Journal of Huntington's disease最新文献

{"title":"Upcoming meetings related to Huntington's disease.","authors":"","doi":"10.1177/18796397251323357","DOIUrl":"10.1177/18796397251323357","url":null,"abstract":"","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"109"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515567","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":"Antidopaminergic medications in Huntington's disease.","authors":"Andrew M Tan, Michal Geva, Y Paul Goldberg, Henk Schuring, Bernd-Jan Sanson, Anne Rosser, Lynn Raymond, Ralf Reilmann, Michael R Hayden, Karen Anderson","doi":"10.1177/18796397241304312","DOIUrl":"10.1177/18796397241304312","url":null,"abstract":"<p><p>Huntington's disease (HD) is a progressive neurodegenerative disorder marked by motor, cognitive, and behavioral impairments. Antidopaminergic medications (ADMs), such as VMAT2 inhibitors and antipsychotics, are commonly used to manage HD motor disturbances and behavioral disorders. For patients and caregivers, ADMs are an important tool for managing symptoms that negatively affect daily life. However, the impact of ADM use in HD is not firmly understood due to a lack of robust, systematic studies that assessed their overall effect on HD disease. A mounting body of evidence suggests these medications may be associated with worse clinical measures of cognitive function and functional impairment. While regulatory guidelines highlight adverse effects like sedation, cognitive dysfunction, and extrapyramidal symptoms, it is unclear whether ADMs directly impact disease progression or if the side effects mimic or exacerbate measures of HD symptoms in clinical trials. Given ADM effects on the central nervous system and biological uncertainty within HD outcomes, clinical trial designs should recognize the impact of ADMs on key outcomes, as measured by acceptable scales including Total Functional Capacity, Stoop Word Reading, Symbol Digit Modality Test, and the composite Unified Huntington's Disease Rating Scale. The development of novel HD interventions requires consideration of concomitant ADM use that may influence measures of disease presentation. In this review, we highlight the role of ADMs in HD management, their symptomatic benefits and potential risks, especially with high dose associated side effects, interactions with CYP2D6 inhibitors, and the individualized need for careful dose monitoring for clinical care and trial design.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"16-29"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458285","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":"Frequency of depression in Huntington's disease: A systematic review and meta-analysis.","authors":"Shayan Abdollah Zadegan, Frank Ramirez, Jung Woo Park, Natalia Pessoa Rocha, Erin Furr Stimming, Antonio L Teixeira","doi":"10.1177/18796397241301774","DOIUrl":"10.1177/18796397241301774","url":null,"abstract":"<p><p>BackgroundHuntington's disease (HD) is a hereditary neurodegenerative disease characterized by a combination of motor, cognitive, and mental health issues, with depression being the most common. Despite its importance, the relationship between depression and disease progression is still debatable.ObjectiveThe primary objective of this study was to examine the frequency of depression across different disease stages in individuals with HD. We also explored the associations between depression and other HD-related factors.MethodsThis systematic review comprehensively searched MEDLINE, APA PsycINFO, and Embase databases for studies on depression in individuals with HD. Pooled depression frequencies were calculated for premanifest and manifest HD. Depression was analyzed based on HD functional stages and diagnostic tools, alongside reviewing its association with various HD factors.ResultsWe assessed 6523 records and included 104 studies. Our meta-analyses revealed that the overall frequency of depression was higher in manifest HD compared to premanifest HD (0.38 vs. 0.23). However, the progression of depression did not follow a consistent pattern, with peaks occurring in earlier rather than later stages. Additionally, the frequency of depression was lower in studies using diagnostic criteria compared to those using clinical scales (0.25 vs. 0.42).ConclusionsOur findings showed that the rate of depression is high in HD and varies depending on the disease stage and the criteria used. This emphasizes the necessity for tailored and unified diagnostic criteria for depression in HD.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"43-58"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458213","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":"Absence of hippocampal pathology persists in the Q175DN mouse model of Huntington's disease despite elevated HTT aggregation.","authors":"Melissa A Solem, Ross G Pelzel, Nicholas B Rozema, Taylor G Brown, Emma Reid, Rachel H Mansky, Rocio Gomez-Pastor","doi":"10.1177/18796397251316762","DOIUrl":"10.1177/18796397251316762","url":null,"abstract":"<p><p>BackgroundHuntington's disease (HD) is a neurodegenerative disorder causing motor, cognitive, and psychiatric impairments, with the striatum being the most affected brain region. However, the role of other regions, such as the hippocampus, in HD remains less understood.ObjectiveHere, we study the comparative impact of enhanced mHTT aggregation and neuropathology in the striatum and hippocampus of two HD mouse models.MethodsWe utilized the zQ175 as a control HD mouse model and the Q175DN mice lacking the PGK-Neomycin cassette generated in house. We performed a comparative characterization of the neuropathology between zQ175 and Q175DN mice in the striatum and the hippocampus by assessing HTT aggregation, neuronal and glial pathology, chaperone expression, and synaptic density.ResultsWe showed that Q175DN mice presented enhanced mHTT aggregation in both striatum and hippocampus compared to zQ175. Striatal neurons showed a greater susceptibility to enhanced accumulation of mHTT in Q175DN. On the contrary, no signs of hippocampal pathology were found in zQ175 and absence of hippocampal pathology persisted in Q175DN mice despite higher levels of mHTT. In addition, Q175DN hippocampus presented increased synaptic density, decreased Iba1⁺ microglia density and enhanced HSF1 levels in specific subregions of the hippocampus compared to zQ175.ConclusionsQ175DN mice are a valuable tool to understand the fundamental susceptibility differences to mHTT toxicity between striatal neurons and other neuronal subtypes. Furthermore, our findings also suggest that cognitive deficits observed in HD animals might arise from either striatum dysfunction or other regions involved in cognitive processes but not from hippocampal degeneration.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"59-84"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458293","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":"Acceptance and commitment therapy with Huntington's disease: A narrative review and case report of a caregiver-assisted intervention.","authors":"Simone H Schriger, Chelsi N Nurse, C Virginia O'Hayer","doi":"10.1177/18796397251315162","DOIUrl":"10.1177/18796397251315162","url":null,"abstract":"<p><p>Acceptance and commitment therapy (ACT) is an experiential, action-oriented talk therapy that emphasizes acceptance of painful inner experience through increased psychological flexibility. In this narrative review and case report, we first review the extant literature on applications of ACT to patients with a variety of mental and physical health challenges, including neurodegenerative disorders, and their caregivers. We then discuss applications of ACT to Huntington's disease (HD). We provide a case report of a 52-year-old man living with HD who, accompanied by his caregiver, received a virtually-delivered 6-session ACT intervention. We measured the patient's self-reported symptoms of depression (PHQ-9) and anxiety (GAD-7) as well as his health-related quality of life (HDQoL) and level of cognitive fusion (i.e., being attached to his thoughts; CFQ-13) at baseline and following the intervention. At follow-up, the patient had a clinically significant reduction in depressive symptoms (from moderate to mild symptomatology) and cognitive fusion. Further, the patient had improvements in quality of life across the domains of physical functioning, mood, and worries. The promising outcomes of this case, as well as extant literature on the effectiveness of ACT in supporting individuals with similar neurodegenerative disorders, suggests that ACT may hold promise as a scalable and impactful intervention for individuals living with HD and their caregivers. We conclude with a call for further study of ACT with this population to build a more robust evidence base that can be used to benefit individuals living with HD and their caregivers.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"3-15"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12231801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458301","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":"Sleep-wake cycle and 24-h motor activity in early-mid Huntington's disease patients: An actigraphy-based study.","authors":"Cesa Scaglione, Maria Vitiello, Lorenzo Tonetti, Sara Giovagnoli, Giorgio Barletta, Giovanna Calandra-Buonaura, Pietro Guaraldi, Felice Di Laudo, Vincenzo Natale, Federica Provini","doi":"10.1177/18796397241287227","DOIUrl":"10.1177/18796397241287227","url":null,"abstract":"<p><p><b>Background:</b> Disrupted 24-h sleep-wake and rest-activity cycles are known common features in Huntington's disease (HD) patients; however, critical periods during the 24-h cycle have been less studied. <b>Objective:</b> To analyze the differences between early-mid stage HD patients and healthy controls (HC) in sleep patterns and 24-h motor activity by using actigraphic monitoring. <b>Methods:</b> Twenty HD patients (13 females; mean age ± SD 56.45 ± 16.94) at early-mid stage of the disease and 20 HC were actigraphically monitored for a week. We applied the Functional Linear Modeling (FLM) to analyze motor activity from the actigraphic data. We analyzed parameters regarding both the time spent in bed and out of bed; get-up time (GUT); time in bed (TIB); midpoint of sleep (MS); sleep motor activity (SMA); sleep onset latency (SOL); total sleep time (TST); wake after sleep onset (WASO); sleep efficiency (SE); number and duration of awakenings (AWK); diurnal motor activity (DMA) and diurnal total sleep time (DTST). <b>Results:</b> Ten patients were in Stage I, 6 in Stage II and 4 in Stage III. HD patients presented lower SE and higher TIB, SOL, WASO, AWK and AWK > 5 min in comparison to HC. Moreover, higher motor activity was observed in patients with HD, in particular between 2:15 and 4:00 am, from around 40 min prior to bedtime until 20 min after bedtime, and from around 20 min prior to get-up time until 50 min after get-up time. <b>Conclusions:</b> Actigraphy documented a specific 24-h motor pattern in HD, potentially constituting a disease signature.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":"13 4","pages":"501-509"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458184","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":"Are people living with Huntington's disease experiencing person-centered integrated care?","authors":"Sandra Bartolomeu Pires, Dorit Kunkel, Nicholas Goodwin, Sally Dace, David Culliford, Christopher Kipps, Mari Carmen Portillo","doi":"10.1177/18796397241288449","DOIUrl":"10.1177/18796397241288449","url":null,"abstract":"<p><p><b>Background:</b> Huntington's disease (HD) is among the most complex long-term neurological conditions, necessitating care and management from multiple partners within and beyond the health sector. However, there is a paucity of evidence describing how individuals receive this multifaceted care and whether current care provision adequately meets their needs. <b>Objective:</b> To understand if current care provision is meeting the complex needs of people living with HD in England and assess their perceived need for integrated care. <b>Methods:</b> A cross-sectional survey was co-designed with patient and public representatives, as part of a mixed-methods study to explore what integrated care means for people living with HD. The survey was distributed online and via charities, collecting quantitative and qualitative data. Descriptive statistics and content analysis were performed. <b>Results:</b> A total of 153 people, from 45 counties in England, participated in the survey. When assessing person-centered coordinated care, 65% of respondents rated their care as very poor, poor, or expressed a neutral opinion; carers reported the lowest scores. Although 58% of the participants said it was extremely important to have a care coordinator, only 19% of people reported having one, with these coordinators being identified in only 40% of the counties. Nevertheless, people with access to a care coordinator reported markedly improved care experiences. <b>Conclusions:</b> People living with HD commonly report fragmented care, geographical inequalities in care access, and unmet complex needs. Future research should focus on developing an HD integrated care model tailored to address these complex needs, including an evaluation of the cost-effectiveness of an HD care coordinator.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":"13 4","pages":"535-546"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458149","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":"Changes in 24(S)-Hydroxycholesterol Are Associated with Cognitive Performance in Early Huntington's Disease: Data from the TRACK and ENROLL HD Cohorts.","authors":"Sarah M Gray, Jing Dai, Anne C Smith, Jacob T Beckley, Negah Rahmati, Michael C Lewis, Michael C Quirk","doi":"10.3233/JHD-240030","DOIUrl":"10.3233/JHD-240030","url":null,"abstract":"<p><strong>Background: </strong>There is evidence for dysregulated cholesterol homeostasis in Huntington's disease (HD). The brain-specific cholesterol metabolite 24(S)-hydroxycholesterol (24(S)-OHC) is decreased in manifest HD. 24(S)-OHC is an endogenous positive allosteric modulator (PAM) of the N-methyl-D-aspartate (NMDA) receptor, suggesting lower 24(S)-OHC may contribute to NMDA receptor hypofunction in HD. We hypothesized changes in 24(S)-OHC would be associated with cognitive impairment in early HD.</p><p><strong>Objective: </strong>To determine the interactions between oxysterols (24(S)-OHC, 25-OHC, and 27-OHC) at the NMDA receptor, the plasma levels of these oxysterols, and how these levels relate to cognitive performance.</p><p><strong>Methods: </strong>An <i>in vitro</i> competition assay was used to evaluate interactions at the NMDA receptor, liquid chromatography coupled tandem mass spectrometry (LC-MS/MS) was used to measure plasma 24(S)-OHC, 25-OHC, and 27-OHC levels, and correlation analyses investigated their relationship to performance on cognitive endpoints in TRACK and ENROLL-HD (NCT01574053).</p><p><strong>Results: </strong><i>In vitro</i>, 25-OHC and 27-OHC attenuated the PAM activity of 24(S)-OHC on the NMDA receptor. Lower plasma 24(S)-OHC levels and 24(S)/25-OHC ratios were detected in participants with early HD. Moderate and consistent associations were detected between plasma 24(S)/25-OHC ratio and performance on Stroop color naming, symbol digit modality, Trails A/B, and emotion recognition. Little association was observed between the ratio and psychiatric or motor endpoints, suggesting specificity for the relationship to cognitive performance.</p><p><strong>Conclusions: </strong>Our findings support growing evidence for dysregulated CNS cholesterol homeostasis in HD, demonstrate a relationship between changes in oxysterols and cognitive performance in HD, and propose that NMDA receptor hypofunction may contribute to cognitive impairment in HD.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"449-465"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289159","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}