Journal of Huntington's disease最新文献

Background: Huntington's disease (HD) is an autosomal dominant, progressive neurodegenerative disorder debilitating mainly in adults.

Objective: This study aimed to assess the trends in HD-related mortality regarding various demographic factors.

Methods: Death certificates from the CDC WONDER were studied from 1999 to 2019, for HD-related mortality in adults aged 25 + years. Age-adjusted Mortality Rate (AAMR) per 100,000 persons and Annual Percentage Change (APC) were calculated and stratified by year, age groups, gender, race/ethnicity, state, census region, urbanization, and place of death.

Results: Between 1999 to 2019, 22,595 deaths occurred in adults due to HD. The AAMR increased from 0.43 to 0.54 during this period (APC = 0.50; 95% CI: 0.18 to 0.84). Old adults (65-85 + years) had the highest overall AAMR, followed by middle-aged adults (45-64 years) and young adults (25-44 years) (AAMR old: 1.01 vs. AAMR middle-age: 0.68 vs. AAMR young: 0.16). Men had slightly greater overall AAMRs than women (AAMR men: 0.54 vs. AAMR women: 0.48). When stratified by race, non-Hispanic (NH) Whites had significantly higher mortality rates than NH African Americans (AAMR NH White: 0.61 vs. NH African American: 0.35), while the AAMR were lowest in Hispanic/Latino (0.28). The AAMRs also showed variation by region (overall AAMR: Midwest: 0.63, Northeast: 0.47, West: 0.48, South: 0.46), and non-metropolitan areas had higher HD-related AAMR (0.66) than metropolitan areas (0.47).

Conclusions: HD-related mortality in US adults has increased since 1999. Reflecting on the variations in trends observed, new strategies are required to optimize the quality of care in long-term care facilities.

Structural magnetic resonance imaging (MRI) is a powerful tool to visualize 3D neuroanatomy and assess pathology and disease progression in neurodegenerative disorders such as Huntington's disease (HD). The development of mouse models of HD that reproduce many of the psychiatric, motor and cognitive impairments observed in human HD has improved our understanding of the disease and provided opportunities for testing novel therapies. Similar to the clinical scenario, MRI of mouse models of HD demonstrates onset and progression of brain pathology. Here, we provided an overview of the articles that used structural MRI in mouse models of HD to date, highlighting the differences between studies and models and describing gaps in the current state of knowledge and recommendations for future studies.

Background: The Huntington's Disease (HD) Everyday Functioning (Hi-DEF) is a new patient-reported outcome (PRO) instrument designed to measure the impact of cognitive impairment on daily functioning in the early stages of HD.

Objective: To assess the measurement properties and finalize item content of the Hi-DEF.

Methods: A cross-sectional, observational psychometric validation study was conducted among individuals with early stages of HD at 9 US centers of excellence. Rasch Measurement Theory (RMT) analysis of the initial draft version of the Hi-DEF (47 items) and subscales (i.e., 'Home', 'At work', 'Driving', and 'Communication') was conducted to examine measurement properties including sample-to-scale targeting, suitability of response scale (ordering of response thresholds), scale cohesiveness (item fit), local independence, and person fit.

Results: 151 participants (mean age 47 years (SD 12), 59% female) were included. Seven items were removed based on dependency and item fit. The remaining 40-item version of the Hi-DEF demonstrated good measurement properties. Across the four subscales, targeting ranged from 49-70% (72% full scale), reliability ascertained by person separation index ranged from 0.53-0.87 (0.92 full scale), response scales were ordered for 25-100% of items (75% full scale), 0-12% items displayed misfit (2% full scale), and 0-1% (2% full scale) item pairs displayed dependency.

Conclusions: Our study supports the psychometric integrity of the Hi-DEF as a reliable and valid new PRO instrument designed to assess the impact of cognitive impairment on daily functioning in the early stages of HD. Future work will evaluate the external validity and utility in clinical trial applications.

Background: Huntington's disease (HD) presents patients and individuals at risk for HD with significant levels of stress. However, relatively little research has examined how individuals cope with stress related to the disease or the association of specific coping strategies with psychological symptoms.

Objective: This study examined the ways in which HD patients and at-risk individuals cope with HD-related stress using a control-based model of coping and the association of coping strategies with symptoms of depression and anxiety.

Methods: HD patients (n = 49) and at-risk individuals (n = 76) completed the Responses to Stress Questionnaire - Huntington's Disease Version to assess coping strategies in response to HD-related stress, as well as standardized measures of depression and anxiety symptoms. Patient health records were accessed to obtain information related to disease characteristics.

Results: Patients and at-risk individuals reported using comparable levels of primary control coping, secondary control coping, and disengagement coping strategies. In linear regression analyses, only secondary control coping was significantly associated with lower depression (β= -0.62, p < 0.001) and anxiety (β= -0.59, p < 0.001) symptoms in patients and at-risk individuals (β= -0.55, p < 0.001 and β= -0.50, p < 0.001, respectively).

Conclusions: Secondary control coping may be beneficial for both HD patients and at-risk individuals. Future research using the control-based model of coping in longitudinal studies with the HD population is needed, and future interventions could test the effects of cognitive reframing and acceptance as coping strategies for families affected by HD.

Background: Huntington's disease (HD) exerts significant impacts on individuals and families worldwide. Nevertheless, data on its economic burden in Brazil are scarce, revealing a critical gap in understanding the associated healthcare costs.

Objective: This study was conducted at a tertiary neurology outpatient clinic in Brazil with the aim of assessing annual healthcare service utilization and associated costs for HD patients.

Methods: We conducted a cross-sectional observational study involving 34 HD patients. A structured questionnaire was applied to collect data on direct medical costs (outpatient services, medications), non-medical direct costs (complementary therapies, mobility aids, home adaptations), and indirect costs (lost productivity, caregiver costs, government benefits) over one year.

Results: Significant economic impacts were observed, with average annual direct medical costs of $4686.82 per HD patient. Non-medical direct and indirect costs increased the financial burden, highlighting extensive resource utilization beyond healthcare services. Thirty-three out of 34 HD patients were unemployed or retired, and 16 relied on government benefits, reflecting broader socioeconomic implications. Despite the dataset's limitations, it provides crucial insights into the economic impact of HD on patients and the Brazilian public health system.

Conclusions: The findings underscore the urgent need for a more comprehensive evaluation of the costs to inform governmental policies related to HD. Future research is needed to expand the data pool and develop a nuanced understanding of the economic burdens of HD to help formulate effective healthcare strategies for patients.

Background: Juvenile-onset Huntington's disease (JHD) represents 1-5% of Huntington's disease (HD) patients, with onset before the age of 21. Pediatric HD (PHD) relates to a proportion of JHD patients that is still under 18 years of age. So far, both populations have been excluded from interventional trials.

Objective: Describe the prevalence and incidence of JHD and PHD in the Netherlands and explore their ability to participate in interventional trials.

Methods: The prevalence and incidence of PHD and JHD patients in the Netherlands were analyzed. In addition, we explored proportions of JHD patients diagnosed at pediatric versus adult age, their diagnostic delay, and functional and modelled (CAP100) disease stage in JHD and adult-onset HD patients at diagnosis.

Results: The prevalence of JHD and PHD relative to the total manifest HD population in January 2024 was between 0.84-1.25% and 0.09-0.14% respectively. The mean incidence of JHD patients being diagnosed was between 0.85-1.28 per 1000 patient years and of PHD 0.14 per 1.000.000 under-aged person years. 55% of JHD cases received a clinical diagnosis on adult age. At diagnosis, the majority of JHD patients was functionally compromised and adolescent-onset JHD patients were significantly less independent compared to adult-onset HD patients.

Conclusions: In the Netherlands, the epidemiology of JHD and PHD is lower than previously suggested. More than half of JHD cases are not eligible for trials in the PHD population. Furthermore, higher functional dependency in JHD patients influences their ability to participate in trials. Lastly, certain UHDRS functional assessments and the CAP100 score do not seem appropriate for this particular group.

Background: Clinical guidelines recommend that people with Huntington's disease (HD) should exercise to maintain/improve fitness and motor function, yet physical activity levels remain low in this group. Promotion of physical activity is often via care partners with little evidence that they are supported in this role.

Objective: The aim was to co-design a resource for care partners of people with HD to support promotion of physical activity.

Methods: A four-step co-design approach was used to develop a care partner resource. Five care partners took part in an online workshop exploring experiences and the knowledge, support and skills needed by care partners to promote physical activity. A co-design team (n = 7) developed a prototype that was user tested by three people who had attended the workshop. Findings from user testing were used to develop the final resource.

Results: An easy to read, image-based prototype was developed that contained tips on planning activity, safety and activity examples. User testing identified the need for grouping of activities suitable for 10, 20, and 30 minutes of available time, information on maintaining and improving activity and re-organization of information to support engagement of activity.

Conclusions: A resource for care partners that has been translated into seven languages was developed to promote physical activity. User testing indicated confidence in using the resource and appreciation of the autonomy provided to the person with HD to plan activities. Further work is needed to evaluate the impact of the resource in promotion of physical activity and the impact on care partner burden.

 Huntington's disease (HD) is a devastating neurodegenerative disorder characterized by impaired motor function and cognitive decline, ultimately leading to death. HD is caused by a polyglutamine expansion in the N-terminal region of the huntingtin (HTT) protein, which is linked to decreased HTT turnover, increased HTT proteolysis, increased HTT aggregation, and subsequent neuronal death. In this review, we explore the mechanism of the protective effect of blocking HTT proteolysis at D586, which has been shown to rescue the HD phenotype in HD mouse models. Until recently, the mechanism remained unclear. Herein, we discuss how blocking HTT proteolysis at D586 promotes HTT turnover by correcting autophagy, and making HTT a better autophagy substrate, through post-translational myristoylation of HTT at G553.

Speech alterations have been reported in manifest Huntington's disease (HD) and premanifest mutation carriers (preHD). The aim of our study was to explore these alterations in preHD and whether they can be used as biomarkers. 13 preHD mutation carriers performed reading task, sustained phonation task and syllable repetition tasks at baseline and after 21 months, as well as clinical examination and MRI. Syllable repetition capacity and self-chosen velocity of single syllable repetition differed significantly between time points. There were no changes in clinical ratings or MRI volumetry. Measurements of speech might be sensitive tools for monitoring subclinical changes in preHD.

Background: For various genetic disorders characterized by expanded cytosine-adenine-guanine (CAG) repeats, such as spinocerebellar ataxia (SCA) subtypes and Huntington's disease (HD), genetic interventions are currently being tested in different clinical trial phases. The patient's perspective on such interventions should be included in the further development and implementation of these new treatments.

Objective: To obtain insight into the thoughts and perspectives of individuals with SCA and HD on genetic interventions.

Methods: In this qualitative study, participants were interviewed using semi-structured interview techniques. Topics discussed were possible risks and benefits, and logistic factors such as timing, location and expertise. Data were analyzed using a generic thematic analysis. Responses were coded into superordinate themes.

Results: Ten participants (five with SCA and five with HD) were interviewed. In general, participants seemed to be willing to undergo genetic interventions. Important motives were the lack of alternative disease-modifying treatment options, the hope for slowing down disease progression, and preservation of current quality of life. Before undergoing genetic interventions, participants wished to be further informed. Logistic factors such as mode and frequency of administration, expertise of the healthcare provider, and timing of treatment are of influence in the decision-making process.

Conclusions: This study identified assumptions, motives, and topics that require further attention before these new therapies, if proven effective, can be implemented in clinical practice. The results may help in the design of care pathways for genetic interventions for these and other rare genetic movement disorders.