Sleep Disturbances in the Prodromal Stage of Parkinson Disease

Decades of research on neurodegenerative diseases such as Parkinson's disease (PD) have shifted our focus from clinical symptomatic stages to one step earlier, the prodromal stage. There is convincing evidence showing that sleep disorders such as excessive daytime somnolence, insomnia, obstructive sleep apnea, and particularly REM sleep behavior disorder (RBD) are potential prodromal features starting years and decades before conversion to PD. This review aims to provide an overview on various sleep disorders as prodromal features of PD. We start with a discussion of how neuroanatomy of sleep might link to PD pathology. Afterwards, specific sleep disorders that are either known or suspected to be a prodromal symptom for PD, namely insomnia, sleep apnea, somnolence, and RBD, are discussed. Disturbances in serotonergic, cholinergic, dopaminergic, and glutamatergic neurotransmitter systems have made sleep disorders potential candidates for prodromal PD. Nevertheless, the strength of such linkage varies considerably for different entities. While RBD is by far the strongest prodromal manifestation for PD with a high likelihood of phenoconversion and there is reasonable evidence that somnolence can predict PD, data on the prodromal role of sleep apnea and insomnia is limited. Treatment options are available for symptomatic relief of prodromal sleep disorders; however, there is a dearth of knowledge on neuroprotective agents to be used on people with prodromal sleep disorders to either prevent or postpone conversion to PD.