Sleep–wake disturbances in common neurodegenerative diseases : a closer look at selected aspects of the neural circuitry

There is a growing appreciation regarding the relationship between common neurodegenerative diseases, such as Alzheimer's and Parkinson's and sleep–wake disturbances. These clinical features often herald the onset of such conditions and certainly appear to influence disease phenotype and progression. This article reviews some of the pathophysiological processes underlying specific disruptions within the neural circuitry underlying sleep–wake disturbances and explores how clinicopathological relationships commonly manifest. It is proposed that a greater understanding of these relationships should allow insights in to the efficacy of currently available treatments and help in the development of future therapies targeting disruptions within the sleep–wake neural circuitry

Schematic diagram showing a typical nocturnal core-body temperature (CBT) profile.

<p>The mesor is defined as the average value around which the CBT fitting oscillates. The nadir is defined as the lowest temperature during sleep. The amplitude is defined as the difference between the mesor and the nadir.</p

Scatter plot demonstrating the strong negative correlation between self-reported symptoms of the nocturnal CBT amplitude and REM Sleep Behaviour Disorder Questionnaire (RBDSQ) score.

<p>Scatter plot demonstrating the strong negative correlation between self-reported symptoms of the nocturnal CBT amplitude and REM Sleep Behaviour Disorder Questionnaire (RBDSQ) score.</p

Disturbances in melatonin secretion and circadian sleep–wake regulation in Parkinson disease

Objective: Using salivary dim light melatonin onset (DLMO) and actigraphy, our study sought to determine if Parkinson disease (PD) patients demonstrate circadian disturbance compared to healthy controls. Additionally, our study investigated if circadian disturbances represent a disease-related process or maybe attributed to dopaminergic therapy. Methods: Twenty-nine patients with PD were divided into unmedicated and medicated groups and were compared to 27 healthy controls. All participants underwent neurologic assessment and 14 days of actigraphyto 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 (PSG) was performed to determine sleep architecture. Results: 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 the unmedicated PD group(U = 35.5; P = .002) and was more than 50% longer than controls (U = 130.0; P = .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 = .001). There was no difference in these measures comparing unmedicated PD and controls. Conclusions: In PD dopaminergic treatment profoundly increases the secretion of melatonin. Our study reported no difference in circadian phase and HSO between groups. However, PD 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