Excessive daytime sleepiness in Parkinson disease: is it the drugs or the disease?
Gjerstad MD, Alves G, Wentzel-Larsen T, Aarsland D, Larsen JP;
Commented by , 26 Oct 2006
Background
Patients with Parkinson disease (PD) have a tendency to sleep more during daytime, sometimes even under inappropriate conditions, such as on the steering wheel as they drive a car. Some of these excessive daytime sleepiness and sleeep attacks have been blamed on drugs, especially on dopaminergic agonists, whereas others put the blame on the disease process itself. Researchers from Norway, who have substantially contributed to the field before, decided to have a closer look.
Objectives
The objective of this study was to examine the associated demographic faetures, clinical correlates and the development of excessive daytime seleepiness (EDS) over an 8 year period in a community-based cohort of patients with PD.
Methods
A total of 232 patients with PD were included in a population-based prevalence study in 1993. Patients were followed prospectively and re-examined after 4 and 8 years. At all study visits, semistructured interviews were administered in order to obtain information on clinical and demographic variables. Standardized rating scales were used to assess parkinsonism, depression and cognitive impairment.
The diagnosis of EDS was based on a sleep questionnaire and as of 2001 also on the Epworth Sleepines Scale. Population-averaged logistic regression models for correleated data were performed to assess the relationship between EDS and various demographic and clinical variables.
Results
From the original cohort of the 232 patients assessed at baseline 138 were available for re-evaluation after 4 years and 89 patients after 8 years. Frequency of EDS increased from 5.6% in 1993 to 22.5% in 1997 and 40.8 in 2001, with an 8-year prevalence of 54.2%. In the majortiy of patients EDS was a persistent feature. In the logistic regression model, EDS was related to age, gender, and use of dopaminergic agonists.
In those who never used dopamine agonists hypersomnia was associated with the Hoehn and Yahr stage only. The authors conluded that EDS is a frequent and persistent feature in PD with multifactorial underlying pathophysiology:
- the findings indicate that both age and disease related disturbances of sleep-wake regulation as well as treatment with dopamine agonists contribute to hypersomnia in PD.
Professor Emre's comments
The truth is often not one-sided. This seems also to be the case with regard to the underlying pathophysiology of EDS in patients with PD, as revealed in this study. The logistic regression analysis demonstrated that age, use of dopamine agonists and disease severity were associated with development of EDS in PD patients. This is a clear indication that aging process, disease pathology and drugs, i.e. dopaminergic agonists contribute to the development of this problem.
The role of dopamine agonists is possibly limited as a substantial number of patients who never used these drugs also experienced EDS. That, once developed, EDS was persistent in the vast majority of patients also underscores the role of mechanistic factors, i.e. the contribution of the disease pathology, as symptoms caused by changes in the anatomo-physiology of the brain tend to be persistent.
Excessive daytime sleepiness or hypersomnia in patients with PD has been reported with variable rates in cross-sectional, clinic-based studies (ref. 1, ref. 2), not surprisingly so as they evaluated patients with different disease severity and age range.
The same group of researchers involved in this study, had found in a cross-sectional survey that severe somnolence was much more frequent in patients with PD (15%) as compared to age matched controls (1%) (ref. 3). Their 4-year results in the same cohort of patients followed in this study had already revaled that the frequency of EDS increased from baseline values of 8% to 29% at 4 years (ref. 4).
The 8 year results showed that the rates further increased in the course of the disease. This study is more powerful than the previous cross-sectional reports as it is a prospective observation of a population-based cohort for a considerable time period. One weakness is that almost two-thirds of the patients were lost to follow-up, one wonders if these patients represented a healthier or a more sick population, either way may have introduced a bias.
This aspect, however, does not lessen the value of this study, which clearly demontrates that excessive daytime sleepiness becomes a significant and frequent problem as PD progresses, and sheds light on the processes involved.
References
1. Ondo WG, Dat Vuong K, Khan H, Atassi F, Kwak C, Jankovic J. Daytime sleepiness and other sleep disorders in Parkinson's disease. Neurology 2001; 57 (8); 1392-1396
2. Brodsky MA, Godbold J, Roth T, Olanow CW. Sleepiness in Parkinson's disease: a controlled study. Movement Disorders 2003; 18 (6); 668-672
3. Tandberg E, Larsen JP, Karlsen K. Excessive daytime sleepiness and sleep benefit in Parkinson's disease: a community-based study. Movement Disorders 1999; 14 (6); 922-927
4. Gjerstad MD, Aarsland D, Larsen JP. Development of daytime somnolence over time in Parkinson's disease. Neurology 2002; 58 (10); 1544-1546