Sebastian D McBride, Jan Ober, Jacek Dylak, William Schneider, A Jennifer Morton
{"title":"Oculomotor Abnormalities in a Sheep (Ovis aries) Model of Huntington's Disease: Towards a Biomarker for Assessing Therapeutic Efficacy.","authors":"Sebastian D McBride, Jan Ober, Jacek Dylak, William Schneider, 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":null,"pages":null},"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}
Emily S Fitzgerald, Julie C Stout, Yifat Glikmann-Johnston, Clare Anderson, Melinda L Jackson
{"title":"Sleep, Circadian Rhythms, and Cognitive Dysfunction in Huntington's Disease.","authors":"Emily S Fitzgerald, Julie C Stout, Yifat Glikmann-Johnston, Clare Anderson, 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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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}
H. Bilal, Narelle Warren, Pinithi Dahanayake, W. Kelso, Farrand Sarah, J. Stout
{"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":null,"pages":null},"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}
C. Estévez-Fraga, F. B. Rodrigues, S. Tabrizi, E. Wild
{"title":"Huntington's disease clinical trials corner: April 2022.","authors":"C. Estévez-Fraga, F. B. Rodrigues, S. Tabrizi, E. Wild","doi":"10.3233/jhd-229002","DOIUrl":"https://doi.org/10.3233/jhd-229002","url":null,"abstract":"In this edition of the Huntington's Disease Clinical Trials Corner we expand on GENERATION HD1, PRECISION-HD1 and PRECISION-HD2, SELECT-HD, and VIBRANT-HD trials, and list all currently registered and ongoing clinical trials in Huntington's disease.","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43804710","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}
Colby L. Chase, B. Yashar, Chandler Swope, R. Albin, W. Uhlmann
{"title":"Searching for Answers: Information-Seeking by Young People At-Risk for Huntington’s Disease","authors":"Colby L. Chase, B. Yashar, Chandler Swope, R. Albin, W. Uhlmann","doi":"10.3233/JHD-210523","DOIUrl":"https://doi.org/10.3233/JHD-210523","url":null,"abstract":"Background: Health information-seeking is a coping strategy used globally by individuals with a personal or family history of a medical condition, including Huntington’s disease (HD). Objective: We sought to ascertain information-seeking practices of young people who grew up at-risk for HD. Methods: Participants ages 18–25 were recruited from HD support organizations. An online 96-item survey assessed information-seeking motivations and timing as well as information topics accessed, sources, and needs. Results: Fifty young adults (mean age 22.2 years) who grew up at-risk for HD responded. HD had been generally kept a secret (35.4%) or talked about but difficult to bring up (43.8%) in many families. Most (78.0%) became aware of HD in their family before age 15. Few (7.1%) received information resources at the time of disclosure. Most (68.1%) first sought information independently online, half within a week of disclosure. Respondents were motivated to understand the potential impact of HD on their personal lives and family members, obtain general information about the condition, and learn about treatments and research. Most sought information on clinical features and inheritance with > 80% interested in information on symptoms and personal risk and > 70% about having children. Conclusion: Limited information is provided to young people when first informed about HD in their families leading to independent, mostly online information-seeking. Information is used to build knowledge about HD to facilitate coping and life planning. Healthcare providers can direct young people to reliable resources and guide parents in talking with children to ensure that information needs are met.","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41834803","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":"Nursing Approaches and Perceived Quality of Life in Advanced Stage Huntington's Disease Patients.","authors":"J. Engels, E. van Duijn","doi":"10.3233/jhd-210481","DOIUrl":"https://doi.org/10.3233/jhd-210481","url":null,"abstract":"BACKGROUND\u0000Long-term Huntington's disease (HD) care is offered in specialized inpatient nursing home units with a focus on individually perceived quality of life (QoL). This is shaped in daily care and interaction, which is often abstract and intangible. Furthermore, different perspectives are involved and may vary.\u0000\u0000\u0000OBJECTIVE\u0000To explore and describe perceived QoL of HD patients from three perspectives: manifest HD patients, family members, and nursing staff.\u0000\u0000\u0000METHODS\u000036 patients, 11 family members, and 30 nurses participated in this qualitative study by means of individual interviews and systematic qualitative observations on three units.\u0000\u0000\u0000RESULTS\u0000Preservation of identity and autonomy is important for patients. Patients struggle with increasing dependence, and try to cope with the impact, uncertainty, and progressive nature of the disease. All participants emphasize the focus on \"being human, not just a patient\". Both patients and family members mention the difficulty of dealing with altered behavior and loss of control. Patients are reliant on a relational approach, and an attitude of unconditional acceptance, trust, and understanding support by the nurses. Nursing staff help patients to focus on preserved abilities, and to continue to engage in personalized preferred social activities. Specific qualifications of the nurses were of major influence on QoL for HD patients.\u0000\u0000\u0000CONCLUSION\u0000This study shows, from the patient as well as family member and nursing staff perspectives, that caring for HD patients requires specific knowledge and skills. Particular nursing approaches and attitude and qualifications of the nursing staff in residential HD care improves the perceived QoL of patients.","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44086734","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}
Olivia S. Brumfield, Christine Zizzi, N. Dilek, Danae Alexandrou, Alistair Glidden, S. Rosero, Jennifer S. Weinstein, J. Seabury, A. Kaat, Michael P McDermott, E. Dorsey, C. Heatwole
{"title":"The Huntington's Disease Health Index: Initial Evaluation of a Disease-Specific Patient Reported Outcome Measure.","authors":"Olivia S. Brumfield, Christine Zizzi, N. Dilek, Danae Alexandrou, Alistair Glidden, S. Rosero, Jennifer S. Weinstein, J. Seabury, A. Kaat, Michael P McDermott, E. Dorsey, C. Heatwole","doi":"10.3233/JHD-210506","DOIUrl":"https://doi.org/10.3233/JHD-210506","url":null,"abstract":"BACKGROUND\u0000When developed properly, disease-specific patient reported outcome measures have the potential to measure relevant changes in how a patient feels and functions in the context of a therapeutic trial. The Huntington's Disease Health Index (HD-HI) is a multifaceted disease-specific patient reported outcome measure (PROM) designed specifically to satisfy previously published FDA guidance for developing PROMs for product development and labeling claims.\u0000\u0000\u0000OBJECTIVE\u0000In preparation for clinical trials, we examine the validity, reliability, clinical relevance, and patient understanding of the Huntington's Disease Health Index (HD-HI).\u0000\u0000\u0000METHODS\u0000We partnered with 389 people with Huntington's disease (HD) and caregivers to identify the most relevant questions for the HD-HI. We subsequently utilized two rounds of factor analysis, cognitive interviews with fifteen individuals with HD, and test-retest reliability assessments with 25 individuals with HD to refine, evaluate, and optimize the HD-HI. Lastly, we determined the capability of the HD-HI to differentiate between groups of HD participants with high versus low total functional capacity score, prodromal versus manifest HD, and normal ambulation versus mobility impairment.\u0000\u0000\u0000RESULTS\u0000HD participants identified 13 relevant and unique symptomatic domains to be included as subscales in the HD-HI. All HD-HI subscales had a high level of internal consistency and reliability and were found by participants to have acceptable content, relevance, and usability. The total HD-HI score and each subscale score statistically differentiated between groups of HD participants with high versus low disease burden.\u0000\u0000\u0000CONCLUSION\u0000Initial evaluation of the HD-HI supports its validity and reliability as a PROM for assessing how individuals with HD feel and function.","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45952447","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}