Journal of Huntington's disease最新文献

{"title":"Effects of computerized cognitive training on functional activity and connectivity in Huntington's disease: A pilot study.","authors":"Katharine Huynh, Nellie Georgiou-Karistianis, Amit Lampit, M Navyaan Siddiqui, Katharina Voigt, Julie C Stout, Sharna D Jamadar","doi":"10.1177/18796397251399752","DOIUrl":"10.1177/18796397251399752","url":null,"abstract":"<p><p>BackgroundComputerized cognitive training (CCT) has been found to improve cognition by altering functional activity and functional connectivity of brain networks in people with and without cognitive impairment. The effects of CCT on functional brain networks in Huntington's disease (HD) have not been comprehensively examined.ObjectiveIn our pilot trial of CCT, we aimed to explore effects of CCT on functional activity and connectivity of fronto-striatal regions during processing speed and cognitive flexibility tasks, and functional connectivity of resting-state networks in HD.MethodsSixteen participants in pre-manifest and early stages of HD were randomised to either a 12-week multi-domain CCT intervention (<i>n</i> = 6) or lifestyle education (<i>n</i> = 10). Participants completed a 1-h magnetic resonance imaging (MRI) scan at baseline and follow-up, which included task-based and resting-state functional MRI. Analyses examined changes in functional activity and connectivity of fronto-striatal regions during processing speed and cognitive flexibility task performance, as well as functional connectivity within default mode and frontoparietal resting-state networks.ResultsWhile there was evidence of benefits to in-scanner task performance, there were no significant effects on functional activity or functional connectivity of fronto-striatal regions during task performance, or resting-state functional connectivity.ConclusionCCT did not generate significant effects on functional activity or connectivity of fronto-striatal networks associated with processing speed or cognitive flexibility, or resting-state networks in HD. A larger study is required to further examine the effects of CCT on functional brain outcomes and potential moderating factors.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"124-136"},"PeriodicalIF":3.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145604467","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":"Letter in response to Fuller et al., Functional Rating Scale 2.0 (FuRST 2.0): A patient-reported outcome measure of function for Huntington's disease.","authors":"Brett L Kinsler, Chad Heatwole","doi":"10.1177/18796397251376458","DOIUrl":"10.1177/18796397251376458","url":null,"abstract":"","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"403-404"},"PeriodicalIF":3.1,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029933","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":"Mapping the landscape of caregiver burden in Huntington's Disease: Current evidence and future directions.","authors":"Katerina Poprelka, Theodoros Fasilis, Panayiotis Patrikelis, Evniki Ntinopoulou, Anastasia Verentzioti, Maria Stefanatou, Athanasia Alexoudi, Lampis C Stavrinou, Stefanos Korfias, Stylianos Gatzonis","doi":"10.1177/18796397251377237","DOIUrl":"10.1177/18796397251377237","url":null,"abstract":"<p><p>IntroductionHuntington's Disease (HD) is a rare neurodegenerative disease that profoundly affects both individuals diagnosed with the condition and their caregivers. This review aims to examine the burden experienced by informal caregivers of patients with HD and identify relevant factors that exacerbate or mitigate this burden.MethodsThe PRISMA guidelines were followed, and an extensive search of electronic databases (PubMed, Science Direct, Taylor & Francis) was undertaken to identify original research articles published in English between January 2005 and April 2025. Two reviewers independently screened the studies. The quality of the studies was evaluated using the Critical Appraisal Program (CASP). Data were extracted, and a narrative synthesis was conducted to integrate and summarize the results.ResultsTwelve studies were included in the review involving 569 caregivers of patients with HD. Studies were conducted in Europe, the United States, Canada, and Australia, with one taking place in South Korea. Patient demographics, caregiver characteristics, disease-related factors, disrupted family dynamics, caregivers' compromised mental health, and availability to access networks are related to caregiver burden. Neuropsychiatric symptoms and the hereditary nature of the disease have been identified as important correlates of caregiver strain.ConclusionCaring for individuals with HD involves a distinct and multifaceted burden shaped by both the nature of the illness and inadequate external support. Addressing this requires future research to develop tailored interventions and tools that reflect the unique needs of HD caregivers across varying stages and cultural contexts.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"304-318"},"PeriodicalIF":3.1,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145054046","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":"Dysregulation of huntingtin interacting protein networks in human juvenile Huntington's disease brain.","authors":"Sonia Podvin, Brin Rosenthal, Charles Mosier, Enlin Wei, Kathleen M Fisch, Vivian Hook","doi":"10.1177/18796397251358348","DOIUrl":"10.1177/18796397251358348","url":null,"abstract":"<p><p>BackgroundHuman Huntington's disease (HD) is a genetic neurodegenerative disorder caused by the mutant <i>HTT</i> gene containing CAG repeat expansions, resulting in motor dysfunction and behavioral deficits. CAG repeats of 40-53 occur in adult HD and 60-120 repeats occur in early onset juvenile HD, differing from the normal range of 5-35 repeats.ObjectiveThe <i>HTT</i> gene is translated to the huntingtin (HTT) protein that interacts with proteins in the development of HD. There have been few studies of HTT protein interactors in human HD brain. Therefore, this study evaluated the hypothesis that dysregulation of HTT protein interactors occurs in human juvenile HD brains.MethodsThe strategy of this study was to analyze proteomic data of human juvenile HD brain putamen and cortex regions for dysregulation of HTT interacting proteins, using a database that we compiled of HTT interactors identified in HD model systems from yeast to HD mice.ResultsResults showed significant dysregulation of HTT protein interactors of mitochondria, signal transduction, RNA splicing, chromatin organization, translation, membrane trafficking, endocytosis, vesicle, protein modification, granule membrane, and macroautophagy pathways. The majority of downregulated and upregulated HTT interactors occurred in the putamen region compared to cortex. Dysregulation displayed downregulation of mitochondria and signal transduction interactors, combined with upregulation of RNA splicing, chromatin organization, and translational interactors. Network analysis revealed interactions among clusters of HTT interactors.ConclusionsThese findings demonstrate prevalent dysregulation of HTT protein interactors in human juvenile HD brain, especially in the putamen region that controls movement deficits in HD.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"354-368"},"PeriodicalIF":3.1,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12602727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698656","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":"Reliability and validity of the Huntington's Disease Everyday Functioning (Hi-DEF): A patient-reported measure of cognitive capacity on daily functioning in Huntington's disease.","authors":"Jennifer Petrillo, Ruta Sawant, Rebecca Rogers, Sophie Cleanthous, Stefan Cano, Rajeev Kumar, Jennifer Klapper, Luis A Sierra, Jee Bang, Karen Elta Anderson, Deborah A Hall, Susan Perlman, Henry Moore, Danny Bega, Jason Johannesen, Emma Elliott","doi":"10.1177/18796397251358375","DOIUrl":"10.1177/18796397251358375","url":null,"abstract":"<p><p>BackgroundThe Huntington's Disease (HD) Everyday Functioning (Hi-DEF) is a novel patient-reported outcome (PRO) scale developed to assess the impact of cognitive impairment on daily functioning in early HD patients.ObjectiveTo examine the psychometric properties, including reliability and validity, of the Hi-DEF. Findings from psychometric analyses using classical test theory (CTT) approach are presented here.MethodsA non-interventional validation study was conducted across nine HD Centers of Excellence across the US.ResultsPatients with HD (n = 151) were recruited: 59% were female, mean (SD) age was 47 (12) years, and mean (range) Total Functional Capacity (TFC) score was 11.4 (8-13). Excellent internal consistency reliability was observed for the Hi-DEF scale total score (Cronbach's alpha: 0.98) and across subscales (alpha range 0.87-0.96). Most targeting and scaling assumptions were met, although there were ceiling effects for three subscales. Construct validity was demonstrated by moderate to high Spearman's rank-order correlations with TFC scores (range r = -0.38 to -0.62) and known and validated measures such as the HD-PRO-TRIAD^TM (range r = 0.75-0.90), and ability to discriminate between levels of functional impairment (TFC 13, 12-11, and 10-8; <i>p</i> < 0.001). Correlations with Cambridge Neuropsychological Test Automated Battery (CANTAB) cognitive performance measures were low to moderate and ranged from 0.06 to 0.38.ConclusionsThe Hi-DEF is a reliable and valid PRO scale measuring the impact of cognitive impairment on daily functioning, assessing facets of cognitive functioning in context of activities of daily living impacted in early stages of HD.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"369-381"},"PeriodicalIF":3.1,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12602719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682720","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":"Understanding the relationship between patient-reported outcome measures, clinician-rated assessments, and performance-based measures (cognitive tests and device-based estimates) of symptoms and functioning in people with Huntington's disease.","authors":"Noelle E Carlozzi, Jonathan P Troost, Wendy L Lombard, Jennifer A Miner, Praveen Dayalu","doi":"10.1177/18796397251366313","DOIUrl":"10.1177/18796397251366313","url":null,"abstract":"<p><p>BackgroundGiven the progressive cognitive decline in Huntington's disease (HD), most research in this population relies solely on objective assessments of symptoms and function, rather than on patient-reported outcome (PRO) measures.ObjectiveThe purpose of this paper is to understand how PRO measures relate to clinician-rated assessments and performance-based measures (cognitive tests and device-based estimates) of symptoms and functioning in people with HD.MethodsWe enrolled N = 52 participants with HD in this study. Participants completed several self-reported PROs as well as clinician-administered assessments and performance-based measures (cognitive tests and device-based estimates) of related concepts. Pearson correlations and linear regression models were used to examine the concordance among PROs, clinician-rated assessments, and performance-based measures.ResultsThere were strong relationships among PROs that assessed related concepts. There were also strong relationships between PROs and associated clinician-rated assessments of physical functioning (chorea, sleep/fatigue) and mental health, and slightly less robust relationships between the PROs and associated clinician-rated assessments for speech/swallowing and cognition. Relationships between PROs and associated performance-based measures were moderate for chorea/motor functioning, but negligible for sleep/fatigue and cognition.ConclusionsFindings from this study support the construct validity of PROs that assess motor functioning and mental health among individuals with HD and indicate that PROs and clinician-rated assessments of these constructs (i.e., motor functioning and mental health) provide complementary information. On the other hand, the negligible relationships between PROs and associated performance-based cognitive tests and between PROs and associated wearable device-based estimates of sleep and physical activity indicate that reliance solely on HD patients' self-report for these concepts might be misleading.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"382-395"},"PeriodicalIF":3.1,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957035","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":"Tipping the PARylation scale: Dysregulation of PAR signaling in Huntington and neurodegenerative diseases.","authors":"Christina Peng, Tamara Maiuri, Ray Truant","doi":"10.1177/18796397251372667","DOIUrl":"10.1177/18796397251372667","url":null,"abstract":"<p><p>Poly(ADP-ribosyl)ation (PARylation), a crucial post-translational modification, is catalyzed by ADP-ribosyltransferases (ARTs) and has significant implications in various cellular processes, including DNA damage response, cell signaling, and immune processes. Aberrant PAR signaling is implicated in numerous neurodegenerative diseases, including Alzheimer, Parkinson, amyotrophic lateral sclerosis, and cerebellar ataxia, where increased PAR levels and PARP1 activity are commonly observed. However, Huntington disease exhibits a unique characteristic: reduced PAR levels and impaired PARP1 activity even in prodromal phase. This finding challenges the prevailing understanding of PAR's role in neurodegeneration and suggests that dysregulation of PAR signaling, whether through overactivation or suppression, can lead to neuronal dysfunction. Herein, we discuss how this balance may impact neurodegenerative diseases, and possible connections between PAR signaling and emerging modifiers of disease onset identified by HD genome-wide association studies (GWAS).</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"293-303"},"PeriodicalIF":3.1,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12602731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144992641","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":"Reply to: In Response to Fuller et al., Functional Rating Scale 2.0 (FuRST 2.0): A patient-reported outcome measure of function for Huntington's disease.","authors":"Neha Sinha, Rebecca Lm Fuller, Glenn T Stebbins","doi":"10.1177/18796397251378980","DOIUrl":"10.1177/18796397251378980","url":null,"abstract":"","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"405-406"},"PeriodicalIF":3.1,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251433","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":"Effective housing and support models for people with Huntington's disease: A scoping review.","authors":"Lee Cubis, Elise Davis, Sharyn McDonald, Clement T Loy, Emily Gosden-Kaye, Hannah Jarman, Di Winkler, Jacinta Douglas","doi":"10.1177/18796397251378091","DOIUrl":"10.1177/18796397251378091","url":null,"abstract":"<p><p>BackgroundPeople with Huntington's disease (HD) experience physical, cognitive, and psychiatric manifestations that can result in housing in settings that are inappropriate for care requirements.ObjectiveThe aim of this scoping review was to examine the existing literature on effective housing and support models for people with HD.MethodFive major databases (MEDLINE, CINAHL, SCOPUS, PsycINFO, and EMBASE) were systematically searched for studies that reported qualitative and/or quantitative findings on housing and support models for people with HD. Key findings from eight eligible studies were integrated to provide preliminary information about housing and support for this population.ResultsNo studies included in the review specifically provided data on the effectiveness of housing and support models for people with HD. However, important insights regarding the challenges facing this population in accessing appropriate housing and supports were revealed. Findings highlighted the importance of good quality disability and health supports from adequately trained staff. People with behavioral manifestations, poor physical status and psychosocial concerns were more likely to be living in residential aged care than in their own home. The role of positive behavior support and supporting caregivers were highlighted as important considerations.ConclusionsThere is limited research on effective housing and support models for people with HD. Due to the wide variety in sociocultural variables and disease manifestations, it is unlikely that a single best-practice model exists. Housing and supports should be flexible and adapted to individual needs.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"340-353"},"PeriodicalIF":3.1,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145308331","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":"Bias in HD-ISS staging introduced by the FreeSurfer cross-sectional stream: Insights from the Huntington's Disease Young Adult Study (HD-YAS).","authors":"Harry Knights, Annabelle Coleman, Mena Farag, Michela Leocadi, Michael Murphy, Kate Fayer, Olivia Thackeray, Douglas Langbehn, Nicola Hobbs, Sarah J Tabrizi, Rachael I Scahill","doi":"10.1177/18796397251366900","DOIUrl":"10.1177/18796397251366900","url":null,"abstract":"<p><p>Huntington's Disease Integrated Staging System (HD-ISS) stages are likely inclusion criteria in future clinical trials. Stage 1 volumetric cut-offs were derived using the FreeSurfer longitudinal stream (LG). However, trials will require cross-sectional stream (CS) application with one MRI. Volumetric outputs are not robust to software type or version. T1-weighted images from 88 participants with MRIs from baseline and follow-up HD-YAS visits were segmented using both streams. CS calculated smaller caudate and putamen volumes adjusted for total intracranial volume, with greater reduction for larger volumes, shifting towards HD-ISS stage 1. CS-specific cut-offs need to be established before application to clinical trials.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"396-402"},"PeriodicalIF":3.1,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12602721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835272","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}