Journal of Huntington's disease最新文献

Background: The Huntington's Disease (HD) Everyday Functioning (Hi-DEF) is a new patient-reported outcome (PRO) instrument designed to measure the impact of cognitive impairment on daily functioning in the early stages of HD.

Objective: To assess the measurement properties and finalize item content of the Hi-DEF.

Methods: A cross-sectional, observational psychometric validation study was conducted among individuals with early stages of HD at 9 US centers of excellence. Rasch Measurement Theory (RMT) analysis of the initial draft version of the Hi-DEF (47 items) and subscales (i.e., 'Home', 'At work', 'Driving', and 'Communication') was conducted to examine measurement properties including sample-to-scale targeting, suitability of response scale (ordering of response thresholds), scale cohesiveness (item fit), local independence, and person fit.

Results: 151 participants (mean age 47 years (SD 12), 59% female) were included. Seven items were removed based on dependency and item fit. The remaining 40-item version of the Hi-DEF demonstrated good measurement properties. Across the four subscales, targeting ranged from 49-70% (72% full scale), reliability ascertained by person separation index ranged from 0.53-0.87 (0.92 full scale), response scales were ordered for 25-100% of items (75% full scale), 0-12% items displayed misfit (2% full scale), and 0-1% (2% full scale) item pairs displayed dependency.

Conclusions: Our study supports the psychometric integrity of the Hi-DEF as a reliable and valid new PRO instrument designed to assess the impact of cognitive impairment on daily functioning in the early stages of HD. Future work will evaluate the external validity and utility in clinical trial applications.

Background: Huntington's disease (HD) presents patients and individuals at risk for HD with significant levels of stress. However, relatively little research has examined how individuals cope with stress related to the disease or the association of specific coping strategies with psychological symptoms.

Objective: This study examined the ways in which HD patients and at-risk individuals cope with HD-related stress using a control-based model of coping and the association of coping strategies with symptoms of depression and anxiety.

Methods: HD patients (n = 49) and at-risk individuals (n = 76) completed the Responses to Stress Questionnaire - Huntington's Disease Version to assess coping strategies in response to HD-related stress, as well as standardized measures of depression and anxiety symptoms. Patient health records were accessed to obtain information related to disease characteristics.

Results: Patients and at-risk individuals reported using comparable levels of primary control coping, secondary control coping, and disengagement coping strategies. In linear regression analyses, only secondary control coping was significantly associated with lower depression (β= -0.62, p < 0.001) and anxiety (β= -0.59, p < 0.001) symptoms in patients and at-risk individuals (β= -0.55, p < 0.001 and β= -0.50, p < 0.001, respectively).

Conclusions: Secondary control coping may be beneficial for both HD patients and at-risk individuals. Future research using the control-based model of coping in longitudinal studies with the HD population is needed, and future interventions could test the effects of cognitive reframing and acceptance as coping strategies for families affected by HD.

Huntington's disease (HD) is a rare neurodegenerative disorder with a distinct phenotype, including involuntary movements, cognitive decline, and behavioral disturbances. Sleep disorder include insomnia, increased sleep onset latency, decrease in total sleep time with frequent nocturnal awakenings and excessive daytime sleepiness. Increased sleep motor activities and abnormal nocturnal agitation have been increasingly recognized as an important component affecting negatively the sleep quality. Here, we report a case of an intensification of diurnal choreic movement during the night, notably during REM-sleep in a patient with manifest HD. This case highlights the diversity of nocturnal sleep motor disorders encountered in HD.

Background: Huntington's disease (HD) is a neurodegenerative disorder marked by cognitive impairment, movement abnormalities, and behavioral disturbances. The Stroop Color Word Test (SCWT) is a widely used tool to detect cognitive decline in HD. Variations in SCWT formats-horizontal (original) and vertical (Golden)-may influence performance, given HD's impact on cognitive and oculomotor abilities.

Objective: This study aimed to compare the effectiveness of the horizontal and Golden vertical SCWT formats in detecting cognitive decline in HD, and to determine how performance may have been influenced by eye movement abnormalities.

Methods: Forty-five participants with genetically confirmed HD were recruited. Both SCWT formats were administered to each participant in a counterbalanced fashion. Individual performance of all three sections on each format was standardized across 2 different norms. Raw and normed scores on each variation were compared and correlated with eye movement ratings on the Unified Huntington's Disease Rating Scale.

Results: The Golden variation elicited significantly slower responses, particularly in the Word Reading section, across two benchmark norms. Statistical analysis revealed significant performance differences between the two formats. Correlations between vertical eye movement ratings and performance on the Golden SCWT were highly significant, highlighting the impact of oculomotor coordination on cognitive assessments in HD.

Conclusion: This study underscores the importance of considering test format in cognitive assessments for HD. The Golden vertical SCWT demonstrates increased sensitivity in detecting deficits in HD, possibly linked to vertical saccade abnormalities. These insights are important for improving the sensitivity of cognitive assessments and monitoring disease progression in HD research and clinical practice.

Background: People with Huntington's disease (HD) exhibit neurocognitive alterations throughout the disease, including deficits in social cognitive processes such as Theory of Mind (ToM).

Objective: The aim is to identify methodologies and ToM instruments employed in HD, alongside relevant findings, within the scientific literature of the past two decades.

Methods: We conducted a comprehensive search for relevant papers in the SCOPUS, PubMed, APA-PsyArticles, Web of Science, Redalyc, and SciELO databases. In the selection process, we specifically focused on studies that included individuals with a confirmed genetic status of HD and investigated ToM functioning in patients with and without motor symptoms. The systematic review followed the PRISMA protocol.

Results: A total of 27 papers were selected for this systematic review, covering the period from 2003 to 2023. The findings consistently indicate that ToM is globally affected in patients with manifest motor symptoms. In individuals without motor symptoms, impairments are focused on the affective dimensions of ToM.

Conclusions: Based on our analysis, affective ToM could be considered a potential biomarker for HD. Therefore, it is recommended that ToM assessment be included as part of neuropsychological evaluation protocols in clinical settings. Suchinclusion could aid in the identification of early stages of the disease and provide new opportunities for treatment, particularly with emerging drugs like antisense oligomers. The Prospero registration number for this review is CRD42020209769.

Background: Huntington's disease (HD) is an autosomal dominant, progressive neurodegenerative disorder debilitating mainly in adults.

Objective: This study aimed to assess the trends in HD-related mortality regarding various demographic factors.

Methods: Death certificates from the CDC WONDER were studied from 1999 to 2019, for HD-related mortality in adults aged 25 + years. Age-adjusted Mortality Rate (AAMR) per 100,000 persons and Annual Percentage Change (APC) were calculated and stratified by year, age groups, gender, race/ethnicity, state, census region, urbanization, and place of death.

Results: Between 1999 to 2019, 22,595 deaths occurred in adults due to HD. The AAMR increased from 0.43 to 0.54 during this period (APC = 0.50; 95% CI: 0.18 to 0.84). Old adults (65-85 + years) had the highest overall AAMR, followed by middle-aged adults (45-64 years) and young adults (25-44 years) (AAMR old: 1.01 vs. AAMR middle-age: 0.68 vs. AAMR young: 0.16). Men had slightly greater overall AAMRs than women (AAMR men: 0.54 vs. AAMR women: 0.48). When stratified by race, non-Hispanic (NH) Whites had significantly higher mortality rates than NH African Americans (AAMR NH White: 0.61 vs. NH African American: 0.35), while the AAMR were lowest in Hispanic/Latino (0.28). The AAMRs also showed variation by region (overall AAMR: Midwest: 0.63, Northeast: 0.47, West: 0.48, South: 0.46), and non-metropolitan areas had higher HD-related AAMR (0.66) than metropolitan areas (0.47).

Conclusions: HD-related mortality in US adults has increased since 1999. Reflecting on the variations in trends observed, new strategies are required to optimize the quality of care in long-term care facilities.

Structural magnetic resonance imaging (MRI) is a powerful tool to visualize 3D neuroanatomy and assess pathology and disease progression in neurodegenerative disorders such as Huntington's disease (HD). The development of mouse models of HD that reproduce many of the psychiatric, motor and cognitive impairments observed in human HD has improved our understanding of the disease and provided opportunities for testing novel therapies. Similar to the clinical scenario, MRI of mouse models of HD demonstrates onset and progression of brain pathology. Here, we provided an overview of the articles that used structural MRI in mouse models of HD to date, highlighting the differences between studies and models and describing gaps in the current state of knowledge and recommendations for future studies.

In this edition of the Huntington's Disease Clinical Trials Update, we expand on the ongoing program from VICO Therapeutics and on the recently terminated VIBRANT-HD clinical trials. We also discuss updates from uniQure's AMT-130 program and PTC therapeutics' trial of PTC518 and list all currently registered and ongoing clinical trials in Huntington's disease.

Somatic instability of the huntingtin (HTT) CAG repeat mutation modifies age-at-onset of Huntington's disease (HD). Understanding the mechanism and pathogenic consequences of instability may reveal therapeutic targets. Using small-pool PCR we analyzed CAG instability in the OVT73 sheep model which expresses a full-length human cDNA HTT transgene. Analyses of five- and ten-year old sheep revealed the transgene (CAG)69 repeat was remarkably stable in liver, striatum, and other brain tissues. As OVT73 sheep at ten years old have minimal cell death and behavioral changes, our findings support instability of the HTT expanded-CAG repeat as being required for the progression of HD.