Exercise in Huntington's Disease: Current State and Clinical Significance

Mueller, S.; Petersen, Jens A.; Jung, Hans H.

doi:10.7916/tm9j-f874

Cited by 12 publications

(1 citation statement)

References 60 publications

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“…This leads to the question of whether incoherent delivery of nutrients to the brain cells could also contribute to neuronal death in Huntington’s disease, and whether reducing cardiovascular risk factors may improve outcomes. Studies on exercise in Huntington’s disease patients have shown improved cardiovascular function, 86 but longer studies with more participants are needed to draw stronger conclusions.…”

Section: Discussionmentioning

confidence: 99%

The phase coherence of the neurovascular unit is reduced in Huntington’s disease

Bjerkan,

Kobal,

Lancaster

et al. 2024

Brain Communications

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Huntington’s disease is a neurodegenerative disorder in which neuronal death leads to chorea and cognitive decline. Individuals with ≥40 cytosine–adenine–guanine repeats on the interesting transcript 15 gene develop Huntington’s disease due to a mutated huntingtin protein. While the associated structural and molecular changes are well characterized, the alterations in neurovascular function that lead to the symptoms are not yet fully understood. Recently, the neurovascular unit has gained attention as a key player in neurodegenerative diseases. The mutant huntingtin protein is known to be present in the major parts of the neurovascular unit in individuals with Huntington’s disease. However, a non-invasive assessment of neurovascular unit function in Huntington’s disease has not yet been performed. Here, we investigate neurovascular interactions in presymptomatic (N = 13) and symptomatic (N = 15) Huntington’s disease participants compared to healthy controls (N = 36). To assess the dynamics of oxygen transport to the brain, functional near-infrared spectroscopy, ECG and respiration effort were recorded. Simultaneously, neuronal activity was assessed using EEG. The resultant time series were analysed using methods for discerning time-resolved multiscale dynamics, such as wavelet transform power and wavelet phase coherence. Neurovascular phase coherence in the interval around 0.1 Hz is significantly reduced in both Huntington’s disease groups. The presymptomatic Huntington’s disease group has a lower power of oxygenation oscillations compared to controls. The spatial coherence of the oxygenation oscillations is lower in the symptomatic Huntington’s disease group compared to the controls. The EEG phase coherence, especially in the α band, is reduced in both Huntington’s disease groups and, to a significantly greater extent, in the symptomatic group. Our results show a reduced efficiency of the neurovascular unit in Huntington’s disease both in the presymptomatic and symptomatic stages of the disease. The vasculature is already significantly impaired in the presymptomatic stage of the disease, resulting in reduced cerebral blood flow control. The results indicate vascular remodelling, which is most likely a compensatory mechanism. In contrast, the declines in α and γ coherence indicate a gradual deterioration of neuronal activity. The results raise the question of whether functional changes in the vasculature precede the functional changes in neuronal activity, which requires further investigation. The observation of altered dynamics paves the way for a simple method to monitor the progression of Huntington’s disease non-invasively and evaluate the efficacy of treatments.

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Section: Discussionmentioning

confidence: 99%

The phase coherence of the neurovascular unit is reduced in Huntington’s disease

Bjerkan,

Kobal,

Lancaster

et al. 2024

Brain Communications

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

Playle

Dimitropoulou

Kelson

et al. 2019

Movement Disord Clin Pract

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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.

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Cognition-oriented treatments and physical exercise on cognitive function in Huntington’s disease: a systematic review

et al. 2022

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Exercise in Huntington's Disease: Current State and Clinical Significance

Cited by 12 publications

References 60 publications

The phase coherence of the neurovascular unit is reduced in Huntington’s disease

The phase coherence of the neurovascular unit is reduced in Huntington’s disease

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

Cognition-oriented treatments and physical exercise on cognitive function in Huntington’s disease: a systematic review

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