Sleep disorder in PD: a role for circadian rhythm disturbance?

 

Sleep disorders are a non-motor symptom reported to occur in most PD patients at some stage of the disease. In newly-diagnosed PD, sleep disturbances appear to be uncommon although subjects may reported daytime naps and dream-related behaviours (Prudon et al. Mov Disord 2014;29:259-263).

Later in the disease course, sleep disorders may be due to neurodegenerative changes or secondary to drug treatment. Associated disorders may include restless legs syndrome, REM sleep behaviour disorder, and obstructive sleep apnea (Schulte & Winkelmann. J Neurol 2011;258(suppl 2):S328-335).

A recent meta-analysis of modafinil found that there was insufficient evidence for recommending the drug for PD patients with excessive daytime sleepiness (Sheng et al. PLoS One 2013;8:e81802; free full text at www.ncbi.nlm.nih.gov/pmc/articles/PMC3849275/pdf/pone.0081802.pdf).

A novel suggestion is that disturbances to circadian rhythm may play a role in sleep-wake disturbances in PD. To investigate this, a cross-sectional study monitored serum melatonin levels in 20 PD patients on stable dopaminergic therapy and 15 age-matched controls (Videnovic et al. JAMA Neurol 2014; epublished February 24, 2014). Melatonin levels were determined every 30 minutes over a 24-hour period. Self-reported sleep values were assessed according to the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale.

PD patients demonstrated a blunted circadian rhythm of melatonin secretion compared to controls. Both the amplitude of the melatonin rhythm and the 24-hour area-under-the-curve (AUC) were significantly lower in PD subjects versus controls. Patients with excessive daytime sleepiness (ESS score >10) had a significantly lower amplitude of melatonin rhythm and 24-hour melatonin AUC.

Melatonin circadian rhythm was not related to levodopa-equivalent dose or UPDRS scores. The authors suggested that interventions that target circadian rhythm, such as timed bright-light exposure, may be useful, but additional studies are needed.

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