title: Sleep deficits but no metabolic deficits in premanifest Huntington's disease.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  We performed a comprehensive sleep and metabolic study in 38 premanifest gene carrier individuals and 36 age- and sex-matched 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-ray 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.
  
  
  RESULTS
  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 (4-7Hz) 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Alpar S
authors.initials: AS
authors.lastname: Lazar
authors.affiliation: John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.|Faculty of Medical Science, Anglia Ruskin University, Cambridge, United Kingdom.
authors.forename: Francesca
authors.initials: F
authors.lastname: Panin
authors.affiliation: John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Anna O G
authors.initials: AO
authors.lastname: Goodman
authors.affiliation: In Silico Lead Discovery, Novartis Institutes for Biomedical Research, Basel, Switzerland.
authors.forename: Stanley E
authors.initials: SE
authors.lastname: Lazic
authors.affiliation: Department of Physics, Babes-Bolyai University, Cluj-Napoca, Romania.
authors.forename: Zsolt I
authors.initials: ZI
authors.lastname: Lazar
authors.affiliation: John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Mason
authors.affiliation: Respiratory Support and Sleep Centre, Papworth Hospital, Cambridge, United Kingdom.
authors.forename: Lorraine
authors.initials: L
authors.lastname: Rogers
authors.affiliation: National Institute for Health Research/Wellcome Trust Clinical Research Facility, Addenbrooke's Hospital, Cambridge, United Kingdom.|University of Cambridge Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, Addenbrookes Hospital, Cambridge, United Kingdom.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Murgatroyd
authors.affiliation: National Institute for Health Research/Wellcome Trust Clinical Research Facility, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors.forename: Laura P E
authors.initials: LP
authors.lastname: Watson
authors.affiliation: Medical Research Council Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge, United Kingdom.
authors.forename: Priya
authors.initials: P
authors.lastname: Singh
authors.affiliation: CHDI Management/CHDI Foundation, Princeton, NJ, United States of America.
authors.forename: Beth
authors.initials: B
authors.lastname: Borowsky
authors.affiliation: Respiratory Support and Sleep Centre, Papworth Hospital, Cambridge, United Kingdom.
authors.forename: John M
authors.initials: JM
authors.lastname: Shneerson
authors.affiliation: John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Roger A
authors.initials: RA
authors.lastname: Barker
mesh_terms: D000328:Adult; D058070:Asymptomatic Diseases; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000150:complications / Q000175:diagnosis* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012893:Sleep Wake Disorders / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism*