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Background: In biomedicine, machine learning (ML) has proven beneficial for the prognosis and diagnosis of different diseases, including cancer and neurodegenerative disorders. For rare diseases, however, the requirement for large datasets often prevents this approach. Huntington's disease (HD) is a rare neurodegenerative disorder caused by a CAG repeat expansion in the coding region of the huntingtin gene. The world's largest observational study for HD, Enroll-HD, describes over 21,000 participants. As such, Enroll-HD is amenable to ML methods. In this study, we pre-processed and imputed Enroll-HD with ML methods to maximise the inclusion of participants and variables. With this dataset we developed models to improve the prediction of the age at onset (AAO) and compared it to the well-established Langbehn formula. In addition, we used recurrent neural networks (RNNs) to demonstrate the utility of ML methods for longitudinal datasets, assessing driving capabilities by learning from previous participant assessments., Results: Simple pre-processing imputed around 42% of missing values in Enroll-HD. Also, 167 variables were retained as a result of imputing with ML. We found that multiple ML models were able to outperform the Langbehn formula. The best ML model (light gradient boosting machine) improved the prognosis of AAO compared to the Langbehn formula by 9.2%, based on root mean squared error in the test set. In addition, our ML model provides more accurate prognosis for a wider CAG repeat range compared to the Langbehn formula. Driving capability was predicted with an accuracy of 85.2%. The resulting pre-processing workflow and code to train the ML models are available to be used for related HD predictions at: https://github.com/JasperO98/hdml/tree/main ., Conclusions: Our pre-processing workflow made it possible to resolve the missing values and include most participants and variables in Enroll-HD. We show the added value of a ML approach, which improved AAO predictions and allowed for the development of an advisory model that can assist clinicians and participants in estimating future driving capability., (© 2023. The Author(s).)

Huntington's disease (HD) is an inherited neurodegenerative disease. People at risk for HD can choose to get predictive testing years before the clinical onset. HD is characterized by motor, cognitive and psychiatric symptoms and has a mean age at onset between 30 and 50 years, an age at which people are usually still working. This systematic review focuses on summarizing which disease-specific characteristics influence employment and working capacity in HD. Twenty-three studies were identified and showed that while employment and working capacity in HD are negatively influenced by cognitive decline and motor impairments, apathy already plays a role in the prodromal stage. Moreover, the influence of HD transcends the clinical manifestation of the disease, as some people at risk are already experiencing the impact of HD on employment through fear of or actual genetic discrimination. Employment and working capacity are not influenced by predictive testing for HD in and of itself., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Huntington's disease (HD) is an inherited neurodegenerative disorder that is characterized by motor, cognitive, and psychiatric symptoms. Although 65%of HD expanded gene carriers report changes in employment as the first functional loss, little is known about the predictors leading to changes of working capacity. Given the impact on quality of life, understanding of these factors is of great clinical value., Objective: This study evaluates disease specific characteristics and their predictive value in loss of working capacity in HD., Methods: Longitudinal data was collected through the worldwide observational study (Enroll-HD), with 15,301 participants in total and 2,791 HD and healthy control participants meeting the inclusion criteria. Changes in working capacity were analyzed by means of a survival analysis. Predictive values of demographic factors and clinical characteristics were assessed for premanifest and manifest HD through Cox regressions., Results: HD expanded gene carriers, manifest and premanifest combined, had a 31%chance of experiencing changes in employment after three years, compared to 4%in healthy controls. Apathy was found to be the most crucial determinant of working capacity changes in premanifest HD, while executive and motor dysfunction play an important role in manifest HD., Conclusion: HD expanded gene carriers are more likely to lose working capacity compared to healthy controls. Disease progression, altered motor function, cognitive decline, and in an early stage of the disease apathetic symptoms are indicative of negative changes in working capacity. Clinicians should recognize that early disease related changes, especially apathy, can affect working capacity.

Objective: In Huntington's disease (HD), a hereditary neurodegenerative disorder, cognitive impairment in early disease stages mainly involves executive dysfunction. However, visual cognitive deficits have additionally been reported and are of clinical relevance given their influence on daily life and overall cognitive performance. This study aimed to assess visual perceptual skills in HD gene carriers., Methods: Subtasks of the Visual Object and Space Perception battery and Groningen Intelligence Test were administered in 62 participants (18 healthy controls, 22 participants with a genetic confirmation of HD without symptoms, i.e., premanifest HD, and 22 participants with a genetic confirmation of HD with symptoms, i.e., manifest HD). Group differences in task performance were measured using analysis of covariance with and without correction for age. Receiver Operating Characteristics (ROC) analysis was performed to examine which task best discriminated between groups and cut-off scores were provided., Results: Manifest HD performed significantly worse compared to both controls and premanifest HD on all visual perceptional tasks. Premanifest HD did not differ in task performance from controls. Besides the Shape Detection, all tasks were robust in discriminating between groups. The Animal Silhouettes test was most accurate in discriminating manifest HD from premanifest HD (AUC = 0.90, SE = 0.048, p < .001)., Conclusion: Visual perceptual deficits are present in early manifest HD, especially an impaired recognition of animals and objects from sketched silhouettes, and not in premanifest HD. This suggests that decline in visual processing only occurs in clinical disease stages. The visual cognitive battery, especially the Silhouettes tasks used in this study is sensitive in discriminating manifest HD from premanifest HD and controls., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

It is remarkable that studies focusing on the prevalence and the burden of pain in patients with Huntington disease (HD) are scarce. This may lead to inadequate recognition of pain and hence lack of treatment, eventually affecting the quality of life. The aim of this review is to investigate the prevalence of pain and its burden in HD by performing a systematic literature search. In February 2018, a systematic search was performed in the electronic databases of Pubmed, Embase, Cinahl, Cochrane, and PsycINFO. Studies focusing on patients with juvenile HD were excluded. All other types of study were included without language restrictions. In total, 2234 articles were identified, 15 of which met the inclusion criteria and provided information on 2578 patients with HD. The sample-weighted prevalence of pain was 41.3% (95% confidence interval: 36%-46%). The pain burden, which was measured with the SF-36, is significantly less compared with that in the general population. The sample-weighted mean score on the SF-36 was 84 (95% confidence interval: 81-86), where a score of 100 represents the lowest symptom burden. The results demonstrate that pain could be an important nonmotor symptom in patients with HD, and there are indications that the pain burden could be diminished because of HD. Larger and high-quality prospective cohort and clinical studies are required to confirm these findings. In the meantime, awareness about pain and its burden in patients with HD is warranted in clinical practice.

In most Huntington's disease expanded gene carriers (HDEGC), losing work capacity is the first sign of functional decline. Cognitive deterioration, motor dysfunction, and psychiatric disturbances are associated with or predict work outcomes in HD. The role of profession-specific requirements, however, has not been investigated.This study examines the relationship between work outcomes, clinical characteristics, burnout, and profession-specific requirements in HDEGC. We hypothesize that burnout-like symptoms are associated with mild apathy and that profession-specific requirements influence clinical characteristics affecting work capacity in HD.A cohort of 117 HDEGC (CAG repeat ≥36) participated in the “HD-work” study at Leiden University Medical Center. Participants were 18–67 years old, either, worked at baseline, or had lost their job within two years. The Unified Huntington's Disease Rating Scale assessed motor abilities, global functioning, and cognition. The HD-work questionnaire and the ‘Utrecht Burn Out Scale’ assessed work problems and burnout. Statistical methods included descriptive statistics, Pearson correlations, Cronbachs alpha, t-tests, and logistic regressions.Burnout-like symptoms did not differ between those with full and reduced working capacity and were not more prevalent in HD than in the general Dutch population. No significant effect was found between work outcomes and profession-specific requirements, even when adjusted for clinical characteristics.Our study suggests that profession-specific requirements do not significantly impact work ability among individuals with HD in early phases of HD. Workplace adjustments should be tailored to individual preferences rather than profession-specific demands. Burnout-like symptoms did not affect work capacity or relate to apathy. [ABSTRACT FROM AUTHOR]

Highlights • Older age and female gender are associated with symptoms of simulator sickness. • Huntington's disease does not increase the risk of developing simulator sickness. • Decreased smooth ocular pursuit is a predictor of dropout due to simulator sickness. • Cognitive functioning is unrelated to simulator sickness. Abstract Objective Investigating driving competence with a simulator provides a controlled setting and has a high reproducibility. In addition, there is less risk of physical harm compared to on-road tests. A disadvantage of using simulators is the occurrence of simulator sickness, which is comparable to symptoms of motion sickness. The aim of this study was to examine whether patients with Huntington's disease (HD) are more susceptible to develop simulator sickness compared to healthy individuals. Further, we investigated if the clinical symptoms of HD, such as motor disabilities and cognitive deterioration, might increase the occurrence of simulator sickness. Methods Eighty-three participants (54 HD, 29 controls) drove in a driving simulator that included urban and motorway scenarios. All participants were still active drivers. Motor, cognitive, and oculomotor assessments were administered. Participants completed a questionnaire after the driving session to report possible symptoms of simulator sickness. Results Fifty-eight (70%) participants completed the driving session, while 25 (30%) participants dropped out due to simulator sickness. The most reported symptoms of simulator sickness by dropouts were difficulties concentrating, dizziness, nausea, sweating, and vomiting. Dropouts were significantly older and more often female compared to completers. Decreased smooth ocular pursuit was predictive of dropout due to simulator sickness. The number of HD participants and controls in the dropout group was comparable. There was no significant difference in cognitive performance and motor functioning between completers and dropouts. Conclusions HD participants did not have a higher chance of developing simulator sickness while driving in a simulator compared to controls. Female gender, older age, and smooth ocular pursuit were associated with increased simulator sickness, whereas cognitive and motor functioning were unrelated to dropout due to simulator sickness. [ABSTRACT FROM AUTHOR]