Brain Advance Access published online on October 25, 2009
Brain, doi:10.1093/brain/awp263
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Cerebrospinal hypocretin, daytime sleepiness and sleep architecture in Parkinson's disease dementia
1 Parkinson disease and Movement Disorders Unit, Neurology Service, Institut Clínic de Neurociències (ICN), Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación en Red de Enfermedades Neurodegenerativas (CIBERNED), Hospital Clínic, c./Villarroel 170, 08036, Barcelona, Catalonia, Spain 2 Multidisciplinary Sleep Disorders Unit and Neurology Service, ICN, IDIBAPS, CIBERNED, Hospital Clínic, Barcelona, Catalonia, Spain 3 Biochemistry and Molecular Genetics Laboratory, Centre de Diagnòstic Biomèdic (CDB), IDIBAPS, Hospital Clínic, Barcelona, Catalonia, Spain 4 Statistics and Methodologic Support Unit, Unitat d’Avaluació, Suport i Prevenció (UASP), Hospital Clínic, IDIBAPS, Barcelona, Catalonia, Spain
Correspondence to:
Maria J. Marti, MD, PhD, Movement Disorders Unit, ICN, IDIBAPS, CIBERNED, Hospital Clínic, c./Villarroel 170, 08036, Barcelona, Spain E-mail: mjmarti{at}clinic.ub.es
Excessive daytime sleepiness is common in Parkinson's disease and has been associated with Parkinson's disease-related dementia. Narcoleptic features have been observed in Parkinson's disease patients with excessive daytime sleepiness and hypocretin cell loss has been found in the hypothalamus of Parkinson's disease patients, in association with advanced disease. However, studies on cerebrospinal fluid levels of hypocretin-1 (orexin A) in Parkinson's disease have been inconclusive. Reports of sleep studies in Parkinson's disease patients with and without excessive daytime sleepiness have also been disparate, pointing towards a variety of causes underlying excessive daytime sleepiness. In this study, we aimed to measure cerebrospinal fluid hypocretin-1 levels in Parkinson's disease patients with and without dementia and to study their relationship to dementia and clinical excessive daytime sleepiness, as well as to describe potentially related sleep architecture changes. Twenty-one Parkinson's disease patients without dementia and 20 Parkinson's disease patients with dementia, along with 22 control subjects without sleep complaints, were included. Both Epworth sleepiness scale, obtained with the help of the caregivers, and mini-mental state examination were recorded. Lumbar cerebrospinal fluid hypocretin-1 levels were measured in all individuals using a radio-immunoassay technique. Additionally, eight Parkinson's disease patients without dementia and seven Parkinson's disease patients with dementia underwent video-polysomnogram and multiple sleep latencies test. Epworth sleepiness scale scores were higher in Parkinson's disease patients without dementia and Parkinson's disease patients with dementia than controls (P < 0.01) and scores >10 were more frequent in Parkinson's disease patients with dementia than in Parkinson's disease patients without dementia (P = 0.04). Cerebrospinal fluid hypocretin-1 levels were similar among groups (controls = 321.15 ± 47.15 pg/ml; without dementia = 300.99 ± 58.68 pg/ml; with dementia = 309.94 ± 65.95 pg/ml; P = 0.67), and unrelated to either epworth sleepiness scale or mini-mental state examination. Dominant occipital frequency awake was slower in Parkinson's disease patients with dementia than Parkinson's disease patients without dementia (P = 0.05). Presence of slow dominant occipital frequency and/or loss of normal non-rapid eye movement sleep architecture was more frequent among Parkinson's disease patients with dementia (P = 0.029). Thus, excessive daytime sleepiness is more frequent in Parkinson's disease patients with dementia than Parkinson's disease patients without dementia, but lumbar cerebrospinal fluid hypocretin-1 levels are normal and unrelated to severity of sleepiness or the cognitive status. Lumbar cerebrospinal fluid does not accurately reflect the hypocretin cell loss known to occur in the hypothalamus of advanced Parkinson's disease. Alternatively, mechanisms other than hypocretin cells dysfunction may be responsible for excessive daytime sleepiness and the sleep architecture alterations seen in these patients.
Key Words: Parkinson's disease; dementia; excessive daytime sleepiness; hypocretin-1; sleep architecture
Abbreviations: EDS, excessive daytime sleepiness; ESS, Epworth sleepiness scale; MMSE, mini-mental state examination; MSLT, multiple sleep latency test; RBD, REM sleep behaviour disorder; REM, rapid eye movement; UPDRS, Unified Parkinson Disease Rating Scale; vPSG, video-polysomnography
Received May 13, 2009. Revised August 25, 2009. Accepted August 27, 2009.