Exercise Interventions in Huntington's Disease: An Individual Patient Data Meta‐Analysis

Abstract

Background Physical activity may be beneficial in Huntington's disease (HD); however, studies to date have been underpowered to detect change. We combined data from five randomized controlled feasibility trials using individual patient data meta‐analyses. Methods/Design All trial interventions comprised a combination of supervised and self‐directed physical activity, with varied emphasis on aerobic, strength, endurance, flexibility, and task training. Duration ranged from 8 to 16 weeks. The primary outcome was the modified Unified Huntington's Disease Rating Motor Score. Secondary outcomes included the Symbol Digit Modality Test, Berg Balance Scale, 30‐second Chair stand, Timed Up and Go, Gait Speed, Physical Performance Test, Six‐Minute Walk, International Physical Activity Questionnaire, Hospital Anxiety and Depression Scale, EuroQol Health Utility Index, and Short‐Form 36 Health Related Quality of Life Scale. The primary analysis utilized a two‐stage approach. A one‐stage approach was explored as a sensitivity analysis using a cross‐classified (by study site) linear mixed‐effects model. Results One hundred twenty‐one participants provided complete data. Risk of bias was moderate; however, primary outcomes were blind assessed. Primary pooled effect estimates adjusted for baseline modified motor score (95% confidence interval) were 0.2 (–2.1 to 2.6) favoring control. There was considerable heterogeneity between the studies. Conclusions There was no evidence of an exercise effect on the modified motor score in these relatively short‐duration interventions. Longer‐duration trials incorporating supervised components meeting frequency, intensity, time, and type principles are required. Lack of common outcomes limited the analysis and highlight the importance of a core outcome set for evaluating exercise in HD.

Motor Cortex Plasticity Response to Acute Cardiorespiratory Exercise and Intermittent Theta-Burst Stimulation is Attenuated in Premanifest and Early Huntington’s Disease

“…These ndings have important implications for studies of exercise in HD, as attenuated brain responses to exercise may contribute to the mixed outcomes reported for exercise interventions in HD to date. Although some non-randomized controlled trials of exercise interventions have reported promising results, a recent meta-analysis of motor and cognitive effects from randomized controlled trials indicated no signi cant effects from the interventions on either the primary outcome (UHDRS motor score) or secondary outcomes (cognitive, health status or physical) 11 . The current ndings indicate that more research is urgently needed to understanding under what circumstances exercise may elicit an optimal neurophysiological response in HD (e.g., by investigating response to different types of exercise, or if there are effects over the longer-term following multiple exercise sessions), to inform the future direction of exercise intervention research in this population.…”

“…Additionally, one retrospective study of people with HD found that a lifestyle comprising less passive activity was associated with later disease onset 9 . Recently, a number of exercise interventions have been trialed in HD with mixed results [10][11][12][13] , although one study provided preliminary evidence that a 9 month multidisciplinary intervention that included exercise increased grey matter volume and improved learning and memory 13 . One of the key obstacles to designing effective exercise interventions in HD is the lack of clarity regarding the mechanisms that underlie the effect of exercise in people with the HD gene.…”

Motor cortex plasticity response to acute cardiorespiratory exercise and intermittent theta-burst stimulation is attenuated in premanifest and early Huntington’s disease

“…These findings have important implications for studies of exercise in HD, as attenuated brain responses to exercise may contribute to the mixed outcomes reported for exercise interventions in HD to date. Although some non-randomized controlled trials of exercise interventions have reported promising results, a recent meta-analysis of motor and cognitive effects from randomized controlled trials indicated no significant effects from the interventions on either the primary outcome (UHDRS motor score) or secondary outcomes (cognitive, health status or physical) 11 . The current findings indicate that more research is urgently needed to understand under what circumstances exercise may elicit an optimal neurophysiological response in HD (e.g., by investigating response to different types of exercise, or if there are effects over the longer-term following multiple exercise sessions), to inform the future direction of exercise intervention research in this population.…”

Home-Based Exercise to Improve Motor Functions, Cognitive Functions, and Quality of Life in People with Huntington’s Disease: A Systematic Review and Meta-Analysis

“…Despite these data regarding the effectiveness of exercise interventions, the results of the previous systematic reviews and meta-analyses are controversial. For example, Playle R et al (2019) concluded that there is no evidence of an exercise effect on the UHDRS motor scores [ 33 ]. However, Fritz NE (2017) reported a beneficial effect of exercise and physical activity interventions in HD concerning motor function [ 7 ].…”