Bright light improves sleep in patients with Parkinson’s disease: possible role of circadian restoration

Abstract

parkinson's disease (pD) is one of the most common neurodegenerative disorders. Among the most common manifestations of PD are sleep problems, which are coupled with the adverse effects of dopaminergic therapies (Dt). A non-pharmacological solution for these sleep problems has been sought to avoid additional pharmacological intervention. Here, we show that bright light therapy (BLT) is effective for improving sleep in Japanese PD patients receiving DT. Furthermore, experimental evaluation of peripheral clock gene expression rhythms revealed that most PD patients receiving DT who experienced improved sleep following BLT showed a circadian phase shift, indicating the existence of a correlation between circadian modulation and sleep improvement. conversely, this result indicates that sleep problems in pD patients receiving Dt may arise at least in part as a result of circadian dysfunction. indeed, we found that chronic dopaminergic stimulation induced a rapid attenuation of autonomous oscillations of clock gene expression in ex vivo cultured mouse suprachiasmatic nucleus (Scn) at the single neuron level. in conclusion, BLt is a promising medical treatment for improving sleep in pD patients receiving Dt. this BLt-induced improvement may be due to the restoration of circadian function. Parkinson's disease is one of the most common neurodegenerative disorders, affecting approximately 10 million people worldwide 1. First-line treatment strategies involve implementation of dopaminergic therapies such as dopamine replacement therapy using levodopa which is converted to dopamine by enzymes in the brain 2,3. Among the most common manifestations of PD are sleep problems, which reduce quality of life and impair daytime functioning. For example, in a large survey of non-motor symptoms, 64% of PD patients reported sleep problems, representing the second most common non-motor complaint 4. Previous studies have suggested that PD symptoms and the adverse effects of medications may be some of the causes of sleep problems in PD patients 5-7. Because of the risk of interference with treatment regimens, few treatment options for sleep problems in PD are available; in particular, chronic sleep problems are coupled with the adverse effects of the medications prescribed for PD. Therefore, preventing sleep problems in patients with PD requires the development of non-pharmacological approaches. Several lines of evidence suggest that one cause of sleep problems in patients with PD is circadian dysfunction. First, dopaminergic therapy (DT)-receiving PD patients show a circadian phase advance and decrease in nighttime levels of melatonin 8,9. Melatonin is a pineal hormone whose circadian secretion is regulated by the hypothalamic SCN, the center of the circadian clock, via a polysynaptic efferent pathway 10. Concurrently, melatonin is thought to play a role in enhancing the robustness of suprachiasmatic circadian function by activating

Bright Light Therapy for Parkinson Disease: A Literature Review and Meta-Analysis of Randomized Controlled Trials

“…However, one study was excluded from the meta-analysis due to the combination of BLT with cognitive behavioral therapy in the interventional group. The rest of the five studies [ 22 , 23 , 24 , 25 , 26 ] were either open-label, single-arm clinical trials or retrospective observational studies focusing on the PD users of BLT. Those six studies excluded from the meta-analysis are summarized in Table 1 .…”

Impact of light therapy on rotating night shift workers: the EuRhythDia study

“…The role of bright light therapy in restoring appropriate circadian rhythms has been reported in studies of patients diagnosed with both Alzheimer’s and Parkinson’s disease [ 25 ]. While the mechanisms remain unclear, bright light therapy may provide relief by targeting absolute and relative expression levels of circadian clock genes .…”

It’s About Time: The Circadian Network as Time-Keeper for Cognitive Functioning, Locomotor Activity and Mental Health

“…The study evaluated the expression of three core-clock genes NR1D1 , NR1D2, and PER3 in comparison to a control group. Patients received BLT once a day in the evening (19–21 h) for approximately 3 months and hair samples were collected prior to and following the BLT protocol with a sampling interval of 6 h during one circadian day ( Endo et al, 2020 ). A significant correlation between the peak expression time of PER3 before and after BLT was documented, which revealed a significant phase delay in most patients following the BLT treatment ( Endo et al, 2020 ).…”

“…Patients received BLT once a day in the evening (19–21 h) for approximately 3 months and hair samples were collected prior to and following the BLT protocol with a sampling interval of 6 h during one circadian day ( Endo et al, 2020 ). A significant correlation between the peak expression time of PER3 before and after BLT was documented, which revealed a significant phase delay in most patients following the BLT treatment ( Endo et al, 2020 ). In addition, while no significant association was found between sleep related parameters using the Epworth Sleepiness Scale (ESS) ( Johns, 1991 ), a self-report measure to assess daytime sleepiness, a correlation of sleep improvement with the delayed phase of PER3 was reported in PD Sleep Scale 2 scores (PDSS-2), a metric to quantify the level of sleep disturbance ( Endo et al, 2020 ).…”