Abstract
Huntington’s disease (HD) is characterized by motor, cognitive, and psychiatric dysfunction. HD progression causes loss of automaticity, such that previously automatic tasks require greater attentional resources. Dual-task (DT) paradigms and fast-paced gait may stress the locomotor system, revealing deficits not seen under single-task (ST). However, the impact of gait “stress tests” on HD individuals needs further investigation. Therefore, the aims of this study were to investigate whether: 1) fast-paced and dual-task walking uncover deficits in gait and turning not seen under single-task, 2) cognitive and gait outcomes relate to fall incidence, and 3) gait deficits measured with wearable inertial sensors correlate with motor symptom severity in HD as measured by the Unified Huntington’s disease Rating Scale-total motor score (UHDRS-TMS). Seventeen HD (55 ± 9.7 years) and 17 age-matched controls (56.5 ± 9.3 years) underwent quantitative gait testing via a 25m, two-minute walk test with APDMTM inertial sensors. Gait was assessed under a 1) ST, self-selected pace, 2) fast-as-possible (FAP) pace, and 3) verbal fluency DT. The UHDRS-TMS and a cognitive test battery were administered, and a retrospective fall history was obtained. During ST, DT, and FAP conditions, HD participants demonstrated slower gait, shorter stride length, and greater lateral step and stride length variability compared to controls (p<0.00001 to 0.034). Significant dual-task costs (DTC) were observed for turns; HD participants took more time (p = 0.013) and steps (p = 0.028) to complete a turn under DT compared to controls. Higher UHDRS-TMS correlated with greater stride length variability, less double-support, and more swing-phase time under all conditions. Decreased processing speed was associated with increased gait variability under ST and FAP conditions. Unexpectedly, participant’s self-reported falls did not correlate with any gait or turn parameters. HD participants demonstrated significantly greater DTC for turning, which is less automatic than straight walking, requiring coordination of body segments, anticipatory control, and cortical regulation. Turn complexity likely makes it more susceptible to cognitive interference in HD.
Highlights
Huntington’s disease (HD) is an autosomal dominant, neurodegenerative disease caused by an expanded CAG repeat ( 40 repeats, full-penetrance) in the gene for the huntingtin protein (HTT), though symptoms may occur in some with CAG repeat lengths 36 [1]
The expansion results in aggregation of insoluble mutant HTT in neurons, the most vulnerable being striatal medium spiny neurons (MSNs) of the basal ganglia [2]
Eight HD participants were characterized as having a mixed phenotype, 4 as choreatic, and 4 as hypokinetic-rigid, one participant did not have a UHDRS-TMS recorded
Summary
Huntington’s disease (HD) is an autosomal dominant, neurodegenerative disease caused by an expanded CAG repeat ( 40 repeats, full-penetrance) in the gene for the huntingtin protein (HTT), though symptoms may occur in some with CAG repeat lengths 36 (reduced penetrance range) [1]. The expansion results in aggregation of insoluble mutant HTT (mHTT) in neurons, the most vulnerable being striatal medium spiny neurons (MSNs) of the basal ganglia [2]. The proteinaceous aggregates disrupt neuronal function, causing cell death and subsequent motor dysfunction [3]. In addition to motor symptoms, cognitive deficits observed in HD make it difficult to focus on a task or divide one’s attention between tasks. Individuals with HD have difficulty responding to multiple stimuli simultaneously [5,6], which can exacerbate motor deficits
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
