Objective: Examine factors underlying aerobic capacity in prodromal and manifest Huntington disease (HD) and matched controls

Background: HD results in motor impairments, weight loss, muscle weakness and wasting. While exercise training may be beneficial, it is important to understand factors underlying aerobic capacity

Method: We examined 10 pHD (mean= 43.2y), 10 mHD (mean = 52.5y), and 8 controls (mean = 46.6y). Aerobic capacity was measured with the cardiopulmonary exercise test (CPET) on a recumbent cycle ergometer. Primary outcomes were oxygen consumption (VO2), heart rate and workload. Body composition was measured using Bioelectrical Impedance Analysis and lean body mass was determined. In vivo muscle oxygen uptake was measured in the vastus lateralis with Near Infra-Red Spectroscopy. Primary outcome was change in deoxyhemoglobin (DMOx)from rest to peak exercise. Disease burden was measured with the CAP score (based on CAG repeat length and age). Motor impairment was measured with the Unified Huntington Disease Rating Scale (UHDRS). Demographic and clinical measures across groups were analyzed with One-way ANOVA. VO2, heart rate and workload were analyzed with factorial ANOVA. Regression analysis was used to examine if lean body mass, motor impairment and muscle deoxygenation were related to aerobic capacity, after adjusting for age.

Results: Age, height, weight, and lean body mass were similar across groups (p>0.05). During the CPET, peak VO2 was lower in prodromal HD (p<0.01) and peak VO2, heart rate and workload were reduced in manifest HD (p<0.05). Differences in VO2 were accentuated in prodromal and manifest HD at exercise intensity ≥ 75%. DMOxwas lower in prodromal and manifest HD (p<0.03) than controls at peak exercise. UHDRS motor score (p=0.006) and DMOx(p=0.008) were predictive of aerobic capacity, after adjusting for age.

Conclusion: Aerobic capacity is reduced in prodromal HD due to lower VO2. In manifest HD, aerobic capacity was reduced due to lower VO2, heart rate and workload. Reduced aerobic capacity in prodromal and manifest HD were accentuated at high exercise intensities. Motor impairments and reduced muscle oxygen uptake were predictive of aerobic capacity. Our results suggest that exercise training at an intensity less than 75% of peak may prevent exacerbation of muscle oxidative deficits in people with HD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/factors-underlying-reduced-aerobic-capacity-in-huntington-disease/