Journal of Huntington's disease最新文献

{"title":"Exploring relationships among gait, balance, and physical activity in individuals with Huntington's disease.","authors":"Lauren E Tueth, Allison M Haussler, Sidney T Baudendistel, Gammon M Earhart","doi":"10.1177/18796397241285000","DOIUrl":"10.1177/18796397241285000","url":null,"abstract":"<p><strong>Background: </strong>Individuals with Huntington's disease (HD) experience a variety of motor and non-motor symptoms, but little is known about how these symptoms are related to one another. It is important to characterize the deficits present and explore the relationships among these symptoms in order to provide high quality clinical care.</p><p><strong>Objective: </strong>The purpose of this study was to characterize gait, balance, and physical activity level in individuals with HD and explore the relationships among motor and non-motor symptoms.</p><p><strong>Methods: </strong>Individuals completed one lab visit and wore a sensor for seven days to capture physical activity level. During the lab visit, gait, balance, and cognitive status were assessed using validated measures. A 2 × 2 ANOVA (Group×Condition) was used to assess differences in gait between individuals with HD vs. controls, while t-tests were used for other clinical measures. Correlations as well as a mixed effects model explored relationships among clinical measures in the HD group.</p><p><strong>Results: </strong>Individuals with HD walk significantly slower and have significantly worse balance than controls. Gait velocity and balance were significantly correlated with cognitive status in individuals with HD. Additionally, balance performance and balance confidence were not significantly correlated, indicating that there may be a lack of self-awareness of deficits present in individuals with HD. In-lab measures were not significant predictors of physical activity.</p><p><strong>Conclusions: </strong>Motor impairments in individuals with HD are correlated with cognitive impairment. Clinicians should be aware of the impact of cognitive impairment when selecting interventions to address motor symptoms in individuals with HD.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":"13 4","pages":"557-568"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12012825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mortality trends and disparities in adults with Huntington's disease in the United States.","authors":"Humza Saeed, Abdullah, Hira Hameed, Hafiz Mohammad Maaz, Abdul Wasay, Zubair Amin, Muhammad Khubaib Arshad, Hritvik Jain, Aman Goyal","doi":"10.1177/18796397241287399","DOIUrl":"10.1177/18796397241287399","url":null,"abstract":"<p><strong>Background: </strong>Huntington's disease (HD), an autosomal dominant disorder, is characterized by progressive neurodegeneration, psychiatric issues, dementia, and worsening chorea over time. Its prevalence varies by ethnicity and region.</p><p><strong>Objective: </strong>This study aims to analyze mortality trends and disparities in adults with HD in the United States (US).</p><p><strong>Methods: </strong>This study analyzed death certificates from 1999 to 2020 for deaths due to HD (ICD-10 code G10) in individuals aged 25 and older. Age-adjusted mortality rates (AAMRs) and annual percent change (APC) were calculated by year, gender, age groups, race/ethnicity, geographics and urbanization status.</p><p><strong>Results: </strong>Between 1999 and 2020, there were 24,121 reported deaths among patients with HD. During this period, the AAMR increased from 4.3 to 6.0 per 1,000,000 population, with a notable surge from 2018 to 2020 (APC: 9.88; 95% CI: 5.45 to 13.20). Older adults exhibited the highest AAMRs at 10.4 per 1,000,000 when analyzed by age-group. Men and women had comparable AAMRs (5.2 vs. 5.0). By race, non-Hispanic (NH) Whites had the highest AAMRs (6.0), followed by NH African Americans (3.3) and Hispanics (2.8). Additionally, non-metropolitan areas experienced higher AAMRs compared to metropolitan areas (6.6 vs. 4.8).</p><p><strong>Conclusions: </strong>Since 1999, mortality from HD has increased, particularly from 2018 to 2020, with higher rates in older adults, men, NH Whites, and non-metropolitan areas. Further research is essential to consolidate data, standardize reporting practices, and address disparities to improve outcomes.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":"13 4","pages":"491-500"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study protocol for the iMarkHD study in individuals with Huntington's disease.","authors":"Daniel J van Wamelen, Naomi H Martin, Orsolya Makos, James Badenoch, Jose Manuel Valera-Bermejo, Monika Hartmann, Alay Rangel Cristales, Tobias C Wood, Mattia Veronese, Manuela Moretto, Fernando Zelaya, Flavio dell'Acqua, Owen O'Daly, David J Lythgoe, Cedric Ginestet, Federico Turkheimer, Nikki Palasits, Ladislav Mrzljak, John H Warner, Eugenii A Rabiner, Roger Gunn, Sarah J Tabrizi, Cristina Sampaio, Andrew Wood, Steven Cr Williams","doi":"10.1177/18796397241288165","DOIUrl":"10.1177/18796397241288165","url":null,"abstract":"<p><p><b>Background:</b> Huntington's disease (HD) is still often defined by the onset of motor symptoms, inversely associated with the size of the CAG repeat expansion in the <i>huntingtin</i> gene. Although the cause of HD is known, much remains unknown about mechanisms underlying clinical symptom development, disease progression, and specific clinical subtypes/endophenotypes. <b>Objective:</b> In the iMarkHD study, we aim to investigate four discrete molecular positron emission tomography (PET) tracers and magnetic resonance imaging (MRI) markers as biomarkers for disease and symptom progression. <b>Methods:</b> Following MRI optimization in five healthy volunteers (cohort 1), we aim to recruit 108 participants of whom 72 are people with HD (PwHD) and 36 healthy volunteers (cohort 2). Pending interim analysis, these numbers could increase to 96 PwHD and 48 healthy controls. Participants will complete a total of 10 study visits, consisting of a screening visit followed by a clinical and MRI visit and PET visits at baseline, year 1, and year 2. PET targets include the cannabinoid 1, histamine 3, and serotonin 2A receptors, and phosphodiesterase 10A, whereas MRI will be multimodal, including, but not limited to, the assessment of cerebral blood flow, functional connectivity, and brain iron. <b>Results:</b> Recruitment is currently active and started in September 2022. <b>Conclusions:</b> By combining PET and multi-modal MRI assessments we expect to provide a comprehensive examination of the molecular, functional, and structural framework of HD progression. As such, the iMarkHD study will provide a solid base for the identification of treatment targets and novel outcome measures for future clinical trials.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":"13 4","pages":"479-489"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Huntington's Disease Clinical Trials Update: September 2024.","authors":"Mena Farag, Sarah J Tabrizi, Edward J Wild","doi":"10.1177/18796397241293955","DOIUrl":"10.1177/18796397241293955","url":null,"abstract":"<p><p>In this edition of the Huntington's Disease Clinical Trials Update, we expand on the ongoing extension study of PTC518 from PTC Therapeutics, including 12-month interim results from the parent study. We also discuss 24-month interim results from uniQure's AMT-130 program and 28-week follow-up results from Wave Life Sciences' SELECT-HD clinical trial of WVE-003. Additionally, we provide a comprehensive listing of all currently registered and ongoing clinical trials in Huntington's disease.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":"13 4","pages":"409-418"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quality of care through the eyes of residents with Huntington's disease living in a nursing home: A qualitative explorative study.","authors":"Joyce Cf Heffels, Mayke Oosterloo, Bram de Boer, Raymund Ac Roos, Jos Mga Schols, Irma Hj Everink","doi":"10.1177/18796397241289374","DOIUrl":"10.1177/18796397241289374","url":null,"abstract":"<p><p><b>Background:</b> Moving to a nursing home is often unavoidable for late-stage patients with Huntington's disease (HD). Specialized care is needed, adjusted to the specific needs and characteristics of this usually young group within the nursing home. Despite this, there are no specific, validated methods for assessing the experienced quality of care (QoC) by HD nursing home residents. <b>Objective:</b> We used a qualitative, phenomenological approach to gain insight into the perspectives of HD residents and identify elements for assessing QoC in HD specialized nursing homes. <b>Methods:</b> Fifteen advanced-stage HD residents (Total Functional Capacity Scale 3-5), from three specialized HD nursing homes in the Netherlands, participated in semi-structured interviews from November 2022 to February 2023. Interviews were transcribed verbatim and analyzed using reflexive thematic analysis. <b>Results:</b> Residents emphasize the significance of care and daily living experiences, including meal satisfaction, support in daily activities, and a structured routine. Autonomy, well-being, and a positive living environment contribute to a sense of home. QoC is influenced by residents' ability to express preferences, choose consciously for a specialized nursing home, and caregivers' HD knowledge and competences. Positive QoC involves open, respectful conversations, family contact, and addressing topics like advance care planning. Interactions with fellow residents, including behavioural and communication challenges, also affect QoC. <b>Conclusions:</b> The experiences of nursing home residents with HD related to the QoC they receive are shaped by satisfaction with daily activities, autonomy, caregiver expertise, and fellow resident interaction. These factors are crucial for assessing QoC from the residents' perspective.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":"13 4","pages":"523-533"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Social cognition profile in early Huntington disease: Insight from neuropsychological assessment and structural neuroimaging.","authors":"Marie Caillaud, Mickael Laisney, Alexandre Bejanin, Harmony Duclos, Clarisse Scherer-Gagou, Adriana Prundean, Dominique Bonneau, Francis Eustache, Christophe Verny, Béatrice Desgranges, Philippe Allain","doi":"10.1177/18796397241291730","DOIUrl":"10.1177/18796397241291730","url":null,"abstract":"<p><strong>Background: </strong>Huntington's disease (HD) is traditionally associated with motor, cognitive, and neuropsychiatric symptoms. Recent observations suggest that disturbances in social cognition may feature prominently in HD, potentially contributing to behavioral challenges.</p><p><strong>Objective: </strong>This study aims to explore the onset and neural mechanisms underlying social cognition disturbances in HD, which are not yet well understood despite increasing recognition of these symptoms.</p><p><strong>Methods: </strong>This study compared 20 individuals in the early stages of HD with 20 healthy controls across a range of cognitive tests, in-depth social cognition assessments, and structural MRI evaluations.</p><p><strong>Results: </strong>The findings revealed alterations in various aspects of social cognition, particularly cognitive and affective Theory of Mind, in the early HD group. Some of these alterations correlated with the neurodegeneration of the striatum (caudate), suggesting that social cognition deficits may serve as early indicators of disease progression.</p><p><strong>Conclusions: </strong>This research underscores the importance of integrating social cognition evaluations into the clinical assessment of HD and hints at a complex interplay between these deficits and the broader neuropsychological impact of the disease. The results thus advocate for a more holistic approach to understanding and managing HD, considering the potential interdependencies between social cognition and other cognitive functions.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":"13 4","pages":"467-477"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cognitive impairment in Huntington's disease and its impact on functioning: Concept elicitation and cognitive debriefing for the Huntington's Disease Everyday Functioning (Hi-DEF) scale.","authors":"Jennifer Petrillo, A Alex Levine, Jason Johannesen, Teya Lovell, Alissa Rams, Stefan Cano, Karen Anderson, Jennifer Klapper, Aaron Koenig","doi":"10.1177/18796397241289044","DOIUrl":"10.1177/18796397241289044","url":null,"abstract":"<p><strong>Background: </strong>Cognitive impairment in Huntington's disease (HD) is a key driver of disability that can have deleterious impacts on everyday functioning. Currently available patient-reported outcome measures may not adequately capture the impact of HD-related cognitive impairment on daily life, particularly higher-order executive functioning (i.e., processing information, decision making, multi-tasking, planning, etc.).</p><p><strong>Objective: </strong>To address the unmet need to better quantify the functional sequelae of HD-related cognitive impairment by developing the Huntington's Disease Everyday Functioning (Hi-DEF) scale.</p><p><strong>Methods: </strong>Qualitative interviews were conducted in two adult cohorts (25-65 years) with early stages of HD (i.e., huntingtin [<i>mHTT</i>] gene carriers with self-reported cognitive complaints but could still function independently). Cohort 1 included 10 dyads of participants with HD and their care partners, who completed concept elicitation interviews to identify cognitive challenges impacting everyday tasks, which was used to design a draft item-set. Cohort 2, which included 15 additional participants with HD, cognitively debriefed this item-set.</p><p><strong>Results: </strong>In Cohort 1, issues with executive functioning were reported 32 times by participants with HD and 22 times by care partners, and challenges with functioning were reported 46 times by participants with HD and 20 times by care partners. Based on these reports, the Hi-DEF scale was developed and cognitive debriefing interviews evaluated its content validity, relevance, clarity, interpretation, and acceptability. Psychometric validation of the Hi-DEF scale is reported elsewhere.</p><p><strong>Conclusions: </strong>These interviews revealed the impact of HD-related cognitive impairment on everyday functioning and supported the content validity, relevance, clarity, interpretation, and acceptability of the Hi-DEF scale.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":"13 4","pages":"511-522"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anxiety, memory, and social impairments in the YAC128 mouse model of Huntington's disease.","authors":"Ksenia S Marinina, Ilya B Bezprozvanny, Polina A Egorova","doi":"10.1177/18796397241295668","DOIUrl":"10.1177/18796397241295668","url":null,"abstract":"<p><strong>Background: </strong>Huntington's disease (HD) is an autosomal dominant hereditary disorder, caused by an expansion of polyglutamine in the huntingtin protein. HD is characterized by a progressive decline in motor functions. This decline includes involuntary movements (chorea) and the worsening of controlled motions caused mainly by neuronal dysfunction in the striatum. In addition to the deterioration of motor symptoms, HD patients also suffer from cognitive changes, mood swings, apathy, depression, outbursts of anger, psychosis, and social withdrawal.</p><p><strong>Objective: </strong>A comprehensive examination of cognitive, affective, and social changes in the HD mouse model is required for the development of combined therapy for both motor and non-motor deficits in HD.</p><p><strong>Methods: </strong>The behavioral tests for anxiety, memory, and social traits were used in this study.</p><p><strong>Results: </strong>YAC128 HD transgenic mice exhibited anxiolytic behavior in the novel brightly illuminated environment of the open field and light-dark place preference tests. Moreover, YAC128 HD mice also suffered from a decline in their recognition memory during the novel object recognition test. YAC128 HD mice demonstrated reduced exploration interest during the open field with a non-social target as well as during the first day of the three-chamber social test. Social interaction was also impaired in YAC128 HD mice as it was shown in the social interaction with resident intruder test.</p><p><strong>Conclusions: </strong>YAC128 HD mouse model may be used as a model system to test the possible treatments for both motor and non-motor symptoms including memory loss, agitation and social withdrawal.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":"13 4","pages":"431-448"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revisiting huntingtin activity and localization signals in the context of protein structure.","authors":"Ray Truant, Rachel J Harding, Kaitlyn Neuman, Tamara Maiuri","doi":"10.1177/18796397241295303","DOIUrl":"10.1177/18796397241295303","url":null,"abstract":"<p><p>Protein localization signals and activity motifs have been defined within huntingtin since 2003. Advances in technology in protein structure determination by cryo-electron microscopy (EM) have led to 2.6 Å resolution structures of huntingtin and HAP40 for the majority of the protein, although structure of the amino terminus with the polyglutamine expansion remains elusive in the context of full-length huntingtin. Recent advances in protein modeling using neural network algorithms trained on a database of known protein structures has resulted in structure predictions that are useful for researchers but need experimental validation. Here, we use both structures solved by cryo-EM as well as modeling centered around experimental structural data to retrospectively revisit huntingtin protein localization signals identified prior to the cryo-EM and AI-enabled structural revolutions. We interrogate these models as well as put forward testable hypotheses of allosteric changes in huntingtin and how they could be affected by polyglutamine expansion. We also extended this methodology to another polyglutamine disease protein, ataxin-1, expanded in Spinocerebellar Ataxia Type 1 (SCA1).</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":"13 4","pages":"419-430"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Huntington's disease at work: The effect of profession-specific requirements as related to clinical characteristics on work outcome.","authors":"Kasper F van der Zwaan, Milou Jacobs, Raymund A C Roos, Susanne T de Bot","doi":"10.1177/18796397241288161","DOIUrl":"10.1177/18796397241288161","url":null,"abstract":"<p><strong>Background: </strong>In most Huntington's disease expanded gene carriers (HDEGC), losing work capacity is the first sign of functional decline. Cognitive deterioration, motor dysfunction, and psychiatric disturbances are associated with or predict work outcomes in HD. The role of profession-specific requirements, however, has not been investigated.</p><p><strong>Objective: </strong>This study examines the relationship between work outcomes, clinical characteristics, burnout, and profession-specific requirements in HDEGC. We hypothesize that burnout-like symptoms are associated with mild apathy and that profession-specific requirements influence clinical characteristics affecting work capacity in HD.</p><p><strong>Methods: </strong>A cohort of 117 HDEGC (CAG repeat ≥36) participated in the \"HD-work\" study at Leiden University Medical Center. Participants were 18-67 years old, either, worked at baseline, or had lost their job within two years. The Unified Huntington's Disease Rating Scale assessed motor abilities, global functioning, and cognition. The HD-work questionnaire and the 'Utrecht Burn Out Scale' assessed work problems and burnout. Statistical methods included descriptive statistics, Pearson correlations, Cronbachs alpha, t-tests, and logistic regressions.</p><p><strong>Results: </strong>Burnout-like symptoms did not differ between those with full and reduced working capacity and were not more prevalent in HD than in the general Dutch population. No significant effect was found between work outcomes and profession-specific requirements, even when adjusted for clinical characteristics.</p><p><strong>Conclusions: </strong>Our study suggests that profession-specific requirements do not significantly impact work ability among individuals with HD in early phases of HD. Workplace adjustments should be tailored to individual preferences rather than profession-specific demands. Burnout-like symptoms did not affect work capacity or relate to apathy.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":"13 4","pages":"547-555"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}