{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T06:20:58Z","timestamp":1788330058175,"version":"build-2803163510"},"reference-count":84,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T00:00:00Z","timestamp":1743552000000},"content-version":"vor","delay-in-days":91,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"British Neurologists"},{"name":"Guarantors of Brain Clinical Research","award":["G104701"],"award-info":[{"award-number":["G104701"]}]},{"DOI":"10.13039\/501100019544","name":"Cambridge Centre for Parkinson-Plus","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100019544","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008487","name":"Cure Parkinson's Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008487","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014013","name":"UK Research and Innovation","doi-asserted-by":"publisher","award":["ES\/W006367\/1"],"award-info":[{"award-number":["ES\/W006367\/1"]}],"id":[{"id":"10.13039\/100014013","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["207799_Z_17_Z"],"award-info":[{"award-number":["207799_Z_17_Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["203151\/Z\/16\/Z"],"award-info":[{"award-number":["203151\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["203151\/A\/16\/Z"],"award-info":[{"award-number":["203151\/A\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006500","name":"Cure Huntington's Disease Initiative","doi-asserted-by":"publisher","award":["CHDI-RG50786"],"award-info":[{"award-number":["CHDI-RG50786"]}],"id":[{"id":"10.13039\/100006500","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","award":["BRC-RG64473"],"award-info":[{"award-number":["BRC-RG64473"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018956","name":"National Institute for Health Research Cambridge Biomedical Research Centre","doi-asserted-by":"publisher","award":["BRC-1215\u201320014"],"award-info":[{"award-number":["BRC-1215\u201320014"]}],"id":[{"id":"10.13039\/501100018956","id-type":"DOI","asserted-by":"publisher"}]},{"name":"UK Research and Innovation Medical Research Council","award":["MC_PC_17230"],"award-info":[{"award-number":["MC_PC_17230"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>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 \u2018model\u2019 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 \u2018prodromal\/manifest\u2019 versus \u2018premanifest\u2019 groups. Objective sleep abnormalities were assessed through two-night inpatient polysomnography and 2-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\u2013Asberg 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. Fifteen 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 \u2264 0.001, \u03b7p2 = 0.62) and higher levels of sleep maintenance insomnia (defined by wake after sleep onset, P = 0.002, \u03b7p2 = 0.52). The latter finding was corroborated by nocturnal motor activity patterns on follow-up actigraphy (P = 0.004, \u03b7p2 = 0.32). Greater sleep maintenance insomnia was associated with greater cognitive deficits (Trail A P \u2264 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\u2013neurodegeneration field.<\/jats:p>","DOI":"10.1093\/braincomms\/fcaf126","type":"journal-article","created":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T21:38:24Z","timestamp":1743370704000},"source":"Crossref","is-referenced-by-count":7,"title":["Sleep abnormalities are associated with greater cognitive deficits and disease activity in Huntington's disease: a 12-year polysomnographic study"],"prefix":"10.1093","volume":"7","author":[{"given":"Zanna J","family":"Voysey","sequence":"first","affiliation":[{"name":"Department of Clinical Neurosciences, John van Geest Centre for Brain Repair, University of Cambridge , Cambridge CB2 0PY ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna O G","family":"Goodman","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, John van Geest Centre for Brain Repair, University of Cambridge , Cambridge CB2 0PY ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorraine","family":"Rogers","sequence":"additional","affiliation":[{"name":"Royal Papworth Hospital Foundation Trust, Sleep Centre , Cambridge CB2 0AY ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan A","family":"Holbrook","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, John van Geest Centre for Brain Repair, University of Cambridge , Cambridge CB2 0PY ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alpar S","family":"Lazar","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Sciences, University of East Anglia , Norwich NR4 7TQ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger A","family":"Barker","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, John van Geest Centre for Brain Repair, University of Cambridge , Cambridge CB2 0PY ,","place":["UK"]},{"name":"Cambridge Stem Cell Institute, University of Cambridge , Cambridge CB2 0AW ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,4,2]]},"reference":[{"issue":"1","key":"2025041209271385900_fcaf126-B1","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1159\/000335363","article-title":"Prevalence of sleep disturbances in mild cognitive impairment and dementing disorders: A multicenter Italian clinical cross-sectional study on 431 patients","volume":"33","author":"Guarnieri","year":"2012","journal-title":"Dement Geriatr Cogn Disord"},{"key":"2025041209271385900_fcaf126-B2","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.smrv.2016.08.001","article-title":"A systematic review of the literature on disorders of sleep and wakefulness in Parkinson\u2019s disease from 2005 to 2015","volume":"35","author":"Chahine","year":"2017","journal-title":"Sleep Med Rev"},{"key":"2025041209271385900_fcaf126-B3","doi-asserted-by":"crossref","first-page":"105031","DOI":"10.1016\/j.nbd.2020.105031","article-title":"It\u2019s complicated: The relationship between sleep and Alzheimer\u2019s disease in humans","volume":"144","author":"Lucey","year":"2020","journal-title":"Neurobiol Dis"},{"issue":"1","key":"2025041209271385900_fcaf126-B4","first-page":"e12303","article-title":"Night-to-night variation in sleep associates with day-to-day variation in vigilance, cognition, memory, and behavioral problems in Alzheimer?s disease. Alzheimer\u2019s Dement Diagnosis","volume":"14","author":"Balouch","year":"2022","journal-title":"Assess Dis Monit"},{"issue":"6315","key":"2025041209271385900_fcaf126-B5","first-page":"1004","article-title":"Mechanisms linking circadian clocks, sleep, and neurodegeneration","volume":"354","author":"Musiek","year":"2016","journal-title":"Science (1979)."},{"issue":"2","key":"2025041209271385900_fcaf126-B6","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1002\/acp.3463","article-title":"Effects of sleep deprivation on executive functioning, cognitive abilities, metacognitive confidence, and decision making","volume":"33","author":"Aidman","year":"2019","journal-title":"Appl Cogn Psychol"},{"issue":"5","key":"2025041209271385900_fcaf126-B7","first-page":"553","article-title":"Sleep deprivation: Impact on cognitive performance","volume":"3","author":"Alhola","year":"2007","journal-title":"Neuropsychiatr Dis 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