Remotely-delivered exercise training program for improving physical and cognitive functions among older adults with multiple sclerosis: Protocol for an NIH stage-I randomized controlled trial.

BACKGROUND: Older adults with multiple sclerosis (MS) present with low physical activity participation, cognitive and ambulatory dysfunctions, and compromised quality of life (QOL). OBJECTIVE: We propose a NIH Stage-I, randomized controlled trial (RCT) that examines the feasibility and efficacy of a 16-week theory-based, remotely-delivered, exercise training program for improving cognitive and physical functions in older adults with MS who have moderate mobility disability without severe cognitive impairment. METHODS: This Stage-I study utilizes a parallel-group RCT design. Participants (N = 50; age ≥ 50 years) will be randomly assigned into exercise training (combined aerobic and resistance exercise) or active control (flexibility and stretching) conditions. The conditions will be undertaken within a participant's home/community over a 16-week period, and monitored remotely and supported by Zoom-based chats guided by social cognitive theory (SCT) via a behavioral coach. Participants will receive training manuals and equipment, one-on-one behavioral coaching, action-planning calendars, self-monitoring logs, and SCT-based newsletters. The primary outcomes include feasibility (e.g., recruitment and retention rates), exercise behavior and physical activity; other outcomes include physical function (lower-extremity function, mobility, walking), cognition (processing speed, learning and memory, executive function), MS symptoms, QOL, and vascular function. We will collect outcome data at baseline (Week 0), post-intervention (Week 16), and follow-up (Week-32). Data analysis will follow intent-to-treat principles using linear mixed-effects models. DISCUSSION: This Stage-I trial adopts an innovative approach for exercise training via telerehabilitation and is convenient and accessible for older adults with MS. If successful, the study will provide foundations for future research using remotely-delivered exercise intervention for managing the consequences of aging with MS. TRIAL REGISTRATION NUMBER: NCT05930821.

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.

Systematic review and meta-analysis of sedentary behavior in persons with multiple sclerosis.

BACKGROUND: Persons with multiple sclerosis (MS) engage in less physical activity than the general population, and the disease manifestations and comorbidity conditions might further predispose them toward sedentary behavior (SB) among this population. We performed a systematic review with meta-analysis of studies that compared SB in persons with MS and non-MS controls, and examined factors that may moderate the difference in SB between the two groups. METHODS: We conducted a systematic search using PubMed, PsycINFO, Scopus, and CINAHL from inception up to August 2022, and identified studies that involved group comparison of SB outcomes between MS and non-MS controls. Effect sizes were calculated as standardized mean differences (SMDs) using Hedge's g. We generated a multilevel random-effects model for estimating an overall effect, and performed moderator analyses. Methodological quality was assessed using the Appraisal Tool for Cross-Sectional Studies (AXIS tool). RESULTS: Eleven studies were included (1403 MS vs. 449 controls) and yielded 17 effects for meta-analysis. Results indicated an overall small, but significant effect (SMD [95% CI] = 0.27 [0.02, 0.53], p = 0.03) with significant heterogeneity (Q16 = 72.2, p < 0.01; I2total = 75.8%). There were larger effects when the MS sample had a higher proportion of females, or when SB was reported as percent sedentary time per day compared with other SB outcomes (p = 0.03 and 0.05, respectively). The included studies achieved fairly good quality (91.4%) using the AXIS tool. CONCLUSIONS: The cumulative evidence supports that persons with MS engage in more SB than non-MS controls. Our findings may support the design of targeted behavioral change interventions for reducing SB and improving health and function in the MS population.

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.

Vascular dysfunction in multiple sclerosis: Scoping review of current evidence for informing future research directions.

BACKGROUND: The research involving vascular comorbidity in people with multiple sclerosis (MS) could be advanced through investigations applying measurements of vascular function such as pulse wave velocity or flow mediated dilation as mechanistic endpoints in the study of physical comorbidity management in MS across the lifespan. We conducted a scoping review of research on vascular function parameters and outcomes in MS and developed a research agenda for future inquiry. METHODS: We searched PubMed from inception through February 2023 for articles involving relevant central and peripheral vascular function data or correlates of vascular function (arterial stiffness, endothelial function, blood pressure parameters, etc.) in conjunction with relevant outcomes (walking function, cognition, etc.) in MS. Studies were limited to English-language and primary research articles. RESULTS: Our search and subsequent screening identified 10 relevant articles. Four papers focused on arterial stiffness and reported pulse wave velocity and arterial compliance in MS compared with controls. Two papers focused on endothelial function and reported flow-mediated dilation in MS compared with controls. There was evidence that arterial stiffness and endothelial function were associated with cognition and disease progression in MS, respectively. One paper reported that physical activity was associated with arterial stiffness in MS. There was one protocol paper examining the effect of a home-based exercise program on markers of subclinical atherosclerosis; however, the results are unpublished, and there was no literature beyond this surrounding the impact of lifestyle behavior (e.g., diet) or exercise interventions on vascular function. CONCLUSION: There is emerging evidence for vascular dysfunction in MS, and this is associated with cognition and disease progression; we know very little about approaches for managing vascular dysfunction in MS. To that end, we offer an agenda for research on measurements and outcomes of vascular function in relation to MS and disease attributes, along with proposed mechanisms and lifestyle changes that could aid in managing vascular dysfunction.

Head Trauma not Associated with Long Term Effects on Autonomic Function.

Contact-sports can elicit concussions, which impacts autonomic function, as well as elicit repetitive head trauma, where autonomic function has not yet been assessed. The purpose of this study was to determine if differences in autonomic function exist among three groups (CTRL: healthy non-contact-sport participant, RHT: repetitive head trauma contact-sport participant, CONC: previous concussion). Forty participants (16 men and 24 women), aged 18-37 (22 ± 3), participated in the study. Participants were grouped based on their sport and concussion history (CTRL, RHT, and CONC). Body composition was measured via air displacement plethysmography. Prior to testing, participants were outfitted with equipment to evaluate heart rate, blood pressure, and cerebral-artery blood flow velocity (CBFv). The participant performed against three stimuli: deep breathing, Valsalva maneuver, and a 70° head-up tilt test. Following autonomic function testing, a YMCA submaximal cycle test was performed. All group comparisons were analyzed using a one-way ANOVA and all data are presented as means ± standard deviation. The results of this study indicated that the groups did not differ in respiratory sinus arrhythmia (CTRL: 22 ± 6 bpm, RHT: 21 ± 8 bpm, CONC: 19 ± 7 bpm, p = 0.471), Valsalva ratio (CTRL: 2.19 ± 0.39, RHT: 2.09 ± 0.37, CONC: 2.00 ± 0.47, p = 0.519), CBFv (CTRL: 47.74 ± 25.28 cm/s, RHT: 40.99 ± 10.93 cm/s, CONC: 43.97 ± 17.55 cm/s, p = 0.657), or tilt time (CTRL: 806.09 ± 368.37 sec, RHT: 943.07 ± 339.54 sec, CONC: 978.40 ± 387.98 sec, p = 0.479). However, CONC (113.24 ± 11.64 mmHg) had a significantly higher mean systolic blood pressure during the tilt test than CTRL (102.66 ± 7.79 mmHg, p = 0.026), while RHT (107.9 ± 9.0 mmHg) was not significantly different than CTRL (p = 0.39) or CONC (p = 0.319). The results of this study are the first step in determining if long-lasting deficits to the autonomic nervous system occur following a diagnosis of concussion. However, concussions do not seem to have lasting effects on autonomic function. Overwhelmingly, dysautonomia is not present during chronic recovery from concussions or in individuals with RHT from contact-sports. In the future, sex should be considered as a variable.