Salivary cortisol dysrhythmias have been reported in some, but not all studies assessing hypothalamic-pituitary-adrenal (HPA) axis function in Huntington's disease (HD). These differences are ...presumed to be due to environmental influences on temporal salivary cortisol measurement. Further exploration of HPA-axis function using a more stable and longer-term measure, such as hair cortisol, is needed to confirm earlier findings. This study aimed to evaluate hair and salivary cortisol concentrations and their associations with clinical and lifestyle outcomes in individuals with premanifest HD (n = 26) compared to healthy controls (n = 14). Participants provided saliva and hair samples and data were collected on clinical disease outcomes, mood, cognition, physical activity, cognitive reserve, sleep quality and social network size to investigate relationships between clinical and lifestyle outcomes and cortisol concentrations. Hair and salivary cortisol concentrations did not significantly differ between the premanifest HD and control groups. No significant associations were observed between hair or salivary cortisol concentrations and cognitive, mood or lifestyle outcomes. However, hair cortisol concentrations were significantly associated with disease outcomes in individuals with premanifest HD. Significant associations between hair cortisol concentrations and measures of disease burden and onset may suggest a potential disease marker and should be explored longitudinally in a larger sample of individuals with HD.
Background: Mass-casualty incidents (MCIs) are catastrophic. Whether they arise from natural or man-made disasters, the nature of such incidents and the multiple casualties involved can rapidly ...overwhelm response personnel. Mass-casualty triage training is traditionally taught via either didactic lectures or table top exercises. This training fails to provide an opportunity for practical application or experiential learning in immersive conditions. Further, large-scale simulations are heavily resource-intensive, logistically challenging, require the coordination and time of multiple personnel, and are costly to replicate. This study compared the simulation efficacy of a bespoke virtual-reality (VR) MCI simulation with an equivalent live simulation scenario designed for undergraduate paramedicine students. Methods: Both simulations involved ten injured patients resulting from a police car chase and shooting. Twenty-nine second-year paramedicine students completed the live and VR simulation in a random order. The training efficacy of the VR and live simulation was evaluated with respect to student immersion and task-difficulty, clinical decision-making (i.e. triage card allocation accuracy and timeliness), learning satisfaction, and cost of delivery. Results: While perceived physical demand was higher in the live simulation compared to VR (p < 0.001), no differences were observed across mental demand, temporal demand, performance, effort or frustration domains. No differences were found for participant satisfaction across the two platforms. No differences were observed in the number of triage cards correctly allocated to patients in each platform. However, participants were able to allocate cards far quicker in VR (p < .001). Cost of running the VR came to AUD $712.04 (staff time), compared to the live simulations which came to AUD $9,413.71 (staff time, moulage, actors, director, prop vehicle), approximately 13 times more expensive. Conclusion: The VR simulation provided near identical simulation efficacy for paramedicine students compared to the live simulation. VR MCI training resources represent an exciting new direction for authentic and cost-effective education and training for medical professionals.
Huntington's disease (HD) is a chronic, progressive neurodegenerative condition for which there are currently no proven disease-modifying therapies. Lifestyle factors have been shown to impact on the ...age of disease onset and progression of disease features. We therefore investigated the effects of a nine-month multidisciplinary rehabilitation intervention on neuroimaging, biological and clinical disease outcomes in individuals with premanifest HD.
31 individuals with premanifest HD participated in the study. Eighteen participants underwent a nine-month multidisciplinary rehabilitation intervention comprising aerobic and resistance exercise, computerised cognitive training, dual-task training and sleep hygiene and nutritional guidance. The remaining 13 participants were allocated to a standard care control group. Neuroimaging, biological, cognitive, motor and cardiorespiratory fitness data was collected.
Participants displayed good adherence (87%) and compliance (85%) to the intervention. Maintenance of the shape of the right putamen was observed in the intervention group when compared to the control group. The intervention group displayed significant improvements in verbal learning and memory, attention, cognitive flexibility and processing speed following the intervention when compared to the control group. Performance on the mini-social cognition and emotional assessment (mini-SEA) was maintained in the intervention group, but decreased in the control group. No changes were observed in serum neurofilament light protein levels, postural stability outcomes or cardiorespiratory fitness.
This study adds to the accumulating body of literature to suggest that multidisciplinary rehabilitation is of clinical benefit for individuals with HD. Large randomised controlled trials are necessary to determine the extent to which benefits occur across the spectrum of the disease.
•Multidisciplinary rehabilitation preserves right putamen shape in premanifest HD.•Multidisciplinary rehabilitation improves cognition in premanifest HD.•Multidisciplinary rehabilitation has no effect on serum NfL in premanifest HD.
Abstract
Objective
Dual-tasking deficiencies are common in people with Huntington disease (HD) and contribute to reduced functional independence. To date, few studies have investigated the ...determinants of dual-tasking deficiencies in this population. The reliability of dual-tasking measures has also been poorly investigated in HD. The purpose of this study was to investigate the influence of clinical determinants on dual-tasking performance and to determine the association of disease burden outcomes on dual-tasking performance in individuals with premanifest HD.
Methods
Thirty-six individuals with premanifest HD and 28 age- and sex-matched healthy controls were recruited for this study. Participants performed 3 single-task (2 cognitive and 1 motor) and 2 dual-task assessments, comprising motor (postural stability) and cognitive (simple or complex mental arithmetic) components. In addition, participants performed a comprehensive clinical battery comprising motor, cognitive, mood, and sleep assessments as well as lifestyle and disease burden measures.
Results
Poorer sleep quality was associated with greater cognitive dual-task cost in individuals with premanifest HD. Compared with healthy controls, people with premanifest HD demonstrated an impaired capacity to dual task. Dual-task measures exhibited acceptable test–retest reliability in premanifest HD and healthy control groups.
Conclusion
These results show that dual-tasking measures are sensitive and reliable in individuals with premanifest HD. Furthermore, poor sleep quality is associated with worse cognitive performance on dual tasks, which should be considered by rehabilitation specialists when examining and therapeutically managing dual-tasking problems in individuals with HD and other neurodegenerative populations in the future.
Impact
This study adds important knowledge to the sparse literature on dual-tasking deficiencies in people with HD. When examining and therapeutically managing dual-tasking problems in this and other neurodegenerative populations, rehabilitation specialists should consider that people with premanifest HD may have an impaired capacity to dual task. Clinicians also should assess sleep quality, as poorer sleep quality is associated with worse cognitive performance on dual tasks in these individuals.
Lay Summary
If you have premanifest HD and poor quality of sleep, you may pay more attention to maintaining postural stability rather than performing arithmetic calculations to reduce the risk of falling.
•An interaction between HPA-axis and sleep disturbances and BDNF in HD is proposed.•Glucocorticoids and BDNF are intricately balanced and impact on sleep architecture.•HPA-axis and sleep disturbances ...are likely to facilitate a reduction in BDNF levels.•HPA-axis, sleep and BDNF alterations could contribute to neuropathology of HD.•Multidisciplinary therapy is expected to provide an adaptive stress response in HD.
Huntington’s disease (HD) is a fatal neurodegenerative disease caused by an extended polyglutamine tract in the huntingtin protein. Circadian, sleep and hypothalamic-pituitary-adrenal (HPA) axis disturbances are observed in HD as early as 15 years before clinical disease onset. Disturbances in these key processes result in increased cortisol and altered melatonin release which may negatively impact on brain-derived neurotrophic factor (BDNF) expression and contribute to documented neuropathological and clinical disease features. This review describes the normal interactions between neurotrophic factors, the HPA-axis and circadian rhythm, as indicated by levels of BDNF, cortisol and melatonin, and the alterations in these intricately balanced networks in HD. We also discuss the implications of these alterations on the neurobiology of HD and the potential to result in hypothalamic, circadian, and sleep pathologies. Measurable alterations in these pathways provide targets that, if treated early, may reduce degeneration of brain structures. We therefore focus here on the means by which multidisciplinary therapy could be utilised as a non-pharmaceutical approach to restore the balance of these pathways.
The aim of the present study was to quantify explosive joint torque or the ability to develop joint torque rapidly, typically measured as the rate of torque development, in individuals with prodromal ...Huntington's disease and healthy controls and its associations with measures of disease burden and striatal pathology. Twenty prodromal Huntington's disease and 19 healthy control individuals volunteered for this study. Plantar flexor isometric rate of torque development values were evaluated using isokinetic dynamometry. Pathological changes in striatal shape were evaluated using magnetic resonance imaging. Disease burden was evaluated using the disease burden score and cytosine-adenine-guanine age product score. No statistical differences in the rate of torque development were observed between individuals with prodromal Huntington's disease and healthy controls. However, significant associations were observed between the rate of torque development values and measures of disease burden (r = -0.42 to -0.69) and striatal pathology (r = 0.71-0.60) in individuals with prodromal Huntington's disease. We found significant associations between lower rate of torque development values and greater striatal shape deflation and disease burden and striatal pathology in individuals with prodromal Huntington's disease. While no significant differences in the rate of torque development were found between prodromal Huntington's disease and healthy controls, the noted associations suggest that differences may emerge as the disease advances, which should be investigated longitudinally in future studies.
Hypothalamic pathology is a well-documented feature of Huntington's disease (HD) and is believed to contribute to circadian rhythm and habitual sleep disturbances. Currently, no therapies exist to ...combat hypothalamic changes, nor circadian rhythm and habitual sleep disturbances in HD.
To evaluate the effects of multidisciplinary rehabilitation on hypothalamic volume, brain-derived neurotrophic factor (BDNF), circadian rhythm and habitual sleep in individuals with preclinical HD.
Eighteen individuals with HD (ten premanifest and eight prodromal) undertook a nine-month multidisciplinary rehabilitation intervention (intervention group), which included exercise, cognitive and dual task training and social events, and were compared to a community sample of eleven individuals with premanifest HD receiving no intervention (control group). Hypothalamic volume, serum BDNF, salivary cortisol and melatonin concentrations, subjective sleep quality, daytime somnolence, habitual sleep-wake patterns, stress and anxiety and depression symptomatology were evaluated.
Hypothalamus grey matter volume loss was significantly attenuated in the intervention group compared to the control group after controlling for age, gender, Unified Huntington's Disease Rating Scale-Total Motor Score and number of cytosine-adenine-guanine repeats. Serum BDNF levels were maintained in the intervention group, but decreased in the control group following the study period. Both groups exhibited decreases in cortisol and melatonin concentrations. No changes were observed in sleep or mood outcomes.
This exploratory study provides evidence that multidisciplinary rehabilitation can reduce hypothalamic volume loss and maintain peripheral BDNF levels in individuals with preclinical HD but may not impact on circadian rhythm. Larger, randomised controlled trials are required to confirm these findings.
Poorer sleep health outcomes have been documented in the general population during the COVID-19 outbreak. However, the impact of the COVID-19 outbreak on sleep health outcomes in specific population ...groups, including the sporting community, has not been extensively investigated. This study evaluated sleep health outcomes and their relationship with lifestyle behaviours during the initial COVID-19 lockdown period in Australian community tennis players.
This cross-sectional study evaluated sleep health outcomes and lifestyle behaviours using an online survey. The survey was disseminated online between the 24th of April and the 6th of June 2020 and comprised the Sleep Health Index, Sleep Satisfaction Tool and questions regarding weekly hours of tennis play, general physical activity, training location and alcohol consumption. Two-hundred and eighty-five individuals completed the survey.
Compared to normative data, respondents displayed positive sleep health values during the initial COVID-19 lockdown period, with median values (IQR) of 85.3 (73.4, 91.7) and 64.8 (54.4, 73.4) for the Sleep Health Index and Sleep Satisfaction Tool, respectively. Sleep health outcomes were not significantly correlated (
> 0.05) with tennis play (Tb = 0.054-0.077), physical activity (Tb = -0.008 to 0.036), training location (Tb = -0.012 to -0.005) or alcohol consumption (Tb = -0.079 to -0.018).
Positive sleep health values were observed in Australian community-level tennis players during the initial COVID-19 pandemic. Sleep health values were not associated with lifestyle behaviours. Other unexplored factors may have influenced sleep health outcomes, including personal finances and socialisation, however these factors need to be investigated in future studies.
Objective
The primary objective of this trial was to evaluate the effects of outpatient multidisciplinary therapy, compared to usual care, on measures of physical function and muscle strength in ...patients with manifest Huntington's disease (HD).
Methods
Twenty‐two patients with clinically verified HD were randomized to receive 36 weeks of outpatient multidisciplinary therapy or usual care. Outpatient multidisciplinary therapy comprised 9 months of supervised exercise, cognitive therapy and self‐directed home‐based exercise. Usual care consisted of standard medical care. Patients were assessed at 0 and 36 weeks by blinded assessors. The primary outcome was changed in mobility as measured by the 10‐m Timed Walk Test. Secondary outcome measures included changes in manual dexterity (Timed Nut and Bolt Test), balance (Berg Balance Scale), cardiorespiratory endurance (6‐Minute Walk Test) and upper and lower extremity muscle strength (isokinetic and isometric muscle strength and 10 Repetition Sit‐to‐Stand Tests).
Results
Patients receiving outpatient multidisciplinary therapy demonstrated significantly enhanced manual dexterity (P < 0.05) and lower extremity muscle strength (P < 0.05) than patients receiving usual care. No significant differences in mobility, balance, cardiorespiratory endurance and upper extremity strength outcomes were observed between groups after the intervention period. There were no adverse events associated with multidisciplinary therapy.
Conclusion
Our findings suggest that outpatient multidisciplinary therapy has positive effects on manual dexterity and muscle strength, but no meaningful effects on mobility, balance, cardiorespiratory endurance and upper extremity muscle strength in patients with HD. Larger randomized controlled trials are needed to confirm these preliminary findings.
Objectives
Serum neurofilament light protein (NfL) is a promising marker of disease onset and progression in Huntington's disease (HD). This study investigated associations between lifestyle factors ...and NfL levels in HD mutation carriers compared to healthy age‐ and sex‐matched controls.
Materials and Methods
Participants included 29 HD mutation carriers and 15 healthy controls. Associations between serum NfL concentrations and lifestyle factors, including cardiorespiratory fitness, social network size and diversity, physical activity, cognitive reserve, smoking status, and alcohol consumption, were examined using a stepwise multivariable linear regression model.
Results
Higher NfL levels were associated with lower cognitive reserve, social network size and diversity and cardiorespiratory fitness in HD mutation carriers. Group × lifestyle factor effects were observed between lower serum NfL levels and a greater social network diversity.
Conclusion
These findings highlight a relationship between lifestyle factors and NfL levels in HD mutations carriers; however, longitudinal studies are required to confirm if these observed relationships persist over time.
Serum neurofilament light protein (NfL) is a promising marker of disease onset and progression in Huntington’s disease; however, it is not yet known how lifestyle factors may impact on NfL levels. Here, we report that lifestyle factors, particularly cognitive reserve, cardiorespiratory fitness and social network size and diversity, are significantly associated with NfL levels.
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