Longitudinal assessment of excessive daytime sleepiness in early Parkinson’s disease

BackgroundExcessive daytime sleepiness (EDS) is common and disabling in Parkinson’s disease (PD). Predictors of EDS are unclear, and data on biological correlates of EDS in PD are limited. We investigated clinical, imaging and biological variables associated with longitudinal changes in sleepiness i...

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Published in:Journal of neurology, neurosurgery and psychiatry Vol. 88; no. 8; pp. 653 - 662
Main Authors: Amara, Amy W, Chahine, Lama M, Caspell-Garcia, Chelsea, Long, Jeffrey D, Coffey, Christopher, Högl, Birgit, Videnovic, Aleksandar, Iranzo, Alex, Mayer, Geert, Foldvary-Schaefer, Nancy, Postuma, Ron, Oertel, Wolfgang, Lasch, Shirley, Marek, Ken, Simuni, Tanya
Format: Journal Article
Language:English
Published: England BMJ Publishing Group LTD 01.08.2017
Subjects:
Adult
Aged
Anxiety
Case-Control Studies
Cross-Sectional Studies
Disorders of Excessive Somnolence - chemically induced
Disorders of Excessive Somnolence - diagnosis
Disorders of Excessive Somnolence - epidemiology
Dopamine
Dopamine Agents - adverse effects
Dopamine Agents - therapeutic use
Dose-Response Relationship, Drug
Female
Humans
Longitudinal Studies
Male
Medical prognosis
Middle Aged
Neurodegeneration
Neurologic Examination - drug effects
Parkinson Disease - diagnosis
Parkinson Disease - drug therapy
Parkinson Disease - epidemiology
Parkinson's disease
Prognosis
Sleep Wake Disorders - diagnosis
Sleep Wake Disorders - drug therapy
Sleep Wake Disorders - epidemiology
Studies
Biomarkers
Excessive daytime sleepiness
Non-motor symptoms
Sleep
Parkinson’s disease
ISSN:0022-3050, 1468-330X, 1468-330X
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Summary:BackgroundExcessive daytime sleepiness (EDS) is common and disabling in Parkinson’s disease (PD). Predictors of EDS are unclear, and data on biological correlates of EDS in PD are limited. We investigated clinical, imaging and biological variables associated with longitudinal changes in sleepiness in early PD.MethodsThe Parkinson’s Progression Markers Initiative is a prospective cohort study evaluating progression markers in participants with PD who are unmedicated at baseline (n=423) and healthy controls (HC; n=196). EDS was measured with the Epworth Sleepiness Scale (ESS). Clinical, biological and imaging variables were assessed for associations with EDS for up to 3 years. A machine learning approach (random survival forests) was used to investigate baseline predictors of incident EDS.ResultsESS increased in PD from baseline to year 3 (mean±SD 5.8±3.5 to 7.55±4.6, p<0.0001), with no change in HC. Longitudinally, EDS in PD was associated with non-tremor dominant phenotype, autonomic dysfunction, depression, anxiety and probable behaviour disorder, but not cognitive dysfunction or motor severity. Dopaminergic therapy was associated with EDS at years 2 and 3, as dose increased. EDS was also associated with presynaptic dopaminergic dysfunction, whereas biofluid markers at year 1 showed no significant associations with EDS. A predictive index for EDS was generated, which included seven baseline characteristics, including non-motor symptoms and cerebrospinal fluid phosphorylated-tau/total-tau ratio.ConclusionsIn early PD, EDS increases significantly over time and is associated with several clinical variables. The influence of dopaminergic therapy on EDS is dose dependent. Further longitudinal analyses will better characterise associations with imaging and biomarkers.
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Contributors AWA: research project: conception and execution; statistical analysis: review and critique; manuscript preparation:writing the first draft, review and critique. LMC: research project:conception; statistical analysis: review and critique; manuscript preparation:drafting/revising manuscript and review and critique. CC-G and JDL: statistical analysis: design, execution and review and critique; manuscript preparation:review and critique. CC: statistical analysis: review and critique; manuscript preparation: review and critique. BH and AV: research project: conception;statistical analysis: review and critique; manuscript preparation: review and critique. AI: research project: organisation; statistical analysis: review and critique; manuscript preparation: review and critique. GM: research project:conception and execution; manuscript preparation: review and critique. NF-S:manuscript preparation: review and critique. RP: statistical analysis: review and critique; manuscript preparation: review and critique. WO: research project: conception and organisation; statistical analysis: review and critique; manuscript preparation: review and critique. SL: research project:conception, organisation and execution; statistical analysis: review and critique; manuscript preparation: review and critique. KM: research project:conception, organisation and execution; statistical analysis: design and review and critique; manuscript preparation: review and critique. TS: research project: conception, organisation and execution; statistical analysis: designand review and critique: manuscript preparation: drafting and review and critique.
ISSN:0022-3050
1468-330X
1468-330X
DOI:10.1136/jnnp-2016-315023