{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T11:09:19Z","timestamp":1791198559326,"version":"4.1.0"},"reference-count":68,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,8,21]],"date-time":"2015-08-21T00:00:00Z","timestamp":1440115200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"crossref","award":["CHDI-RG50786"],"award-info":[{"award-number":["CHDI-RG50786"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"crossref","award":["BRC-RG64473"],"award-info":[{"award-number":["BRC-RG64473"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Medical Research Council program","award":["MC_UP_A090_1005"],"award-info":[{"award-number":["MC_UP_A090_1005"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Huntington disease (HD) is a fatal autosomal dominant, neurodegenerative condition characterized by progressively worsening motor and nonmotor problems including cognitive and neuropsychiatric disturbances, along with sleep abnormalities and weight loss. However, it is not known whether sleep disturbances and metabolic abnormalities underlying the weight loss are present at a premanifest stage.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed a comprehensive sleep and metabolic study in 38 premanifest gene carrier individuals and 36 age\u2010 and sex\u2010matched controls. The study consisted of 2 weeks of actigraphy at home, 2 nights of polysomnography and multiple sleep latency tests in the laboratory, and body composition assessment using dual energy x\u2010ray absorptiometry scanning with energy expenditure measured over 10 days at home by doubly labeled water and for 36 hours in the laboratory by indirect calorimetry along with detailed cognitive and clinical assessments. We performed a principal component analyses across all measures within each studied domain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared to controls, premanifest gene carriers had more disrupted sleep, which was best characterized by a fragmented sleep profile. These abnormalities, as well as a theta power (4\u20137Hz) decrease in rapid eye movement sleep, were associated with disease burden score. Objectively measured sleep problems coincided with the development of cognitive, affective, and subtle motor deficits and were not associated with any metabolic alterations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>The results show that among the earliest abnormalities in premanifest HD is sleep disturbances. This raises questions as to where the pathology in HD begins and also whether it could drive some of the early features and even possibly the pathology. Ann Neurol 2015;78:630\u2013648<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.24495","type":"journal-article","created":{"date-parts":[[2015,7,30]],"date-time":"2015-07-30T01:04:54Z","timestamp":1438218294000},"page":"630-648","source":"Crossref","is-referenced-by-count":122,"title":["Sleep deficits but no metabolic deficits in premanifest <scp>H<\/scp>untington's disease"],"prefix":"10.1002","volume":"78","author":[{"given":"Alpar S.","family":"Lazar","sequence":"first","affiliation":[{"name":"John van Geest Centre for Brain Repair Department of Clinical Neurosciences University of Cambridge Cambridge United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Panin","sequence":"additional","affiliation":[{"name":"John van Geest Centre for Brain Repair Department of Clinical Neurosciences University of Cambridge Cambridge United Kingdom"},{"name":"Faculty of Medical Science Anglia Ruskin University Cambridge United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna O. 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