Fitness and cognitive processing speed in persons with multiple sclerosis

Background: Cognitive impairment is prevalent, disabling, and poorly managed in persons with MS. To date, two studies have identified aerobic capacity as a correlate of cognition in MS, but there has yet to be an investigation of multiple domains of fitness as correlates of cognition in this population. Such an examination is important for identifying the appropriate modes of exercise training for possibly improving cognition. Objective: This study examined the relationships among aerobic capacity, muscle strength, and balance with cognitive function in persons with MS. Methods: 31 persons with MS and 31 controls matched by age, height, weight, and sex completed two neuropsychological measures of cognitive processing speed (PASAT and SDMT). Participants underwent an incremental exercise test to exhaustion on a cycle ergometer as a measure of aerobic capacity; three maximal isometric extensions and one maximal isometric flexion with each knee on an isokinetic dynamometer at three different joint angles as a measure of muscular strength; and stood on a force platform without shoes for 30 seconds with eyes open to measure postural sway. Results: Independent samples t-tests indicated that MS and control groups differed in PASAT score (t = −2.13, p = .04), SDMT score (t = −2.69, p = .01), aerobic capacity (t = −2.99, p < .01), and balance (t = 4.06, p < .01), but not in muscular strength. Cognitive processing speed was significantly associated with aerobic capacity (r = .43 and .44) and balance (r= −.52 and −.52), but not muscular strength in the overall and MS samples, respectively. Lastly, hierarchical regression analysis indicated that aerobic capacity (β = .27) and balance (β = −.40) accounted for differences in cognitive processing speed between MS and control groups. Conclusions: Aerobic capacity and balance, but not muscular strength, are associated with cognitive processing speed in persons with MS, suggesting that aerobic exercise and balance training are avenues for possibly improving cognitive impairment in this population

The acute effects of varying intensities of treadmill walking exercise on cognition in persons with multiple sclerosis

Background: Exercise training represents a promising approach for managing cognitive impairment in persons with multiple sclerosis (MS). There is preliminary evidence that treadmill walking exercise might be the modality of exercise that exerts the greatest beneficial effects on executive control in persons with mild MS disability. However, the dose-dependent effects of varying intensities of treadmill walking exercise on this cognitive function are unknown. Such an investigation is critical for providing the final data for delineating the optimal exercise stimulus (or stimuli) for improving executive control in persons with MS. Objectives: The present study compared the acute effects of light, moderate, and vigorous intensity treadmill walking exercise on multiple aspects of executive control (i.e., interference control and response inhibition) relative to quiet rest in 24 persons with mild MS disability, using a within-subjects, repeated-measures experimental design. Methods: Participants completed four experimental conditions that consisted of 20 minutes of light intensity treadmill walking exercise, moderate intensity treadmill walking exercise, vigorous intensity treadmill walking exercise, and quiet rest in a randomized, counterbalanced order. Participants underwent a modified-flanker task and Go/No-Go task as measures of executive control immediately prior to and following each condition. Results: Repeated-measures ANOVAs indicated large, statistically significant pre-to-post reductions in the cost of interfering stimuli on reaction time, but not accuracy, on the modified-flanker task for light, moderate, and vigorous intensity exercise compared with quiet rest (F(3,69)=4.27,p=.01,ηp2=.16) that were similar in magnitude. There further were no overall effects of exercise intensities on percent accuracy from the Go/No-Go task (F(3,69)=0.33,p=.81,ηp2=.01), compared with quiet rest. Conclusions: The present results support light, moderate, and vigorous intensity treadmill walking as exercise stimuli that might particularly benefit speed-related aspects of executive control (i.e., interference control of reaction time). This represents the final step in delineating the optimal exercise stimuli for inclusion in a subsequent longitudinal exercise training intervention for improving this cognitive function in persons with mild MS disability

Validation of the Godin Leisure-Time Exercise Questionnaire Classification Coding System Using Accelerometry in Multiple Sclerosis

Objective: There have been recent efforts toward creating a health contribution score (HCS) from the Godin Leisure-Time Exercise Questionnaire (GLTEQ) that reflects public-health guidelines for levels of moderate-to-vigorous physical activity (MVPA). The HCS yields categories of insufficiently active (less substantial or low benefits), moderately active (some benefits), and active (substantial benefits). The present study examined the validity of the GLTEQ HCS and its categories as reflecting levels of MVPA in multiple sclerosis (MS). Method: The sample included 684 persons with MS. Participants wore an accelerometer on an elastic belt around the waist above the nondominant hip during the waking hours of the day over a 7-day period and completed the GLTEQ. Results: The data analyses supported a large correlation between the GLTEQ HCS and accelerometer-measured MVPA, r = .46, p \u3c .0001, but small correlations with accelerometer-measured light physical activity (LPA), r = .16, p \u3c .001 and sedentary time, r = −.13, p = .001. There further was a large difference in accelerometer-measured MVPA between categories of physical activity levels (i.e., insufficiently active vs. active) based on the GLTEQ HCS (d = 0.89), but small differences in LPA (d = 0.39) and sedentary time (d = −0.31). Those results were unchanged in additional data analyses accounting for LPA and sedentary behavior. Conclusions: The GLTEQ HCS and categories primarily reflect MVPA rather than LPA and sedentary behavior in persons with MS

Physical Function Across the Lifespan in Adults with Multiple Sclerosis: An Application of the Short Physical Performance Battery

Background Multiple sclerosis (MS) typically has its onset in early and middle adulthood, but the population is steadily becoming more dominated by older adults. One of the primary consequences of both MS and aging involves declines of lower extremity physical function and mobility. This cross-sectional study compared physical function status based on Short Physical Performance Battery (SPPB) summary and component scores between persons with MS and healthy controls across 6 age groups. We further examined associations between SPPB summary scores and component scores as well as associations between summary scores and measures of physical and cognitive function for identifying the strongest correlates of SPPB summary scores. Methods The study involved secondary analysis of cross-sectional data from multiple studies. Ambulatory adults with MS who were relapse-free for the last 30 days were recruited, and controls were recruited based on similar criteria to adults with MS except without the diagnosis of MS or relapses. The sample of 345 persons with MS and 174 controls completed questionnaires regarding demographic and clinical information and underwent assessments of physical and cognitive function including the SPPB, 6-Minute Walk, Timed 25-Foot Walk, Symbol Digit Modalities Test, California Verbal Learning Test-Second Edition, and Brief Visuospatial Memory Test-Revised. Results The two-way ANOVA indicated a main effect of MS status (F(5,500)=34.74, pF(1,500)=3.88, pF(5,500)=1.20, p=.31, η2=0.012) on SPPB scores. The bivariate correlation analysis indicated that summary SPPB scores were associated with component SPPB scores in the overall samples of persons with MS (rs=0.71 to 0.83) and controls (rs=0.42 to 0.91) as well as within most age groups of MS (rs=0.63 to 0.91) and controls (rs=0.34 to 1.00). The associations between SPPB scores and physical function outcomes were larger in the sample of persons with MS (rs=–0.72 to 0.76) than controls (rs=–0.47 to 0.48). SPPB scores were further significantly associated with scores on cognitive outcomes in persons with MS (rs=0.31 to 0.43), whereas these associations were weaker in controls (rs=0.09 to 0.32). Overall, the associations between SPPB scores and physical function outcomes were stronger than the associations between SPPB scores and cognitive function outcomes. Conclusion Overall, MS status and aging have additive effects on physical function, and the summary SPPB score may be driven by a specific component within each age group. SPPB scores may be driven more by mobility rather than cognition, and are consistent with cognitive-motor coupling in MS. The novelty of this study provides evidence of worsening physical function based on the application of the SPPB and its scores across the lifespan in persons with MS and controls, and this has important implications particularly given the increasing prevalence of older adults with 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 \u3c 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

Clinical Study Oxygen Cost of Walking in Persons with Multiple Sclerosis: Disability Matters, but Why?

Background. The oxygen cost (O 2 cost) of walking is elevated in persons with MS, particularly as a function of increasing disability status. Objective. The current study examined symptomatic (i.e., fatigue, pain, anxiety, and depression) and gait (i.e., velocity, cadence, and step length) variables that might explain why disability status is associated with O 2 cost of walking in persons with MS. Materials and Methods. 82 participants completed the Patient-Determined Disease Steps, Fatigue Severity Scale, McGill Pain Questionnaire, and Hospital Anxiety and Depression Scale and undertook 2 trials of walking on a GAITRite electronic walkway. Participants then completed a six-minute walk test with concurrent assessment of expired gases for quantifying oxygen consumption and O 2 cost of walking. Results. Disability ( = 0.55) as well as fatigue ( = 0.22), gait velocity ( = −0.62), cadence ( = −0.73), and step length ( = −0.53) were associated with the O 2 cost of walking. Cadence ( = −0.67), but not step length ( = −0.14) or fatigue ( = −0.10), explained the association between disability and the O 2 cost of walking. Conclusions. These results highlight cadence as a target of rehabilitation for increasing metabolic efficiency during walking among those with MS, particularly as a function of worsening disability

Phase-III, Randomized Controlled Trial of the Behavioral Intervention for Increasing Physical Activity in Multiple Sclerosis: Project BIPAMS

Background We propose a phase-III, randomized controlled trial (RCT) that examines the effectiveness of a behavioral intervention based on social cognitive theory (SCT) and delivered through the Internet using e-learning approaches for increasing physical activity and secondary outcomes (e.g., symptoms) in a large sample of people with multiple sclerosis (MS) residing throughout the United States. Methods/design The proposed phase-III trial will use a parallel group, RCT design that examines the effect of a 6-month behavioral intervention for increasing physical activity and secondarily improving mobility, cognition, symptoms, and quality of life (QOL) in persons with MS. The primary outcome is accelerometer-measured moderate-to-vigorous physical activity (MVPA). The secondary outcomes include self-report measures of physical activity, walking impairment, cognition, fatigue, depression, anxiety, pain, sleep quality, and QOL. The tertiary outcomes are mediator variables based on SCT. Participants (N = 280) will be randomized into behavioral intervention (n = 140) or attention and social contact control (n = 140) conditions using computerized random numbers with concealed allocation. The conditions will be administered over 6-months by persons who are uninvolved in screening, recruitment, random assignment, and outcome assessment. There will be a 6-month follow-up without intervention access/content. We will collect primary, secondary, and tertiary outcome data every 6 months over the 12-month period. Data analysis will involve intent-to-treat principles and latent growth modeling (LGM). Discussion The proposed research will provide evidence for the effectiveness of a novel, widely scalable approach for increasing lifestyle physical activity and improving secondary outcomes and QOL in persons with MS

The impact of the COVID-19 pandemic on an international rehabilitation study in MS: the CogEx experience

Pandemic restrictions have led to changes in therapy plans and disrupted rehabilitation services for people with multiple sclerosis. CogEx is an international, multicentre MS dual-intervention (cognitive rehabilitation, aerobic exercise) randomized, controlled rehabilitation trial confined to people with progressive disease. The primary outcome is cognition (processing speed).There are 11 treatment sites in six countries with participants required to make 27 site visits over 12 weeks. Collectively, the large, in-person demands of the trial, and the varying international policies for the containment of COVID-19, might disproportionately impact the administration of CogEx. During the first lockdown, all centres closed on average for 82.9 (SD = 24.3) days. One site was required to lockdown on two further occasions. One site remained closed for 16 months. Ten staff (19.2%) were required to quarantine and eight staff (15.4%) tested positive for COVID. 10 of 264 (3.8%) participants acquired COVID-19. All survived. The mean duration of enrollment delay has been [236.7 (SD = 214.5) days]. Restarting participants whose interventions were interrupted by the pandemic meant recalculating the intervention prescriptions for these individuals. While the impact of the pandemic on CogEx has been considerable, all study sites are again open. Participants and staff have shown considerable flexibility and resilience in keeping a complex, international endeavour running. The future in general remains uncertain in the midst of a pandemic, but there is cautious optimism the study will be completed with sufficient sample size to robustly evaluate our hypothesis and provide meaningful results to the MS community on the impact of these interventions on people with progressive MS. Trial registration: The trial was registered on September 20th 2018 at www.clinicaltrials.gov having identifier NCT03679468. Registration was performed before recruitment was initiated

Correlates of Processing Speed Change With Combined Cognitive Rehabilitation and Exercise in Progressive MS: Secondary Analysis of the CogEx Trial

Background: Cognitive rehabilitation and exercise training are promising approaches for improving cognition in persons with progressive multiple sclerosis (MS). Identifying heterogeneity of change and factors that influence the effects of cognitive rehabilitation and/or exercise training on cognitive outcomes at the individual level have direct relevance for developing tailored and optimized rehabilitation interventions for improving cognition in progressive MS. Objective: This study involved a secondary data analysis from the CogEx trial in progressive MS. This study first described heterogeneity of change in cognitive processing speed (CPS) across the intervention conditions and then identified possible adherence/compliance, baseline performance, and demographic/clinical variables as correlates of rehabilitation-related CPS changes. Methods: A total of 311 persons with progressive MS who were pre-screened for impaired CPS completed 12 weeks of combined cognitive rehabilitation (or sham) and exercise training (or sham). CPS was measured before and after the 12-week period. As potential correlates of CPS changes, we measured adherence/compliance (ie, treatment exposure), performance outcomes at baseline, as well as demographic and clinical characteristics at baseline. Results: There was heterogeneity of change in CPS across the 4 intervention conditions. We further identified baseline learning and memory impairment and premorbid intelligence quotient (IQ), but not adherence/compliance, other baseline performance outcomes, or demographic/clinical characteristics as significant correlates of CPS changes across the 4 intervention conditions. Conclusions: The overall pattern of results suggests that future trials in this area might account for impaired learning and memory and/or premorbid IQ as potential covariates, or more carefully consider the role of reserve within rehabilitation interventions in progressive MS

The relationship between processing speed and verbal and non-verbal new learning and memory in progressive multiple sclerosis

Objective: Processing speed (PS) deficits are the most common cognitive deficits in multiple sclerosis (MS), followed by learning and memory deficits, and are often an early cognitive problem. It has been argued that impaired PS is a primary consequence of MS, which in turn decreases learning. The current analysis examined the association between PS and learning in a large cohort of individuals with progressive MS. Methods: Baseline data from a randomized clinical trial on rehabilitation taking place at 11 centers across North America and Europe were analyzed. Participants included 275 individuals with clinically definite progressive MS (primary, secondary) consented into the trial. Results: Symbol Digit Modalities Test (SDMT) significantly correlated with California Verbal Learning Test-II (CVLT-II) (r = 0.21, p = 0.0003) and Brief Visuospatial Memory Test–Revised (BVMT-R) (r = 0.516, p < 0.0001). Receiver operating characteristic (ROC) analysis of the SDMT z score to distinguish between impaired and non-impaired CVLT-II performance demonstrated an area under the curve (AUC) of 0.61 (95% confidence interval (CI): 0.55–0.68) and a threshold of −1.62. ROC analysis between SDMT and BVMT-R resulted in an AUC of 0.77 (95% CI: 0.71–0.83) and threshold of −1.75 for the SDMT z score to predict impaired BVMT-R. Conclusion: Results indicate little ability beyond chance to predict CVLT-II from SDMT (61%), albeit statistically significant. In contrast, there was a 77% chance that the model could distinguish between impaired and non-impaired BVMT-R. Several potential explanations are discussed