A systematic review of performance-based functional capacity measures for use in Huntington's disease and evaluation of their suitability for clinical trials.Journal of Huntington's disease • April 03, 2025
Tayela Prichard, Cali Roiboit, Meg Rankin, Yifat Glikmann Johnston, Mark Gordon, Julie Stout
BackgroundHuntington's disease (HD) leads to a decline in functional capacity, affecting daily life tasks. Assessing functional capacity in clinical trials is crucial to evaluate treatment effectiveness and substantiate the clinical meaningfulness of more sensitive and reliable measures. Clinician rating scales are commonly used, but performance-based measures of functional capacity may offer advantages, however, there is no consensus on the suitability of existing performance-based measures for use in HD.ObjectiveWe applied a Consensus-based Standards for the selection of health Measurement INstruments (COSMIN) approach to evaluate the potential suitability of performance-based functional capacity measures for HD clinical trials. We also used criteria developed with expert input to assess these measures.MethodsWe conducted a systematic search of relevant databases and screened 1924 articles for inclusion criteria.ResultsWe included a total of 89 articles on 33 performance-based functional capacity measures. Measures were rated from Very Low to Moderate suitability for use in HD clinical trials. DriveSafe DriveAware and EcoKitchen were the only measures tested in HD participants and were rated as having Moderate and Very Low suitability respectively, highlighting the need for further evaluation. Additionally, the Brief University of California San Diego Performance-based Skills Assessment (UCSD UPSA-B) and the Virtual Reality Functional Capacity Assessment Tool (VRFCAT), were identified as potentially useful, also rated Moderate.ConclusionsMultiple performance-based functional capacity measures show potential for use in patients with HD, pending further investigation.
Sleep fragmentation, 24-hr rest-activity patterns, and cognitive function in premanifest Huntington's disease: An actigraphy study.Neuropsychology • March 03, 2025
Emily Fitzgerald, Yifat Glikmann Johnston, Jessica Manousakis, Meg Rankin, Clare Anderson, Melinda Jackson, Julie Stout
Objective: In Huntington's disease (HD), cognitive symptoms, sleep fragmentation, and daily activity pattern alterations can occur up to 15 years before diagnosis in premanifest HD (Pre-HD). Whether sleep and rest-activity patterns relate to cognitive function in Pre-HD, however, remains unclear. We investigated the relationships between rest-activity patterns, sleep, and cognitive function in Pre-HD compared to healthy controls (HCs).
Methods: All participants completed 14 days of actigraphy, online questionnaires, and remote cognitive assessments.
Results: The Pre-HD group (n = 36) performed worse on Speeded Tapping than the HC group (n = 42). Pre-HD participants with heightened sleep fragmentation performed more poorly on the Trail Making Test (TMT) and Hopkins Verbal Learning Test-Revised (HVLT-R). In Pre-HD, lower intra-daily variability and higher interdaily stability (more stable, less fragmented rest-activity patterns) were associated with poorer performance on the trail making test Part B, Symbol Digit Modalities Test, Emotion Recognition Task, Rey Complex Figure Test, visual memory task, paced tapping, and HVLT-R total trial. Higher interdaily stability was also linked to poorer HVLT-R performance. Relative amplitude and sleep regularity index were not related to performance. Poorer sleep quality on the Pittsburgh Sleep Quality Index correlated with worse HVLT-R delayed and paced tapping scores. More severe insomnia (higher Insomnia Severity Index scores) correlated with lower Rey Complex Figure Test copy.
Conclusions: Our findings emphasize the importance of uninterrupted sleep on cognitive function in Pre-HD and reveal targets for interventions aimed at improving cognitive symptoms. Larger cohorts stratified by proximity to diagnosis are critical to improving our understanding of these relationships across the premanifest period. (PsycInfo Database Record (c) 2025 APA, all rights reserved).
Effects and mechanisms of computerized cognitive training in Huntington's disease: protocol for a pilot study.Neurodegenerative Disease Management • January 09, 2025
Katharine Huynh, Sharna Jamadar, Julie Stout, Katharina Voigt, Amit Lampit, Nellie Georgiou Karistianis
Huntington's disease (HD) causes progressive cognitive decline, with no available treatments. Computerized cognitive training (CCT) has shown efficacy in other populations, but its effects in HD are largely unknown. This pilot study will explore the effects and neural mechanisms of CCT in HD. The intervention group participants will complete 12 weeks of multidomain CCT. Control group participants will receive lifestyle education and access to CCT after the study. The primary outcome is change in processing speed. Secondary outcomes include - change in other cognitive domains, functional brain network connectivity (derived from MRI) and psychosocial function. Feasibility outcomes include rates of recruitment, adherence and retention. This study may provide insights into the effects of CCT in HD and guide future trials.Clinical Trial Registration: ACTRN12622000908730 (ClinicalTrials.gov).
Using cluster analysis to identify the health literacy strengths and challenges of people living with motor neurone disease in Australia.BMC Health Services Research • December 11, 2024
Arabelle Douglas, Maryanne Mcphee, Fiona Fisher, Christina Cheng, Anjali Henders, Laura Ziser, Julie Stout, Matthew Kiernan, Richard Osborne, Susan Mathers
Background: There is growing appreciation of the role health literacy plays in population health and health care design. Health literacy encompasses an individual's capacity to manage their health and the responsiveness of the health system. Our aim was to identify the health literacy strengths and challenges in an Australian cohort living with motor neurone disease (MND), including both people living with the disease and their carers.
Methods: This study used the Health Literacy Questionnaire and eHealth Literacy Questionnaire for health literacy assessment. Using a secure online platform, an anonymous survey was disseminated which included demographic data and clinical measurements. Descriptive statistical analysis and cluster analysis were employed to describe the sample and to identify different health literacy patterns in subgroups of people living with MND and their carers.
Results: A total of 227 people participated (171 people living with MND and 56 carers). Cluster analysis generated fifteen cluster profiles for the cohort living with MND and seven cluster profiles for carers. The variability and potential significance of patterns of health literacy strengths and challenges within the MND community are described. There was extensive diversity within the sampled population, with a mix of sociodemographic backgrounds across each cluster profile.
Conclusions: The health literacy cluster profiles created from this study provide insight into the full spectrum of where the challenges and strengths exist for individuals and subgroups of people managing this fatal disease. The results from this study pave the way for generating system wide interventions that address health literacy diversity, to create more enabling health care environments for all those affected by MND.
Neural Mechanisms of Object Location Memory in Huntington's Disease.Movement Disorders : Official Journal Of The Movement Disorder Society • December 06, 2024
Yifat Glikmann Johnston, Garance Delagneau, Tamrin Barta, Julie Stout, Adeel Razi
Background: Object-location memory impairment in Huntington's disease (HD) occurs from premanifest period and declines as HD progresses, however, pathogenesis of object-location memory is unknown. The striatum and hippocampus are affected in HD, functionally interacting allowing intact object-location memory.
Objective: The present study investigated if object location memory impairment in premanifest and manifest HD was associated with aberrations in effective connectivity between striatum and hippocampal formation.
Methods: Using dynamic causal modelling, we examined effective connectivity between the striatum and hippocampus and association with object-location memory in 35 HD participants (23 premanifest, 12 early manifest) and 32 controls.
Results: HD participants' object-location memory was worse than controls, with performance associated with aberrant effective connectivity from the striatum to hippocampal formation, lower connectivity was associated with poorer object-location memory. Connectivity from hippocampal formation to the striatum was lower in manifest HD. In premanifest HD, connectivity from parahippocampal gyrus to the striatum was stronger and associated with better object-location memory.
Conclusions: Findings raise questions regarding compensatory neural processes in HD and other neurodegenerative diseases, providing pathophysiological evidence that cognitive impairment may be related to connectopathy. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
