Journal of Huntington's disease最新文献

{"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":"https://doi.org/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":"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":"https://doi.org/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":"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":"https://doi.org/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":"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":"https://doi.org/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":"https://doi.org/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}

{"title":"Upcoming meetings related to Huntington's disease.","authors":"","doi":"10.1177/18796397241306778","DOIUrl":"https://doi.org/10.1177/18796397241306778","url":null,"abstract":"","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":"13 4","pages":"569"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458278","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":"What Huntington's Disease Patients Say About Their Illness: An Online Direct-to-Participant Pilot Study.","authors":"Karen E Anderson, Lakshmi Arbatti, Abhishek Hosamath, Andrew Feigin, Jody Goldstein, Elise Kayson, Brett L Kinsler, Lauren Falanga, Lynn Denise, Noelle E Carlozzi, Samuel Frank, Katie Jackson, Sandra Kostyk, Jennifer L Purks, Kenneth P Serbin, Shari Kinel, Christopher A Beck, Ira Shoulson","doi":"10.3233/JHD-231520","DOIUrl":"10.3233/JHD-231520","url":null,"abstract":"<p><strong>Background: </strong>Direct-to-participant online reporting facilitates the conduct of clinical research by increasing access and clinically meaningful patient engagement.</p><p><strong>Objective: </strong>We assessed feasibility of online data collection from adults with diagnosed Huntington's disease (HD) who directly reported their problems and impact in their own words.</p><p><strong>Methods: </strong>Data were collected online from consenting United States residents who self-identified as 1) having been diagnosed with Huntington's disease, 2) able to ambulate independently, and 3) self-sufficient for most daily needs. Data for this pilot study were collected using the Huntington Study Group myHDstory online research platform. The Huntington Disease Patient Report of Problems (HD-PROP), an open-ended questionnaire, was used to capture verbatim bothersome problems and functional impact. Natural language processing, human-in-the-loop curation of verbatim reports involving clinical and experience experts, and machine learning classified verbatim-reports into clinically meaningful symptoms.</p><p><strong>Results: </strong>All 8 questionnaires in the online pilot study were completed by 345 participants who were 60.9% men, 34.5±9.9 (mean±SD) years old, and 9.5±8.4 years since HD diagnosis. Racial self-identification was 46.4% Caucasian, 28.7% African American, 15.4% American Indian/Alaska Native, and 9.5% other. Accuracy of verbatim classification was 99%. Non-motor problems were the most frequently reported symptoms; depression and cognitive impairment were the most common.</p><p><strong>Conclusions: </strong>Online research participation was feasible for a diverse cohort of adults who self-reported an HD diagnosis and predominantly non-motor symptoms related to mood and cognition. Online research tools can help inform what bothers HD patients, identify clinically meaningful outcomes, and facilitate participation by diverse and under-represented populations.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"237-248"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140857282","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":"Gut Microbiota as a Modifier of Huntington's Disease Pathogenesis.","authors":"Ali Khoshnan","doi":"10.3233/JHD-240012","DOIUrl":"10.3233/JHD-240012","url":null,"abstract":"<p><p>Huntingtin (HTT) protein is expressed in most cell lineages, and the toxicity of mutant HTT in multiple organs may contribute to the neurological and psychiatric symptoms observed in Huntington's disease (HD). The proteostasis and neurotoxicity of mutant HTT are influenced by the intracellular milieu and responses to environmental signals. Recent research has highlighted a prominent role of gut microbiota in brain and immune system development, aging, and the progression of neurological disorders. Several studies suggest that mutant HTT might disrupt the homeostasis of gut microbiota (known as dysbiosis) and impact the pathogenesis of HD. Dysbiosis has been observed in HD patients, and in animal models of the disease it coincides with mutant HTT aggregation, abnormal behaviors, and reduced lifespan. This review article aims to highlight the potential toxicity of mutant HTT in organs and pathways within the microbiota-gut-immune-central nervous system (CNS) axis. Understanding the functions of Wild-Type (WT) HTT and the toxicity of mutant HTT in these organs and the associated networks may elucidate novel pathogenic pathways, identify biomarkers and peripheral therapeutic targets for HD.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"133-147"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11307070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140904492","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":"Towards Standardizing Nomenclature in Huntington's Disease Research.","authors":"Marian DiFiglia, Blair R Leavitt, Douglas Macdonald, Leslie M Thompson","doi":"10.3233/JHD-240044","DOIUrl":"10.3233/JHD-240044","url":null,"abstract":"<p><p>The field of Huntington's disease research covers many different scientific disciplines, from molecular biology all the way through to clinical practice, and as our understanding of the disease has progressed over the decades, a great deal of different terminology has accrued. The field is also renowned for its collaborative spirit and use of standardized reagents, assays, datasets, models, and clinical measures, so the use of standardized terms is especially important. We have set out to determine, through a consensus exercise involving basic and clinical scientists working in the field, the most appropriate language to use across disciplines. Nominally, this article will serve as the style guide for the Journal of Huntington's Disease (JHD), the only journal devoted exclusively to HD, and we lay out the preferred and standardized terminology and nomenclature for use in JHD publications. However, we hope that this article will also serve as a useful resource to the HD research community at large and that these recommended naming conventions will be adopted widely.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":"13 2","pages":"119-131"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11307060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141537925","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":"Genetic Interventions for Spinocerebellar Ataxia and Huntington's Disease: A Qualitative Study of the Patient Perspective.","authors":"Nienke J H van Os, Mayke Oosterloo, Brigitte A B Essers, Janneke P C Grutters, Bart P C van de Warrenburg","doi":"10.3233/JHD-240026","DOIUrl":"10.3233/JHD-240026","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>To obtain insight into the thoughts and perspectives of individuals with SCA and HD on genetic interventions.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"321-328"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11492111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141537923","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}