29.: Disturbances in melatonin secretion and circadian sleep-wake regulation in Parkinson’s disease

Abstract

Using salivary dim light melatonin onset (DLMO) and actigraphy, the current study sought to identify whether Parkinson’s disease (PD) patients demonstrate circadian disturbance compared to controls. Additionally, this study investigates whether circadian disturbances represent a disease related process or may be attributed to dopaminergic therapy. Twenty-nine patients with PD were divided into unmedicated and medicated groups and were compared to 27 controls. All participants had neurologic assessment and underwent 14 days of actigraphy to establish habitual sleep onset time (HSO). DLMO time and area under the melatonin curve (AUC) were calculated from salivary melatonin sampling. The phase angle of entrainment was calculated by subtracting DLMO from HSO. Overnight polysomnography was performed to determine sleep architecture. DLMO and HSO were not different across the groups. However, the phase angle of entrainment was more than twice as long in the medicated PD group compared to unmedicated PD (U = 35.5, p = 0.002) and was greater than 50% longer than controls (U = 130.0, p = 0.021). The medicated PD group showed more than double the melatonin AUC compared to the unmedicated group (U = 31, p = 0.001) and controls (U = 87, p = 0.001). There was no difference on these measures comparing unmedicated PD and controls. In PD, dopaminergic treatment profoundly increases the secretion of melatonin. This study reports no difference in circadian phase and HSO between groups. However patients treated with dopaminergic therapy unexpectedly showed a delayed sleep onset relative to DLMO, suggesting dopaminergic therapy in PD results in an uncoupling of circadian and sleep regulation.