Circadian dysfunction blamed for sleepiness in PD patients

By Eleanor McDermid, Senior medwireNews Reporter

Patients with Parkinson’s disease (PD), particularly those with excessive daytime sleepiness, have reduced melatonin levels and amplitude of the melatonin circadian rhythm, research shows.

“These findings suggest an important and novel role of circadian regulation in the manifestation of the excessive sleepiness associated with PD,” say the study authors, led by Aleksandar Videnovic (Massachusetts General Hospital, Boston, USA).

For the study, 20 PD patients on stable therapy and 15 age-matched controls had serum samples taken every 30 minutes for 24 hours. The researchers note that they sampled more frequently than in some previous studies that did not find differences in melatonin between PD patients and controls.

“More frequent sampling increased our ability to determine the timing of the melatonin rhythm more accurately,” they write in JAMA Neurology. They also believe that their study more fully accounted for confounding factors that could have influenced circadian rhythms.

Although PD patients had a clear circadian rhythm of melatonin secretion, melatonin amplitude was significantly blunted, at 18.6 pg/mL compared with 77.2 pg/mL in controls. This was blunted still further in the 60% of patients with excessive daytime sleepiness, defined as an Epworth Sleepiness Scale score of 10 or higher, at 10.8 pg/mL compared with 30.2 pg/mL in patients without excessive sleepiness.

PD patients were significantly more likely than controls to have excessive daytime sleepiness, at 60% versus 27%, despite having similar self-reported sleep quality.

Overall melatonin secretion was also significantly reduced in the PD patients, with an area under the curve of 332.7, compared with 1322.7 in controls. Again, this was even more pronounced in PD patients with daytime sleepiness, at 189.7 versus 574.2 in those without. Melatonin secretion was suppressed both during the daytime and at night.

The team found no association between total levodopa equivalent dose and melatonin levels or rhythms, but say that this “needs to be explored further in PD patients naive to dopaminergic medications.”

Lower melatonin secretion and amplitude was associated with older age in the PD patients, but not in the controls. No other factors, including PD duration and severity, were associated with melatonin measures in the patients.

The researchers suggest that “therapeutic approaches aimed at strengthening circadian function, such as timed exposure to bright light, melatonin administration, and modifications of physical activity, may have potential as complementary therapies for impaired sleep-wake cycles in the PD population.”

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