Course and risk factors for excessive daytime sleepiness in Parkinson's disease

https://doi.org/10.1016/j.parkreldis.2016.01.020Get rights and content

Highlights

  • EDS is a non-persistent symptom in patients with Parkinson's disease.

  • With longer disease duration, a large proportion of PD patients develops EDS.

  • A higher dopamine agonist dose is associated with higher EDS scores at follow-up.

  • The use of antihypertensives is associated with higher EDS scores during follow-up.

  • Patients with the PIGD phenotype are at increased risk of developing EDS.

Abstract

Introduction

Excessive daytime sleepiness (EDS) is a common feature of Parkinson's disease (PD) that contributes to the disease burden and increases risk of harm. The aim of this study was to examine persistency, cross-sectional and longitudinal associations, and risk factors for EDS in patients with PD.

Methods

Analyses were performed on data from the SCOPA–PROPARK cohort, a 5-year hospital-based longitudinal cohort of over 400 PD patients who were examined annually. Cross-sectional analyses were conducted to evaluate differences between patients with and without EDS at baseline, while linear mixed models using data of all patients were used to identify factors associated with longitudinal changes in SCOPA-SLEEP-Daytime Sleepiness (SCOPA-SLEEP-DS) scores. A survival analysis was done using data of patients without EDS at baseline to identify risk factors for future EDS.

Results

EDS proved a non-persistent symptom, although persistency and the proportion of patients with EDS increased with longer follow-up. At baseline 43% of patients had EDS, while 46% of patients without EDS at baseline developed this symptom during follow-up. Male gender, poorer nighttime sleep, cognitive and autonomic dysfunction, hallucinations, less severe dyskinesias, dose of dopamine agonists and use of antihypertensives were associated with higher EDS scores over time, while use of benzodiazepines was associated with lower scores. Baseline SCOPA-SLEEP-DS score and PIGD phenotype were risk factors for future EDS.

Conclusion

With longer disease duration a large proportion of patients develop EDS. Some risk factors are modifiable and patients should be monitored to improve quality of life and reduce risk of harm.

Introduction

Excessive daytime sleepiness (EDS) is a common feature of Parkinson's disease (PD), which can affect up to 50% of patients [1]. The American Academy of Sleep Medicine defines EDS as the inability to maintain wakefulness and alertness during the major waking episodes of the day, with sleep occurring unintentionally or at inappropriate times almost daily for at least three months [2].

EDS in PD contributes significantly to the disease burden, and increases the risk of harm to patients [3]. Understanding the risk factors for EDS may help to prevent, identify, and target interventions to the correct patients.

Earlier studies found that the presence of EDS is associated with dopamine agonist (DA) use, higher age, male gender, advanced disease, the postural-instability-gait-difficulty (PIGD) motor phenotype, insomnia, hallucinations, cognitive decline and depression [4], [5]. Information on the relation between EDS and the use of medications such as antidepressants, antihypertensives and benzodiazepines, which are known to cause sleepiness in the general population, is scarce in PD [6], [7].

The results on associated variables and predictors for EDS from previous studies were often inconsistent, likely due to small sample sizes and methodological differences between these studies [4], [5].

Furthermore, most previous studies on EDS in PD had a cross-sectional design and to date only two longitudinal studies have been performed [4], [5]. One study (n = 131) showed that 23% of patients who were free of EDS developed this feature during a four-year follow-up period and that the presence of EDS was associated with more severe disability and cognitive impairment. Although this study had a longitudinal setup, data of patients with EDS at baseline were pooled with those who developed EDS during follow-up, after which they were compared to those of patients who had no EDS at both time points. This strategy therefore actually involved a cross-sectional comparison and the data provide limited information on features that are related to changes in EDS over time [5].

The other study (n = 153) – performed in early, initially drug-naïve patients – found that the occurrence of EDS increases with disease progression and that its presence is not a persistent feature but instead may fluctuate over time; they further found that EDS severity is associated with male gender, depression, ADL disability and DA use [4].

Large longitudinal studies on EDS in more advanced PD are lacking. The PROPARK cohort study includes over 400 PD patients who have been examined annually and followed for five years (i.e., six assessments), which makes this study very well-suited for the purpose of identifying factors associated with (the development of) EDS in PD.

Section snippets

The PROPARK cohort

Patients were recruited from neurology clinics of university and regional hospitals in the western part of the Netherlands and all fulfilled the United Kingdom Parkinson's disease Society Brain Bank criteria for idiopathic PD [8]. The majority of patients were evaluated at the Leiden University Medical Center, but more severely affected patients were offered the possibility to be examined at their homes to prevent selective drop-out. In view of the fact we aimed to obtain information on the

Results

Of the 413 patients of whom an EDS score was available at baseline, 179 (43%) were classified as having EDS and 234 patients were classified as not having EDS (see for details Fig. 1). Of the 234 patients without EDS at baseline, 108 patients (46%) developed this symptom during the follow-up period.

During the 5-year follow-up period (Fig. 1), EDS proved a non-persistent symptom, although the proportion of patients with EDS increased over time. In addition, with longer follow-up and disease

Discussion

We examined persistency, cross-sectional and longitudinal associations, and risk factors for EDS in a cohort of over 400 patients with PD who have been followed for up to five years. The analysis showed that EDS is not a stable feature but that its presence fluctuates. With longer follow-up, however, the proportion of patients with EDS increases and the feature becomes more persistent, indicating the relevance of evaluating its presence, particularly in patients who are at risk. We found that

Relevant conflicts of interest/financial disclosures

Nothing to report.

Acknowledgements

The work reported in this article was supported by grants from the Van Alkemade-Keuls Foundation and the Prinses Beatrix Fonds (grant no. WAR05–0120).

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