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

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

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

The Role of Premotor Areas in Dual Tasking in Healthy Controls and Persons With Multiple Sclerosis: An fNIRS Imaging Study

Persons with multiple sclerosis (pwMS) experience declines in physical and cognitive abilities and are challenged by dual-tasks. Dual-tasking causes a drop in performance, or what is known as dual-task cost (DTC). This study examined DTC of walking speed (WS) and cognitive performance (CP) in pwMS and healthy controls (HCs) and the effect of dual-tasking on cortical activation of bilateral premotor cortices (PMC) and bilateral supplementary motor area (SMA). Fourteen pwMS and 14 HCs performed three experimental tasks: (1) single cognitive task while standing (SingCog); (2) single walking task (SingWalk); and (3) dual-task (DualT) that included concurrent performance of the SingCog and SingWalk. Six trials were collected for each condition and included measures of cortical activation, WS and CP. WS of pwMS was significantly lower than HC, but neuropsychological (NP) measures were not significantly different. pwMS and HC groups had similar DTC of WS, while DTC of CP was only significant in the MS group; processing speed and visual memory predicted 55% of this DTC. DualT vs. SingWalk recruited more right-PMC activation only in HCs and was associated with better processing speed. DualT vs. SingCog recruited more right-PMC activation and bilateral-SMA activation in both HC and pwMS. Lower baseline WS and worse processing speed measures in pwMS predicted higher recruitment of right-SMA (rSMA) activation suggesting maladaptive recruitment. Lack of significant difference in NP measures between groups does not rule out the influence of cognitive factors on dual-tasking performance and cortical activations in pwMS, which might have a negative impact on quality of life

Evidence for the different physiological significance of the 6- and 2-minute walk tests in multiple sclerosis

<p>Abstract</p> <p>Background</p> <p>Researchers have recently advocated for the 2-minute walk (2MW) as an alternative for the 6-minute walk (6MW) to assess long distance ambulation in persons with multiple sclerosis (MS). This recommendation has not been based on physiological considerations such as the rate of oxygen consumption (V·O₂) over the 6MW range.</p> <p>Objective</p> <p>This study examined the pattern of change in V·O₂over the range of the 6MW in a large sample of persons with MS who varied as a function of disability status.</p> <p>Method</p> <p>Ninety-five persons with clinically-definite MS underwent a neurological examination for generating an Expanded Disability Status Scale (EDSS) score, and then completion of the 6MW protocol while wearing a portable metabolic unit and an accelerometer.</p> <p>Results</p> <p>There was a time main effect on V·O₂during the 6MW (<it>p </it>= .0001) such that V·O₂increased significantly every 30 seconds over the first 3 minutes of the 6MW, and then remained stable over the second 3 minutes of the 6MW. This occurred despite no change in cadence across the 6MW (<it>p </it>= .84).</p> <p>Conclusions</p> <p>The pattern of change in V·O₂indicates that there are different metabolic systems providing energy for ambulation during the 6MW in MS subjects and steady state aerobic metabolism is reached during the last 3 minutes of the 6MW. By extension, the first 3 minutes would represent a test of mixed aerobic and anaerobic work, whereas the second 3 minutes would represent a test of aerobic work during walking.</p

Mobility, Balance and Falls in Persons with Multiple Sclerosis

BACKGROUND: There is a lack of information concerning the relation between objective measures of gait and balance and fall history in persons with MS (PwMS). This investigation assessed the relation between demographic, clinical, mobility and balance metrics and falls history in persons with multiple sclerosis (MS). METHODS: 52 ambulatory persons with MS (PwMS) participated in the investigation. All persons provided demographic information including fall history over the last 12 months. Disease status was assessed with Expanded Disability Status Scale (EDSS). Walking speed, coordination, endurance and postural control were quantified with a multidimensional mobility battery. RESULTS: Over 51% of the participants fell in the previous year with 79% of these people being suffering recurrent falls. Overall, fallers were older, had a greater prevalence of assistive devices use, worse disability, decreased walking endurance, and greater postural sway velocity with eyes closed compared to non-fallers. Additionally, fallers had greater impairment in cerebellar, sensory, pyramidal, and bladder/bowel subscales of the EDSS. CONCLUSIONS: The current observations suggest that PwMS who are older, more disabled, utilize an assistive device, have decreased walking coordination and endurance and have diminished balance have fallen in the previous year. This suggests that individuals who meet these criteria need to be carefully monitored for future falls. Future research is needed to determine a prospective model of falls specific to PwMS. Additionally, the utility of interventions aimed at reducing falls and fall risk in PwMS needs to be established