title: Progressive dopamine and hypocretin deficiencies in Parkinson's disease: is there an impact on sleep and wakefulness?
abstract: Sleep-wake disturbances are frequent in patients with Parkinson's disease, but prospective controlled electrophysiological studies of sleep in those patients are surprisingly sparse, and the pathophysiology of sleep-wake disturbances in Parkinson's disease remains largely elusive. In particular, the impact of impaired dopaminergic and hypocretin (orexin) signalling on sleep and wakefulness in Parkinson's disease is still unknown. We performed a prospective, controlled electrophysiological study in patients with early and advanced Parkinson's disease, e.g. in subjects with presumably different levels of dopamine and hypocretin cell loss. We compared sleep laboratory tests and cerebrospinal fluid levels with hypocretin-deficient patients with narcolepsy with cataplexy, and with matched controls. Nocturnal sleep efficiency was most decreased in advanced Parkinson patients, and still lower in early Parkinson patients than in narcolepsy subjects. Excessive daytime sleepiness was most severe in narcolepsy patients. In Parkinson patients, objective sleepiness correlated with decrease of cerebrospinal fluid hypocretin levels, and repeated hypocretin measurements in two Parkinson patients revealed a decrease of levels over years. This suggests that dopamine and hypocretin deficiency differentially affect sleep and wakefulness in Parkinson's disease. Poorer sleep quality is linked to dopamine deficiency and other disease-related factors. Despite hypocretin cell loss in Parkinson's disease being only partial, disturbed hypocretin signalling is likely to contribute to excessive daytime sleepiness in Parkinson patients.
authors: Department of Neurology, University Hospital, Zurich, Switzerland.
authors: Miriam
authors: M
authors: Wienecke
authors: Esther
authors: E
authors: Werth
authors: Rositsa
authors: R
authors: Poryazova
authors: Heide
authors: H
authors: Baumann-Vogel
authors: Claudio L
authors: CL
authors: Bassetti
authors: Michael
authors: M
authors: Weller
authors: Daniel
authors: D
authors: Waldvogel
authors: Alexander
authors: A
authors: Storch
authors: Christian R
authors: CR
authors: Baumann
mesh_terms: D056044:Actigraphy; D000368:Aged; D000369:Aged, 80 and over; D002385:Cataplexy / Q000134:cerebrospinal fluid / Q000209:etiology / Q000503:physiopathology; D018450:Disease Progression; D004298:Dopamine / Q000134:cerebrospinal fluid / Q000172:deficiency*; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency*; D008297:Male; D008875:Middle Aged; D009290:Narcolepsy / Q000134:cerebrospinal fluid / Q000209:etiology / Q000503:physiopathology*; D009479:Neuropeptides / Q000172:deficiency*; D000068797:Orexins; D010300:Parkinson Disease / Q000134:cerebrospinal fluid / Q000150:complications / Q000503:physiopathology*; D017286:Polysomnography; D011446:Prospective Studies; D012720:Severity of Illness Index; D012893:Sleep Wake Disorders / Q000134:cerebrospinal fluid / Q000209:etiology / Q000503:physiopathology*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D004298:Dopamine