Sleep deficits but no metabolic deficits in premanifest Huntington's disease

Lazar, Alpar S, Panin, Francesca, Goodman, Anna O G, Lazic, Stanley E, Lazar, Zsolt I, Mason, Sarah L, Rogers, Lorraine, Murgatroyd, Peter R, Watson, Laura P E, Singh, Priya, Borowsky, Beth, Shneerson, John M and Barker, Roger A (2015) Sleep deficits but no metabolic deficits in premanifest Huntington's disease. Annals of Neurology, 78 (4). pp. 630-648. ISSN 0364-5134

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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. INTERPRETATION: 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.

Item Type: Article
Additional Information: © 2015 The Authors Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Uncontrolled Keywords: adult,asymptomatic diseases,female,humans,huntington disease,male,middle aged,sleep wake disorders
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
Depositing User: Pure Connector
Date Deposited: 07 Dec 2016 00:07
Last Modified: 19 Oct 2023 01:52
DOI: 10.1002/ana.24495


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