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ToolsVoysey, Zanna J., Goodman, Anna O. G., Rogers, Lorraine, Holbrook, Jonathan A., Lazar, Alpar S. and Barker, Roger A. (2025) Sleep abnormalities are associated with greater cognitive deficits and disease activity in Huntington’s disease: A 12-year polysomnographic study. Brain Communications, 7 (2). ISSN 2632-1297
Full text not available from this repository. (Request a copy)Abstract
Increasing evidence suggests that the sleep pathology associated with neurodegenerative diseases can in turn exacerbate both the cognitive deficits and underlying pathobiology of these conditions. Treating sleep may therefore bear significant, even disease-modifying, potential for these conditions, but how best and when to do so remains undetermined. Huntington’s disease, by virtue of being an autosomal-dominant neurodegenerative disease presenting in mid-life, presents a key ‘model’ condition through which to advance this field. To date, however, there has been no clinical longitudinal study of sleep abnormalities in Huntington’s disease, and no robust interrogation of their association with disease onset, cognitive deficits and markers of disease activity. Here we present the first such study. Huntington’s disease gene carriers (n=28) and age- and sex-matched controls (n=21) were studied at baseline and 10- and 12-year follow up. All Huntington’s disease gene carriers were premanifest at baseline, and were stratified at follow up into ‘prodromal/manifest’ versus ‘premanifest’ groups. Objective sleep abnormalities were assessed through two-night inpatient polysomnography (PSG) and two-week domiciliary actigraphy, and their association was explored against Montreal Cognitive Assessment, Trail A/B task, Symbol Digit Modalities Task (SDMT), Hopkins Verbal Learning Task (HVLT) and Montgomery-Asberg Depression Rating Scale (MADRS) scores, plus serum neurofilament-light levels. Statistical analysis incorporated cross-sectional ANOVA, longitudinal repeated measures linear models and regressions adjusted for multiple confounders including disease stage. 15 Huntington’s disease gene carriers phenoconverted to prodromal/early manifest Huntington’s disease by study completion. At follow-up, these gene carriers showed more frequent sleep stage changes (p=<0.001, ƞp2=0.62) and higher levels of sleep maintenance insomnia (defined by wake-after-sleep-onset,p=0.002, ƞp2=0.52). The latter finding was corroborated by nocturnal motor activity patterns on follow-up actigraphy (p=0.004, ƞp2=0.32). Greater sleep maintenance insomnia was associated with greater cognitive deficits (Trail A p=<0.001,R²=0.78;SDMT p=0.008,R²=0.63;Trail B p=0.013,R²=0.60) and higher levels of neurofilament-light (p=0.015,R²=0.39). Longitudinal modelling suggested that sleep stage instability accrues from the early premanifest phase, whereas sleep maintenance insomnia emerges closer to phenoconversion. Baseline sleep stage instability was able to discriminate those who phenoconverted within the study period from those who remained premanifest (area under curve=0.81,p=0.024). These results demonstrate that the key sleep abnormalities of premanifest/early Huntington’s disease are sleep stage instability and sleep maintenance insomnia, and suggest that the former bears value in predicting disease onset, while the latter is associated with greater disease activity and cognitive deficits. Intervention studies to interrogate causation within this association could not only benefit patients with Huntington’s disease, but also help provide fundamental proof-of-concept findings for the wider sleep-neurodegeneration field.
| Item Type: | Article |
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| Additional Information: | Data availability statement: The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to their containing information that could compromise the privacy of research participants. Funding information: ZJ Voysey was funded by an Association of British Neurologists/Guarantors of Brain Clinical Research Fellowship (G104701). JA Holbrook was supported by the Centre Parkinson Plus Grant and Cure Parkinson’s Trust. AS Lazar was supported by funding from UK Research and Innovation (ES/W006367/1) and The Wellcome Trust (207799_Z_17_Z). The study was additionally supported by the Cure Huntington’s Disease Initiative Foundation (CHDI‐RG50786), the National Institute for Health Research (BRC‐RG64473) and the National Institute for Health Research Cambridge Biomedical Research Centre (BRC-1215- 20014), the Wellcome Trust (203151/Z/16/Z, 203151/A/16/Z) and the UK Research and Innovation Medical Research Council (MC_PC_17230). The views expressed are those of the authors and not necessarily those of the National Institute of Health Research or the Department of Health and Social Care. |
| Uncontrolled Keywords: | actigraphy,dementia,neurodegeneration,neurofilament light,polysomnography,neurology,psychiatry and mental health,biological psychiatry,cellular and molecular neuroscience ,/dk/atira/pure/subjectarea/asjc/2800/2808 |
| Faculty \ School: | Faculty of Medicine and Health Sciences > School of Health Sciences |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Groups > Dementia & Complexity in Later Life Faculty of Medicine and Health Sciences > Research Centres > Lifespan Health |
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| Depositing User: | LivePure Connector |
| Date Deposited: | 03 Apr 2025 11:30 |
| Last Modified: | 24 Apr 2025 11:30 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/98927 |
| DOI: | 10.1093/braincomms/fcaf126 |
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