001) in both conditions and walking impairment (r = - .188, p = .047) and race (r = .233, p = .014) in the behavioral intervention condition. The regression analysis indicated that baseline MVPA (Standardized B = - .449, p = .000002), self-reported walking impairment (Standardized B = - .310, p = .0008), and race (Standardized B = .215, p = .012) explained 25.6% of variance in MVPA change for the behavioral intervention condition. CONCLUSION: We provide evidence for walking impairment, baseline MVPA, and race as predictors of the heterogeneity in the pattern of MVPA change with a behavioral intervention.

Cross-sectional, comparative study of health-related quality of life across the adult lifespan in multiple sclerosis.

PURPOSE: This study examines the independent and interactive effects of age and multiple sclerosis (MS) on health-related quality of life (HRQOL). MATERIALS AND METHODS: The sample included persons with MS (n = 207) and healthy controls (HCs; n = 99) divided into three age groups (young, middle-aged, and older adults) who completed a battery of questionnaires, including the 36-item Short-Form Health Survey (SF-36) as a measure of HRQOL. The SF-36 yielded scores for the Physical Component Summary (PCS) (i.e. physical HRQOL) and Mental Component Summary (MCS) (i.e. mental HRQOL). The data were analyzed using two-way MANOVA. RESULTS: There was no interaction between age and disease status on HRQOL, but there were significant main effects of age and disease status on HRQOL. HRQOL was significantly lower in participants with MS than HCs, regardless of age. Physical HRQOL was lower, whereas mental HRQOL was higher across age groups. CONCLUSION: The findings suggest that future research should develop behavioral and rehabilitation approaches that are applicable for improving HRQOL across the lifespan in persons with MS, particularly for physical HRQOL in older adults with MS.

Preferred Behavior Change Techniques for Physical Activity Interventions among Persons Newly Diagnosed with Multiple Sclerosis: A Qualitative Study.

There is increasing interest by researchers and clinicians in behavior change interventions for promoting physical activity in persons newly diagnosed with MS. Ideally, such interventions require the delivery of behavior change techniques (BCTs) based on theory and the selection of BCTs might further require tailoring for this MS subpopulation. The current study examined BCTs preferred by persons newly diagnosed with MS for informing the design and delivery of physical activity behavior change interventions in early-stages of MS. We recruited and interviewed 20 persons newly diagnosed with MS (i.e., disease duration ≤ 2 years). The interviews were conducted online via video conferencing platform and followed a semi-structured script. During the interviews, participants provided opinions regarding an ideal physical activity behavior change program, and the opinions of participants were mapped with the Intervention Functions of the Behavior Change Wheel, BCTs, and BCT groups. Ten frequently mentioned BCTs were identified as preferred strategies for a physical activity behavior change intervention among persons newly diagnosed with MS. These BCTs focused on providing social support, skills and strategies for physical activity performance and regulation, and knowledge on benefits of physical activity in MS. This research provides a refined list of BCTs that can be included when designing tailored physical activity behavior change interventions for persons newly diagnosed with MS.

Oxygen cost of walking and its relationship with body composition in multiple sclerosis.

BACKGROUND/OBJECTIVES: This cross-sectional study examined the relationship between the oxygen (O2) cost of walking and body composition metrics, while considering potential covariates such as disability status, step length, and cadence, in persons with multiple sclerosis (MS). SUBJECTS/METHODS: The sample included 63 persons with MS across a wide distribution of body mass index (BMI). O2 cost of walking was assessed using portable, indirect calorimetry, and percent body fat (%Fat), fat-free mass (FFM), bone mineral content, bone mineral density (BMD), and weight/FFM were determined from dual-energy x-ray absorptiometry. Other outcome measures included step length, cadence, physical activity, and disability status. RESULTS: The O2 cost of walking had small-to-moderate associations with BMI (rs = -31, p = 0.015), %Fat (rs = -0.26, p = 0.041), and BMD (rs = -0.31, p = 0.013). O2 cost of walking was significantly associated with these outcomes even after controlling for age, sex, disability status, and gait outcomes. The O2 cost of walking was further significantly associated with shorter step length (rs = -0.40, p = 0.001), slower cadence (rs = -0.38, p = 0.002), and higher disability status (rs = 0.44, p < 0.001), but not physical activity. Body composition metrics were not associated with gait parameters, physical activity or disability status in our sample of persons with mild-to-moderate MS. CONCLUSIONS: The results indicated that higher O2 cost of walking was associated with lower fat and worse bone health after taking factors such as disability status into consideration. Researchers may focus on interventions that change body composition, or perhaps gait profiles, as possible approaches for changing O2 cost of walking and its consequences such as disability status in persons with MS.

Randomized, Placebo-Controlled, Single-Blind Study of Lutein Supplementation on Carotenoid Status and Cognition in Persons with Multiple Sclerosis.

BACKGROUND: Multiple sclerosis (MS) is traditionally managed using disease-modifying pharmaceutical therapies as a first line approach for treatment, yet there is increasing interest in lifestyle factors, particularly diet, for managing disease outcomes. Lutein has neuroprotective properties in healthy adults, but no previous research has examined the effects of lutein supplementation in persons with MS. OBJECTIVES: This study aimed to investigate the efficacy of 4-mo lutein supplementation on carotenoid status and cognition in persons with relapse-remitting MS (RRMS). METHODS: A randomized controlled, single-blind research design was used among adults with RRMS (N = 21). Participants were randomized into placebo (n = 9) or treatment (20-mg/d lutein, n = 12) groups with outcomes measured before and after 4 mo. Macular pigment optical density (MPOD) was assessed using heterochromatic flicker photometry. Skin carotenoids were assessed using reflection spectroscopy. Serum lutein was measured using high-performance liquid chromatography. Cognition was assessed via the Eriksen flanker with event-related potentials, spatial reconstruction, and the symbol digit modalities tests. RESULTS: There was a significant group by time interaction for MPOD (F = 6.74, P = 0.02), skin carotenoids (F = 17.30, P < 0.01), and serum lutein (F = 24.10, P < 0.01), whereby the treatment group improved in all carotenoid outcomes. There were no significant group by time interactions for cognitive and neuroelectric outcomes. However, increase in MPOD was positively associated with accuracy during the flanker incongruent trials (r = 0.55, P = 0.03) and the spatial memory task (r = 0.58, P = 0.02) among treatment participants. CONCLUSIONS: Lutein supplementation increases carotenoid status among persons with RRMS. There is no significant effect on cognitive function but change in macular carotenoids is selectively associated with improved attention and memory. This study provides preliminary support for a fully powered study targeting retinal and neural carotenoids for cognitive benefits in persons with MS. This trial was registered at clinicaltrials.gov as NCT04843813.

Arterial stiffness in persons with multiple sclerosis and controls: Does aerobic fitness account for group differences?

Vascular function is worse in multiple sclerosis (MS) than healthy controls perhaps based on differences in aerobic fitness. We compared carotid-femoral pulse wave velocity (cfPWV) and augmentation index (AIx75) between MS and controls while accounting for aerobic fitness. Aerobic fitness was measured as peak oxygen consumption on a recumbent stepper. cfPWV and AIx75 were measured using applanation tonometry. Persons with MS demonstrated lower aerobic fitness and higher cfPWV, but no difference in AIx75 compared with controls. The difference in cfPWV remained statistically significant after controlling for aerobic fitness, suggesting that arterial stiffness might reflect underlying pathophysiology processes of MS.

Primary results of a phase-III, randomized controlled trial of the Behavioral Intervention for increasing Physical Activity in Multiple Sclerosis project.

BACKGROUND: We undertook a phase-III, randomized controlled trial (RCT) that examined the effectiveness of a behavioral intervention based on social cognitive theory (SCT) and delivered through the Internet using e-learning approaches for immediate and sustained increases in physical activity among persons with multiple sclerosis (MS). METHOD: The study followed a parallel group RCT design. Persons with MS (N = 318) were randomized into either behavioral intervention (n = 159) or attention/social contact control (n = 159) conditions. The conditions were administered over a 6-month period by persons who were uninvolved in screening, recruitment, random assignment, and outcome assessment. There was a 6-month follow-up period without access of conditions. We collected outcome data every 6 months over the 12-month period. The primary outcome was device-measured minutes/day of moderate-to-vigorous physical activity (MVPA). The data analysis involved a modified intent-to-treat approach (i.e. those who received the allocated conditions) using a linear mixed model. RESULTS: There was a significant group by time interaction on the primary outcome of device-measured minutes/day of MVPA (p < 0.005). MVPA was increased immediately after the 6-month period in the behavioral intervention compared with control, and this difference was sustained over the 6-month follow-up. CONCLUSION: This study provides evidence for the effectiveness of a widely scalable approach for increasing MVPA in persons with MS.

The MoXFo initiative - adherence: Exercise adherence, compliance and sustainability among people with multiple sclerosis: An overview and roadmap for research.

We know very little about exercise adherence, compliance and sustainability in multiple sclerosis (MS), yet adherence is seemingly important for yielding immediate and sustained health benefits. This paper is focused on exercise adherence, compliance and sustainability in the context of informing research and practice involving MS. This focus is critical for clarifying terminology for future research and providing a roadmap guiding clinical research and practice. Our objective was accomplished through a narrative summary of the literature by a panel of experts on exercise adherence from the Moving Exercise Research in Multiple Sclerosis Forward (MoXFo) initiative and a concluding summary of the state of the literature and future research directions. The panel of experts identified three overall themes (Background and Importance; Understanding and Promoting Exercise Adherence, Compliance and Sustainability and Challenges to Exercise Adherence, Compliance and Sustainability) that represented a categorization of nine subthemes. These overall themes and subthemes formed the basis of our recommendations regarding future research broadly involving exercise adherence in MS. Overall, there is limited evidence on rates and determinants of exercise adherence and compliance in MS, and little is known about techniques and interventions for immediate and long-term exercise behaviour change.

Safety of exercise training in multiple sclerosis: An updated systematic review and meta-analysis.

BACKGROUND: A review of the safety profile of exercise training in multiple sclerosis (MS) has not been conducted since 2013. OBJECTIVE: We undertook a systematic review and meta-analysis of randomised controlled trials (RCTs) of exercise training published since 2013 and quantified estimated population risks of clinical relapse, adverse events (AE) and serious adverse event (SAE). METHODS: Articles reporting safety outcomes from comparisons of exercise training with non-exercise among persons with MS were identified. The risk of bias was established from study's internal validity assessed using Physiotherapy Evidence Database (PEDro). Rates and estimated mean population relative risks (RRs; 95% confidence interval (CI)) of safety outcomes were calculated, and random-effects meta-analysis estimated the mean RR. RESULTS: Forty-six interventions from 40 RCTs (N = 1780) yielded 46, 40 and 39 effects for relapse, AE, adverse effects and SAE, respectively. The mean population RRs ((95% CI), p-value) for relapse, AE and SAE were 0.95 ((0.61, 1.48), p = 0.82), 1.40 ((0.90, 2.19), p = 0.14) and 1.05 ((0.62, 1.80), p = 0.85), respectively. No significant heterogeneity is observed for any outcome. CONCLUSION: In studies that reported safety outcomes, there was no higher risk of relapse, AE, adverse effects or SAE for exercise training than the comparator. Exercise training may be promoted as safe and beneficial to persons with MS.

Blood pressure and cognition in older adults with multiple sclerosis: preliminary examination.

BACKGROUND: Comorbid conditions, particularly vascular comorbidity, are common in MS and may hasten the CNS damage and disease manifestations. We undertook a preliminary examination of the association between blood pressure (BP) and cognitive function in samples of older adults with MS and healthy controls. METHODS: Older adults with MS (n = 29) and healthy controls (n = 29) completed the Brief International Cognitive Assessment for MS (BICAMS) battery and underwent assessment of BP. The data were analyzed using the Baron and Kenny approach for examining blood pressure as an explanatory variable for group differences in cognition. RESULTS: The MS group, as expected, had significantly lower California Verbal Learning Test-II (CVLT-II) z-scores from the BICAMS and higher diastolic BP (DBP) than healthy controls. DBP had statistically significant correlations with CVLT-II z-scores in the overall sample (r = - .42) and MS subsample (r = - .51), but not healthy controls(r = - .29); the correlation was not attenuated when controlling for age and disability status in the MS subsample (pr = - .48). Group initially explained 6% of the variance in z-scores from the CVLT-II (ß = - 0.24). The inclusion of DBP accounted for an additional 14% of the variance in z-scores from the CVLT-II, and DBP(ß = - 0.39), but not group (ß = - 0.13), was a significant correlate of CVLT-II z-scores; the results were unchanged when controlling for anxiety and depression scores. CONCLUSION: Our results provide preliminary, cross-sectional support for future population-based research examining DBP, hypertension, and verbal memory in older adults with MS.

Diet, Physical Activity, and Stress Among Wheelchair Users With Multiple Sclerosis: Examining Individual and Co-Occurring Behavioral Risk Factors.

OBJECTIVE: This study examined individual and co-occurring behavioral risk factors (diet, exercise, and stress) in wheelchair users with multiple sclerosis (MS) and potential association with MS symptoms (ie, fatigue, depression, anxiety, pain, sleep, and health-related quality of life [HRQOL]). DESIGN: Survey. SETTING: General Community. PARTICIPANTS: One hundred twenty-three wheelchair users with MS completed this study (N=123). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Participants were mailed instructions for accessing online questionnaires (demographic and clinical characteristics, Godin Leisure-Time Exercise Questionnaire, Perceived Stress Scale, Automated Self-Administered 24-Hour Dietary Assessment Tool, and MS symptoms). RESULTS: Standard cut-points were used to categorize behavioral risk factors and then identify the extent and distribution of these behaviors both individually and co-occurring. We then analyzed the associations between behavioral risk factors and MS symptoms using bivariate correlation analyses and Mann-Whitney U tests. The mean age of participants was 60.6±10.0 years, 76% identified as women, 82% had a progressive disease course, and the mean MS duration was 23.0±9.7 years. Seven participants were classified as having 0 negative health behaviors, 41 participants had 1 negative health behavior, 49 participants had 2 negative health behaviors, and 26 participants had 3 negative health behaviors. The number of negative health behaviors was significantly correlated with HRQOL (physical, r=.30; psychological, r=.47), sleep (r=.25), depressive symptoms (r=.36), and anxiety (r=.43). Mann-Whitney U tests indicated greater fatigue, depression, and anxiety as well as lower sleep quality and HRQOL among participants who reported 2 or 3 behavioral risk factors compared with 0 or 1 behavioral risk factor. CONCLUSIONS: Future research should examine the design and implementation of multiple health behavior change interventions targeting co-occurring behavioral risk factors among wheelchair users with MS.

Physical Activity and Quality of Life in Persons Newly Diagnosed With Multiple Sclerosis: A Cross-sectional Study.

OBJECTIVE: To examine the association between physical activity (PA) and quality of life (QOL) in persons newly diagnosed with multiple sclerosis (MS) who have been under-represented in MS research. DESIGN: Cross-sectional study with secondary data analysis. SETTING: General community. PARTICIPANTS: The study included 152 persons newly diagnosed with MS (ie, diagnosed with MS within the past 2 years) aged 18 and older (N=152). MAIN OUTCOME MEASURES: Participants completed the Godin Leisure-Time Exercise Questionnaire to measure PA. QOL, disability status, fatigue, mood, and comorbidity were assessed using the 12-Item Short Form Survey (SF-12), Patient Determined Disease Steps, Hamburg Quality of Life Questionnaire Multiple Sclerosis, and comorbidity questionnaire. RESULTS: The bivariate correlations indicated that PA was significantly and positively associated with the physical component of QOL (ie, SF-12 PCS) (r=0.46). The stepwise multiple linear regression analysis indicated PA as associated with SF-12 PCS (ß=0.43, R2=0.17) when solely included in the model. After controlling for fatigue, mood, disability status, and comorbidity as covariates (R2=0.63), the association between PA and SF-12 PCS was still statistically significant, but attenuated in magnitude (ß=0.11). CONCLUSIONS: This study observed that PA was significantly associated with the physical component of QOL in persons newly diagnosed with MS, even after controlling for covariates. The findings underscore the importance of developing behavior change interventions targeting PA while addressing the roles of fatigue and disability status for enhancing the physical component of QOL of this MS subpopulation.