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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 and Singh, Priya, et al. (2015) In Annals of Neurology 78(4). p.48-630
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... (More)

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.

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publication status
published
keywords
Adult, Asymptomatic Diseases, Female, Humans, Huntington Disease, Male, Middle Aged, Sleep Wake Disorders, Journal Article, Research Support, Non-U.S. Gov't
in
Annals of Neurology
volume
78
issue
4
pages
19 pages
publisher
John Wiley and Sons Inc.
external identifiers
  • scopus:84942370454
ISSN
1531-8249
DOI
10.1002/ana.24495
language
English
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no
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8edb642e-61c1-439b-8f3e-93aa442f3c74
date added to LUP
2016-11-24 14:52:55
date last changed
2017-10-29 04:54:25
@article{8edb642e-61c1-439b-8f3e-93aa442f3c74,
  abstract     = {<p>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.</p><p>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.</p><p>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.</p><p>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.</p>},
  author       = {Lazar, Alpar S and Panin, Francesca and Goodman, Anna O G and Lazic, Stanley E and Lazar, Zsolt I and Mason, Sarah L and Rogers, Lorraine and Murgatroyd, Peter R and Watson, Laura P E and Singh, Priya and Borowsky, Beth and Shneerson, John M and Barker, Roger A},
  issn         = {1531-8249},
  keyword      = {Adult,Asymptomatic Diseases,Female,Humans,Huntington Disease,Male,Middle Aged,Sleep Wake Disorders,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  number       = {4},
  pages        = {48--630},
  publisher    = {John Wiley and Sons Inc.},
  series       = {Annals of Neurology},
  title        = {Sleep deficits but no metabolic deficits in premanifest Huntington's disease},
  url          = {http://dx.doi.org/10.1002/ana.24495},
  volume       = {78},
  year         = {2015},
}