Circadian and sleep disorders in Parkinson's disease

Abstract

Impaired sleep and alertness, initially recognized by James Parkinson in his famous monograph "An Essay on the Shaking Palsy" in 1817, is one of the most common and disabling nonmotor symptoms of Parkinson's disease (PD). It is only recently, however, that sleep disturbances in PD have received the attention of medical and research community. Dopamine, the major neurotransmitter implicated in the pathogenesis of PD, plays a pivotal role in the regulation of sleep and circadian homeostasis. Sleep dysfunction affects up to 90% of patients with PD, and may precede the onset of the disease by decades. Sleep dysfunction in PD may be categorized into disturbances of overnight sleep and daytime alertness. Etiology of impaired sleep and alertness in PD is multifactorial. Co-existent primary sleep disorders, medication side effects, overnight re-emergence of motor symptoms, and primary neurodegeneration itself, are main causes of sleep disruption and excessive daytime sleepiness among patients with PD. Increasing body of evidence suggests that the circadian system becomes dysregulated in PD, which may lead to poor sleep and alertness. Treatment options are limited and frequently associated with unwanted side effects. Further studies that will examine pathophysiology of sleep dysfunction in PD, and focus on novel treatment approaches are therefore very much needed. In this article we review the role of dopamine in regulation of sleep and alertness and discuss main sleep and circadian disturbances associated with PD.

Figure 1

A proposed model for dysregulation of the sleep-wake cycle in PD.