Journal of Huntington's disease最新文献

{"title":"An Overview of Specialist Services for Huntington's Disease in the United Kingdom.","authors":"Rosa Willock, Hugh Rickards, Anne E Rosser, Alistair Haw, Cath Stanley, Pushpa Hossain, Idaira Rodríguez-Santana, Maria Doherty, Rachel Blair, Wendy Kane","doi":"10.3233/JHD-220560","DOIUrl":"10.3233/JHD-220560","url":null,"abstract":"<p><strong>Background: </strong>Huntington's disease (HD) is a rare inherited neurodegenerative disorder characterized by complex evolving needs that change as the condition progresses. There is limited understanding about the organization of HD clinical services and their resourcing in the United Kingdom (UK).</p><p><strong>Objective: </strong>To understand the organization and resourcing of specialist HD services for people with HD (PwHD) in the UKMethods:This cross-sectional study collected quantitative data via on online survey, and qualitative data via telephone semi-structured interviews. Descriptive statistics were used to describe quantitative outcomes, and qualitative results were analyzed using content analysis.</p><p><strong>Results: </strong>A total of 31 specialist services for HD were identified. Of the 27 services that completed the online survey, 23 had an active multidisciplinary team of healthcare professionals (HCPs) and were led primarily by a mental health trust (26%) or tertiary referral hospital (26%). Specialist services offered outpatient clinics (96%), outreach in the community (74%), telemedicine (70%), inpatient beds (26%) and satellite clinics (26%). Many services indicated that their capacity (ability to see patients as often as needed with current resources) was difficult, with some services reporting more difficulty at the early or later stages of HD. Key resourcing gaps were identified with access to facilities, HCPs and referral networks.</p><p><strong>Conclusions: </strong>This research highlights the variation in organization and capacity within individual HD services as well as current resourcing and gaps in access that influence this capacity. Further research should be done to understand the impact of service organization and current resourcing gaps in access on the quality of care provided for PwHD in the UK.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":"12 4","pages":"363-370"},"PeriodicalIF":3.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10741324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138805926","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":"Age-Dependent Increase in Tau Phosphorylation at Serine 396 in Huntington's Disease Prefrontal Cortex.","authors":"Tiziana Petrozziello, Sommer S Huntress, Ayleen L Castillo-Torres, James P Quinn, Theresa R Connors, Corinne A Auger, Alexandra N Mills, Spencer E Kim, Sophia Liu, Farah Mahmood, Adel Boudi, Muzhou Wu, Ellen Sapp, Pia Kivisäkk, Shekar R Sunderesh, Mahmoud A Pouladi, Steven E Arnold, Bradley T Hyman, H Diana Rosas, Marian DiFiglia, Ricardo Mouro Pinto, Kimberly Kegel-Gleason, Ghazaleh Sadri-Vakili","doi":"10.3233/JHD-230588","DOIUrl":"10.3233/JHD-230588","url":null,"abstract":"<p><strong>Background: </strong>To date, it is still controversial whether tau phosphorylation plays a role in Huntington's disease (HD), as previous studies demonstrated either no alterations or increases in phosphorylated tau (pTau) in HD postmortem brain and mouse models.</p><p><strong>Objective: </strong>The goal of this study was to determine whether total tau and pTau levels are altered in HD.</p><p><strong>Methods: </strong>Immunohistochemistry, cellular fractionations, and western blots were used to measure total tau and pTau levels in a large cohort of HD and control postmortem prefrontal cortex (PFC). Furthermore, western blots were performed to assess tau, and pTau levels in HD and control isogenic embryonic stem cell (ESC)-derived cortical neurons and neuronal stem cells (NSCs). Similarly, western blots were used to assess tau and pTau levels in HttQ111 and transgenic R6/2 mice. Lastly, total tau levels were assessed in HD and healthy control plasma using Quanterix Simoa assay.</p><p><strong>Results: </strong>Our results revealed that, while there was no difference in total tau or pTau levels in HD PFC compared to controls, the levels of tau phosphorylated at S396 were increased in PFC samples from HD patients 60 years or older at time of death. Additionally, tau and pTau levels were not changed in HD ESC-derived cortical neurons and NSCs. Similarly, total tau or pTau levels were not altered in HttQ111 and transgenic R6/2 mice compared to wild-type littermates. Lastly, tau levels were not changed in plasma from a small cohort of HD patients compared to controls.</p><p><strong>Conclusions: </strong>Together these findings demonstrate that pTau-S396 levels increase significantly with age in HD PFC.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"267-281"},"PeriodicalIF":2.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11823699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10293975","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":"Introduction to the special issue on sleep and circadian rhythms in Huntington's disease.","authors":"Jenny Morton","doi":"10.3233/JHD-239003","DOIUrl":"https://doi.org/10.3233/JHD-239003","url":null,"abstract":"","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":"12 2","pages":"85-87"},"PeriodicalIF":3.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/45/09/jhd-12-jhd239003.PMC10473055.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10137359","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":"Oculomotor Abnormalities in a Sheep (Ovis aries) Model of Huntington's Disease: Towards a Biomarker for Assessing Therapeutic Efficacy.","authors":"Sebastian D McBride,&nbsp;Jan Ober,&nbsp;Jacek Dylak,&nbsp;William Schneider,&nbsp;A Jennifer Morton","doi":"10.3233/JHD-230584","DOIUrl":"10.3233/JHD-230584","url":null,"abstract":"<p><strong>Background: </strong>Huntington's disease (HD) is characterized by a loss of control of motor function that causes the presence of abnormal eye movements at early stages.</p><p><strong>Objective: </strong>To determine if, compared to normal sheep, HD sheep have abnormal eye movements.</p><p><strong>Methods: </strong>We measured eye movements in a transgenic sheep (Ovis aries) model of HD using a purpose-built, head-mounted sheep oculometer. This allows us to measure saccades without the need for either behavioral training or head fixation. At the age of testing (6 years old), the HD sheep were pre-manifest. We used 21 sheep (11 HD, 10 normal).</p><p><strong>Results: </strong>We found small but significant differences in eye movements between normal (control) and HD sheep during vestibular ocular reflex (VOR)- and vestibular post-rotational nystagmus (PRN)-based tests.</p><p><strong>Conclusions: </strong>Two measures were identified that could distinguish normal from HD sheep; the number of PRN oscillations when tested in the dark and the gain (eye movement to head movement ratio) during the VOR when tested in the light. To our knowledge, this is the first study in which eye movements have been quantified in sheep. It demonstrates the feasibility of measuring and quantifying human-relevant eye movements in this species. The HD-relevant deficits show that even in 'premanifest' sheep there are measurable signs of neurological dysfunction that are characterized by loss of control of eye movements.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"189-200"},"PeriodicalIF":3.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10651987","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":"Graphomotor Dysfluency as a Predictor of Disease Progression in Premanifest Huntington's Disease.","authors":"Michael Caligiuri,&nbsp;Braden Culbert,&nbsp;Nikita Prasad,&nbsp;Chase Snell,&nbsp;Andrew Hall,&nbsp;Anna Smirnova,&nbsp;Emma Churchill,&nbsp;Jody Corey-Bloom","doi":"10.3233/JHD-230562","DOIUrl":"10.3233/JHD-230562","url":null,"abstract":"<p><strong>Background: </strong>Prior studies have relied on conventional observer-based severity ratings such as the Unified Huntington's Disease Rating Scale (UHDRS) to identify early motor markers of decline in Huntington's disease (HD).</p><p><strong>Objective: </strong>The present study examined the predictive utility of graphomotor measures handwriting and drawing movements.</p><p><strong>Methods: </strong>Seventeen gene-positive premanifest HD subjects underwent comprehensive clinical, cognitive, motor, and graphomotor assessments at baseline and at follow-up intervals ranging from 9-36 months. Baseline graphomotor assessments were subjected to linear multiple regression procedures to identify factors associated with change on the comprehensive UHDRS index.</p><p><strong>Results: </strong>Subjects were followed for an average of 21.2 months. Three multivariate regression models based on graphomotor variables derived from a complex loop task, a maximum speed circle drawing task and a combined task returned adjusted R2 coefficients of 0.76, 0.71, and 0.80 respectively accounting for a significant portion of the variability in cUHDRS change score. The best-fit model based on the combined tasks indicated that greater decline on the cUHDRS was associated with increased pen movement dysfluency and stroke-stroke variability at baseline.</p><p><strong>Conclusion: </strong>Performance on multiple measures of graphomotor dysfluency assessed during the premanifest or prodromal stage in at-risk HD individuals was associated with decline on a multidimensional index of HD morbidity preceding an HD diagnosis.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"283-292"},"PeriodicalIF":3.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9464153","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":"Sleep, Circadian Rhythms, and Cognitive Dysfunction in Huntington's Disease.","authors":"Emily S Fitzgerald,&nbsp;Julie C Stout,&nbsp;Yifat Glikmann-Johnston,&nbsp;Clare Anderson,&nbsp;Melinda L Jackson","doi":"10.3233/JHD-230578","DOIUrl":"10.3233/JHD-230578","url":null,"abstract":"<p><strong>Background: </strong>In healthy people, sleep and circadian disruption are linked to cognitive deficits. People with Huntington's disease (HD), who have compromised brain function and sleep and circadian disturbances, may be even more susceptible to these cognitive effects.</p><p><strong>Objective: </strong>To conduct a comprehensive review and synthesis of the literature in HD on the associations of cognitive dysfunction with disturbed sleep and circadian rhythms.</p><p><strong>Methods: </strong>We searched MEDLINE via OVID, CINAHL Plus, EMBASE via OVID, and PubMed in May 2023. The first author then screened by title and abstract and conducted a full review of remaining articles.</p><p><strong>Results: </strong>Eight studies investigating the influence of sleep and/or circadian rhythms on cognitive function in HD were found. In manifest HD, poorer sleep was associated with worse cognitive function. For behavioral 24-hour (circadian) rhythms, two studies indicated that later wake times correlated with poorer cognitive function. No reported studies in HD examined altered physiological 24-hour (circadian) rhythms and cognitive impairment.</p><p><strong>Conclusion: </strong>Some associations exist between poor sleep and cognitive dysfunction in manifest HD, yet whether these associations are present before clinical diagnosis is unknown. Whether circadian disturbances relate to cognitive impairment in HD also remains undetermined. To inform sleep and circadian interventions aimed at improving cognitive symptoms in HD, future research should include a range of disease stages, control for external factors, and utilize robust cognitive batteries targeted to the aspects of cognitive function known to be adversely affected in HD.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"293-304"},"PeriodicalIF":3.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10406789","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":"10.3233/JHD-229008","DOIUrl":"https://doi.org/10.3233/JHD-229008","url":null,"abstract":"","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2022-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10435526","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":"Abstracts of the 29th Annual Meeting of the Huntington Study Group, November 3-5, 2022, Tampa, Florida.","authors":"","doi":"10.3233/jhd-229005","DOIUrl":"https://doi.org/10.3233/jhd-229005","url":null,"abstract":"","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":"11 s1 1","pages":"S1-S55"},"PeriodicalIF":3.1,"publicationDate":"2022-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47997468","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":"10.3233/jhd-229004","DOIUrl":"https://doi.org/10.3233/jhd-229004","url":null,"abstract":"","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2022-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48456364","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":"The Lived Experiences of Depression in Huntington's Disease: A Qualitative Study.","authors":"H. Bilal, Narelle Warren, Pinithi Dahanayake, W. Kelso, Farrand Sarah, J. Stout","doi":"10.3233/jhd-220537","DOIUrl":"https://doi.org/10.3233/jhd-220537","url":null,"abstract":"BACKGROUND\u0000Depression is a common neuropsychiatric syndrome in Huntington's disease (HD) and has debilitating consequences, including poorer sleep, exacerbation of cognitive and functional decline, and suicidality. To date, no published studies have documented the lived experience of depression in HD, despite clinical evidence that depression may be experienced differently in HD compared to the general population.\u0000\u0000\u0000OBJECTIVE\u0000The aim of this study was to investigate the lived experiences of depression in people with the CAG expansion for HD using qualitative methods.\u0000\u0000\u0000METHODS\u0000We conducted semi-structured interviews with HD CAG expansion carriers who had current or previous experiences of depression, until data saturation was achieved. This resulted in interviews from 17 HD CAG expansion carriers (11 premanifest, 6 manifest) which were analyzed using thematic analysis.\u0000\u0000\u0000RESULTS\u0000The four key themes that emerged related to the temporal characteristics of depression in HD, the qualitative changes associated with depression, psychosocial stressors perceived to contribute to depression, and the perception of depression as an endogenous feature of HD.\u0000\u0000\u0000CONCLUSION\u0000This study provides an enriched understanding of the unique characteristics of depression in HD, and the attributions that CAG expansion carriers make for their depression symptoms. The themes identified in this study can be used to guide more targeted assessment and treatment of depression in HD.","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2022-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46960123","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}