Journal of Huntington's disease最新文献

{"title":"Sleep Disorders and Circadian Disruption in Huntington's Disease.","authors":"Sandra Saade-Lemus,&nbsp;Aleksandar Videnovic","doi":"10.3233/JHD-230576","DOIUrl":"https://doi.org/10.3233/JHD-230576","url":null,"abstract":"<p><p>Sleep and circadian alterations are common in patients with Huntington's disease (HD). Understanding the pathophysiology of these alterations and their association with disease progression and morbidity can guide HD management. We provide a narrative review of the clinical and basic-science studies centered on sleep and circadian function on HD. Sleep/wake disturbances among HD patients share many similarities with other neurodegenerative diseases. Overall, HD patients and animal models of the disease present with sleep changes early in the clinical course of the disease, including difficulties with sleep initiation and maintenance leading to decreased sleep efficiency, and progressive deterioration of normal sleep architecture. Despite this, sleep alterations remain frequently under-reported by patients and under-recognized by health professionals. The degree of sleep and circadian alterations has not consistently shown to be CAG dose-dependent. Evidence based treatment recommendations are insufficient due to lack of well-designed intervention trials. Approaches aimed at improving circadian entrainment, such as including light therapy, and time-restricted feeding have demonstrated a potential to delay symptom progression in some basic HD investigations. Larger study cohorts, comprehensive assessment of sleep and circadian function, and reproducibility of findings are needed in future in order to better understand sleep and circadian function in HD and to develop effective treatments.</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":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b2/11/jhd-12-jhd230576.PMC10473087.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10142769","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":"Altered Adipocyte Cell Size Distribution Prior to Weight Loss in the R6/2 Model of Huntington's Disease.","authors":"Elna Dickson,&nbsp;Claes Fryklund,&nbsp;Rana Soylu-Kucharz,&nbsp;Marie Sjögren,&nbsp;Karin G Stenkula,&nbsp;Maria Björkqvist","doi":"10.3233/JHD-230587","DOIUrl":"10.3233/JHD-230587","url":null,"abstract":"<p><strong>Background: </strong>Metabolic alterations contribute to disease onset and prognosis of Huntington's disease (HD). Weight loss in the R6/2 mouse model of HD is a consistent feature, with onset in mid-to-late stage of disease.</p><p><strong>Objective: </strong>In the present study, we aimed to investigate molecular and functional changes in white adipose tissue (WAT) that occur at weight loss in R6/2 mice. We further elaborated on the effect of leptin-deficiency and early obesity in R6/2 mice.</p><p><strong>Methods: </strong>We performed analyses at 12 weeks of age; a time point that coincides with the start of weight loss in our R6/2 mouse colony. Gonadal (visceral) and inguinal (subcutaneous) WAT depot weights were monitored, as well as adipocyte size distribution. Response to isoprenaline-stimulated glycerol release and insulin-stimulated glucose uptake in adipocytes from gonadal WAT was assessed.</p><p><strong>Results: </strong>In R6/2 mice, WAT depot weights were comparable to wildtype (WT) mice, and the response to insulin and isoprenaline in gonadal adipocytes was unaltered. Leptin-deficient R6/2 mice exhibited distinct changes compared to leptin-deficient WT mice. At 12 weeks, female leptin-deficient R6/2 mice had reduced body weight accompanied by an increased proportion of smaller adipocytes, while in contrast; male mice displayed a shift towards larger adipocyte sizes without a significant body weight reduction at this timepoint.</p><p><strong>Conclusions: </strong>We here show that there are early sex-specific changes in adipocyte cell size distribution in WAT of R6/2 mice and leptin-deficient R6/2 mice.</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":"10634637","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-239006","DOIUrl":"https://doi.org/10.3233/JHD-239006","url":null,"abstract":"","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":"41135634","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":"Frailty and Associated Environmental Factors Only Have Small Effects on Age of Onset in Huntington's Disease.","authors":"Niroshan Jeyakumar, Sarah N Hilmer, Armando Teixeira-Pinto, Clement T Loy","doi":"10.3233/JHD-230572","DOIUrl":"10.3233/JHD-230572","url":null,"abstract":"<p><strong>Background: </strong>Over one third of age of onset variation in Huntington's disease is unexplained by CAG repeat length. In Alzheimer's disease, frailty partly modulates the relationship between neuropathology and dementia.</p><p><strong>Objective: </strong>We investigated whether a multi-domain frailty index, reflecting non-genetic factors in Huntington's disease, similarly modulates the relationship between CAG repeat length and age of onset.</p><p><strong>Methods: </strong>We created a frailty index assessing comorbidities, substance abuse, polypharmacy, and education. We applied multiple linear regression models to 2,741 subjects with manifest Huntington's disease from the Enroll-HD cohort study, including 729 subjects with late-onset (post-60 years) disease, using frailty index or constituent item scores and CAG repeat length as independent variables. We used actual and \"residual\" ages of onset (difference between actual and CAG-based predicted onset) as dependent variables, the latter offsetting the increased time available to accumulate comorbidities in older subjects.</p><p><strong>Results: </strong>Higher frailty index scores were associated with significantly lower residual ages of onset in the late-onset subgroup (p = 0.03), though the effect was small (R2 = 0.27 with frailty as a predictor vs. 0.26 without). Number of comorbidities was also associated with significantly lower residual ages of onset in the late-onset subgroup (p = 0.04). Drug abuse and smoking were associated with significantly earlier ages of onset in the whole cohort (p < 0.01, p = 0.02) and late-onset subgroup (p < 0.01, p = 0.03).</p><p><strong>Conclusions: </strong>The impact of non-genetic factors on age of onset, assessed using a frailty index or separately, in Huntington's disease is limited.</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":"138440811","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 and the History of Sleep.","authors":"Alice R Wexler","doi":"10.3233/JHD-230568","DOIUrl":"https://doi.org/10.3233/JHD-230568","url":null,"abstract":"Long before I first heard the words Huntington’s disease, I had trouble sleeping: difficulty falling asleep, problems staying asleep. Even as a kid I worried about sleep. My therapist father would comfort me, telling me not to worry; resting in bed, he would say, was almost like sleeping: not the advice sleep experts give today. He too had trouble sleeping. My sister Nancy, on the other hand, has been a gifted sleeper most her life. From the time she was little, she could fall asleep instantly at night, in the car on road trips, and on planes during long flights. Mostly she stayed awake and alert during the day. Her sleep changed as Huntington’s symptoms emerged, long before her diagnosis. She began falling asleep during the day, dozing off at meetings or in front of her computer. I attributed her daytime sleepiness to her overbooked schedule and lack of time in bed due to heavy professional and social commitments. With her diagnosis—followed several months later by the pandemic—she began staying up extremely late; she awoke more often during the night and had more difficulty returning to sleep; she slept late, sometimes past noon, though once awake, she usually remained so. No matter if her partner without Huntington’s followed a regular timetable, going to bed and awakening at more or less his typical workday hour, Nancy’s pattern did not adapt. Even as her Huntington’s progresses, my sister remains a free spirit. With few externally-imposed commitments, she can follow her circadian rhythms wherever they take her, though not without pressures from others in the household to follow a more conventional","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":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/bf/58/jhd-12-jhd230568.PMC10473129.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10512059","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":"Supporting Huntington's Disease Families Through the Ups and Downs of Clinical Trials.","authors":"Kelly M Andrew,&nbsp;Leora M Fox","doi":"10.3233/JHD-230565","DOIUrl":"https://doi.org/10.3233/JHD-230565","url":null,"abstract":"<p><p>Recent years have been turbulent ones for the Huntington's disease (HD) community. Three clinical trials for HD, including the first Phase 3 trial of a potentially disease modifying genetic therapy for HD, were all brought to a halt in March of 2021. 2022 brought more study roadblocks and an additional trial termination. As HD science progresses and larger scale trials become more frequent in the community, HD families are faced with the difficult reality that clinical research rarely results in a new drug hitting the market. To better understand how the HD community can be prepared for the ups and downs that accompany an expanding clinical research pipeline, the Huntington's Disease Society of America (HDSA) spoke with members of the Huntington's Disease Coalition for Patient Engagement (HD-COPE). This group of global advocates led by HDSA and the Huntington's Society of Canada (HSC) collaborates with pharmaceutical companies to ensure that HD voices are represented in the planning of clinical trials. These conversations allowed HDSA to summarize how the HD community can be best supported through the clinical research process in three key areas: engagement, support, and education.</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":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0e/ae/jhd-12-jhd230565.PMC10200140.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10022276","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":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":"10293975","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":"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":null,"pages":null},"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":"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":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":"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":"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":null,"pages":null},"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}