Correlates of excessive daytime sleepiness in de novo Parkinson's disease: A case control study

Parkinson's disease (PD) is a progressive neurodegenerative condition associated with a broad scope of motor and nonmotor symptoms (NMS). Excessive daytime sleepiness (EDS) is one of the most common and debilitating manifestations of NMS in PD. The reported prevalence of EDS in the overall PD population is widely variable (16%-74%) and depends on EDS criteria, disease stage, and ascertainment methods, but it is consistently higher than in the general population.1,2 Respective data on EDS stem largely from studies on patients with advanced PD, whereas hardly any data exist on EDS in early, specifically untreated, PD. The cause of EDS in advanced and treated PD is multifactorial.3 Disease variables that have been reported to be associated with EDS in PD populations include longer disease duration, older age, older age at PD onset, sex, more severe motor manifestations, nontremor dominant motor phenotype, depression, anxiety, cognitive impairment, and hallucinations.4-10 In addition, dopaminergic medications have been shown to have a major negative impact on EDS in PD.4,11-14 The presence of EDS predicts a greater decline over time in motor impairment, cognition, and greater risk of developing dementia.15 Very limited information is available on EDS in early, specifically untreated, PD.16-18 Three small studies assessed EDS in de novo PD patients.16-18 Each of them enrolled fewer than 25 de novo PD patients, and only one had healthy controls (HCs). Excessive daytime sleepiness was defined by Epworth Sleepiness Scale (ESS ≥ 10). All studies came to the same conclusion: that EDS does not seem to be a trait of untreated PD.16-18 More recent studies assessed EDS as part of the overall NMS by using a validated NMS questionnaire.19,20 Prevalence of EDS in the cohort of 97 de novo PD subjects was 3.3% and did not change significantly 2 y later with initiation of dopaminergic therapy (4.4%).20 However, prevalence was substantially higher (28% of 109 subjects) in another de novo cohort compared with 15% of 107 HCs.19 Thus, uncertainty remains regarding the prevalence and clinicobiological correlates of EDS in de novo PD. That is specifically relevant considering that EDS was shown to be one of the risk factors for development of PD in prospective epidemiological studies and may precede onset of motor manifestations of PD,4,21 theoretically corresponding to Braak et al.'s data22 on early involvement of the brainstem sleep wakefulness control system in the disease pathological process.22 We aimed to systematically explore prevalence, clinical, and for the first time biological correlates of EDS in a large group of subjects with early untreated PD compared with HCs.