Vigorous cool room treadmill training to improve walking ability in people with multiple sclerosis who use ambulatory assistive devices: a feasibility study.

BACKGROUND: Aerobic training has the potential to restore function, stimulate brain repair, and reduce inflammation in people with Multiple Sclerosis (MS). However, disability, fatigue, and heat sensitivity are major barriers to exercise for people with MS. We aimed to determine the feasibility of conducting vigorous harness-supported treadmill training in a room cooled to 16 °C (10 weeks; 3times/week) and examine the longer-term effects on markers of function, brain repair, and inflammation among those using ambulatory aids. METHODS: Ten participants (9 females) aged 29 to 74 years with an Expanded Disability Status Scale ranging from 6 to 7 underwent training (40 to 65% heart rate reserve) starting at 80% self-selected walking speed. Feasibility of conducting vigorous training was assessed using a checklist, which included attendance rates, number of missed appointments, reasons for not attending, adverse events, safety hazards during training, reasons for dropout, tolerance to training load, subjective reporting of symptom worsening during and after exercise, and physiological responses to exercise. Functional outcomes were assessed before, after, and 3 months after training. Walking ability was measured using Timed 25 Foot Walk test and on an instrumented walkway at both fast and self-selected speeds. Fatigue was measured using fatigue/energy/vitality sub-scale of 36-Item Short-Form (SF-36) Health Survey, Fatigue Severity Scale, modified Fatigue Impact Scale. Aerobic fitness (maximal oxygen consumption) was measured using maximal graded exercise test (GXT). Quality-of-life was measured using SF-36 Health Survey. Serum levels of neurotrophin (brain-derived neurotrophic factor) and cytokine (interleukin-6) were assessed before and after GXT. RESULTS: Eight of the ten participants completed training (attendance rates ≥ 80%). No adverse events were observed. Fast walking speed (cm/s), gait quality (double-support (%)) while walking at self-selected speed, fatigue (modified Fatigue Impact Scale), fitness (maximal workload achieved during GXT), and quality-of-life (physical functioning sub-scale of SF-36) improved significantly after training, and improvements were sustained after 3-months. Improvements in fitness (maximal respiratory exchange ratio and maximal oxygen consumption during GXT) were associated with increased brain-derived neurotrophic factor and decreased interleukin-6. CONCLUSION: Vigorous cool room training is feasible and can potentially improve walking, fatigue, fitness, and quality-of-life among people with moderate to severe MS-related disability. TRIAL REGISTRATION: The study was approved by the Newfoundland and Labrador Health Research Ethics Board (reference number: 2018.088) on 11/07/2018 prior to the enrollment of first participant (retrospectively registered at ClinicalTrials.gov: NCT04066972. Registered on 26 August 2019.

Task-Oriented Circuit Training as an Alternative to Ergometer-Type Aerobic Exercise Training after Stroke.

Moderate-intensity aerobic exercise training is an important treatment strategy to enhance functional recovery and decrease cardiometabolic risk factors after stroke. However, stroke related impairments limit access to ergometer-type exercise. The aims of the current study were (1) to evaluate whether our task-oriented circuit training protocol (intermittent functional training; IFT) could be used to sustain moderate-intensity aerobic workloads over a 10-week intervention period, and (2) to investigate its preliminary effects on cardiorespiratory fitness and metabolic profiles compared to constant-load ergometer-type exercise (CET). Forty chronic hemiparetic stroke survivors were randomized to receive 30 sessions of IFT or CET over ten weeks. Similar proportions of participants were randomized to IFT (7/19) and CET (9/18) sustained workloads associated with moderate-intensity aerobic exercise over the study period (p = 0.515). However, CET was associated with more substantial changes in maximal oxygen uptake (MD = 2.79 mL min-1 kg-1 CI: 0.84 to 4.74) compared to IFT (MD = 0.62 mL min-1 kg-1 CI: -0.38 to 1.62). Pre to post changes in C-reactive protein (-0.9 mg/L; p =0.017), short-term glycemia (+14.7 mol/L; p = 0.026), and resting whole-body carbohydrate oxidation (+24.2 mg min-1; p = 0.046) were observed when considering both groups together. Accordingly, IFT can replicate the aerobic intensities sustained during traditional ergometer-type exercise training. More work is needed to evaluate the dose-response effects of such task-oriented circuit training protocols on secondary prevention targets across the continuum of stroke recovery.

Under-treated depression negatively impacts lifestyle behaviors, participation and health-related quality of life among older people with multiple sclerosis.

PURPOSE: To what extent depression may negatively impact successful aging with multiple sclerosis (MS) is not known. We examined the impact of depression/depressive symptoms on lifestyle choices (diet, exercise, smoking and alcohol), participation and health-related quality of life (HRQoL) among older people living with MS (n = 742). METHODS: Based on self-reported depression diagnosis and scores on the Hospital Anxiety and Depression Scale, we divided the sample into four groups: 1. No depression diagnosis and low symptoms (n = 412), 2. Diagnosed with depression and low symptoms (n = 103), 3. Diagnosed with depression and high symptoms (n = 87), and 4. No depression diagnosis and high symptoms (n = 140). We used regression modelling to predict outcomes, controlling for age, MS disease duration, type of MS at initial diagnosis and disability. RESULTS: A high proportion (44.5%) reported either being diagnosed with depression, having high levels of symptoms or both. Only 12.1% reported that they were prescribed anti-depressants and 13.6% utilized psychosocial services. Compared to those with depression who had low symptoms, respondents who had high depressive symptoms (n = 227) were more likely to be non-exercisers (OR 1.85, 95%CI 1.02-3.34, p = 0.042), consume a poor diet (OR 2.12, 95%CI 1.27-3.52, p = 0.004), have the lowest levels of participation (OR 3.36, 95%CI 1.74-6.49, p = 0.0003) and report the poorest HRQoL (OR 1.95, 95%CI 1.17-3.26, p = 0.011). Men and people experiencing higher levels of disability and fatigue were at greater risk of having high symptoms and being undiagnosed. CONCLUSION: Undiagnosed and under-treated depression is common among older people living with MS and adversely impacts health choices.

Serum levels of insulin-like growth factor-1 and brain-derived neurotrophic factor as potential recovery biomarkers in stroke.

OBJECTIVES: Our objectives were: 1) to determine whether maximal aerobic exercise increased serum neurotrophins in chronic stroke and 2) to determine the factors that predict resting and exercise-dependent levels. METHODS: We investigated the potential predictors of resting and exercise-dependent serum insulin-like growth factor-1 and brain-derived neurotrophic factor among 35 chronic stroke patients. Predictors from three domains (demographic, disease burden, and cardiometabolic) were entered into 4 separate stepwise linear regression models with outcome variables: resting insulin-like growth factor, resting brain-derived neurotrophic factor, exercise-dependent change in insulin-like growth factor, and exercise-dependent change brain-derived neurotrophic factor. RESULTS: Insulin-like growth factor decreased after exercise (p = 0.001) while brain-derived neurotrophic factor did not change (p = 0.38). Greater lower extremity impairment predicted higher resting brain-derived neurotrophic factor (p = 0.004, r2 = 0.23). Higher fluid intelligence predicted greater brain-derived neurotrophic factor response to exercise (p = 0.01, r2 = 0.18). There were no significant predictors of resting or percent change insulin-like growth factor-1. DISCUSSION: Biomarkers have the potential to characterize an individual's potential for recovery from stroke. Neurotrophins such as insulin-like growth factor-1 and brain-derived neurotrophic factor are thought to be important in neurorehabilitation; however, the factors that modulate these biomarkers are not well understood. Resting brain-derived neurotrophic factor and percent change in brain-derived neurotrophic factor were related to physical and cognitive recovery in chronic stroke, albeit weakly. Insulin-like growth factor-1 was not an informative biomarker among chronic stroke patients. The novel finding that fluid intelligence positively correlated with exercise-induced change in brain-derived neurotrophic factor warrants further research.

Synergistic Benefits of Combined Aerobic and Cognitive Training on Fluid Intelligence and the Role of IGF-1 in Chronic Stroke.

BACKGROUND: Paired exercise and cognitive training have the potential to enhance cognition by "priming" the brain and upregulating neurotrophins. METHODS: Two-site randomized controlled trial. Fifty-two patients >6 months poststroke with concerns about cognitive impairment trained 50 to 70 minutes, 3× week for 10 weeks with 12-week follow-up. Participants were randomized to 1 of 2 physical interventions: Aerobic (>60% VO2peak using <10% body weight-supported treadmill) or Activity (range of movement and functional tasks). Exercise was paired with 1 of 2 cognitive interventions (computerized dual working memory training [COG] or control computer games [Games]). The primary outcome for the 4 groups (Aerobic + COG, Aerobic + Games, Activity + COG, and Activity + Games) was fluid intelligence measured using Raven's Progressive Matrices Test administered at baseline, posttraining, and 3-month follow-up. Serum neurotrophins collected at one site (N = 30) included brain-derived neurotrophic factor (BDNF) at rest (BDNFresting) and after a graded exercise test (BDNFresponse) and insulin-like growth factor-1 at the same timepoints (IGF-1rest, IGF-1response). RESULTS: At follow-up, fluid intelligence scores significantly improved compared to baseline in the Aerobic + COG and Activity + COG groups; however, only the Aerobic + COG group was significantly different (+47.8%) from control (Activity + Games -8.5%). Greater IGF-1response at baseline predicted 40% of the variance in cognitive improvement. There was no effect of the interventions on BDNFresting or BDNFresponse; nor was BDNF predictive of the outcome. CONCLUSIONS: Aerobic exercise combined with cognitive training improved fluid intelligence by almost 50% in patients >6 months poststroke. Participants with more robust improvements in cognition were able to upregulate higher levels of serum IGF-1 suggesting that this neurotrophin may be involved in behaviorally induced plasticity.