RESUMEN
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.
Asunto(s)
Enfermedades Asintomáticas , Enfermedad de Huntington/diagnóstico , Enfermedad de Huntington/metabolismo , Trastornos del Sueño-Vigilia/diagnóstico , Trastornos del Sueño-Vigilia/metabolismo , Adulto , Femenino , Humanos , Enfermedad de Huntington/complicaciones , Masculino , Persona de Mediana Edad , Trastornos del Sueño-Vigilia/etiologíaRESUMEN
Huntington's disease (HD) is a fatal neurodegenerative disease characterized by motor, cognitive, and psychiatric disturbance. In this article, we used polysomnography, actigraphy and a variety of validated questionnaires to ascertain the extent to which sleep changes are identifiable and measurable in mild stage HD, and importantly, to see whether patients are negatively impacted by the changes in their sleep. We found significant differences in sleep architecture and sleep efficiency in patients compared with controls using polysomnography. However, patient scores on the Functional Outcomes of Sleep Questionnaire, Medical Outcomes of Sleep Scale, and Epworth Sleepiness Scale were not significantly different to controls. These results suggest that although marked changes in sleep architecture are present in early HD and can be detected using polysomnography, patients do not necessarily recognize or report these abnormalities.