Light therapy and Parkinson’s disease
Light therapy, or the use of light as a treatment for disease, is being investigated in many neurologic conditions including as a treatment for some of the symptoms of Parkinson’s disease (PD). Light therapy encompasses a large category of treatments involving different types of light and delivery systems. More research still needs to be done to figure out exactly what type of light therapy works for which symptoms of PD.
To better understand what we do and do not know about light therapy for PD, this week I will explore:
- What are the variables to consider when thinking about light therapy?
- Which symptoms of PD may experience relief with light therapy?
- Are there any currently available devices for light therapy to treat PD symptoms?
- What clinical trial data supports the use of light therapy in PD?
- Are there current light therapy clinical trials that are enrolling people with PD?
- Why might light therapy be helpful in PD?
The many variables of light therapy
There is a very long list of variables to consider when thinking about how light can be delivered as a treatment and each variable could affect the light’s therapeutic potential.
What part of the light spectrum is being used?
Three wavelengths of light therapy are being considered for Parkinson’s disease:
- The full spectrum of light (also called polychromatic light or white light)
- Near infrared light (NIR in the wavelength range of 670-1300 nanometers)
- Blue light (wavelength range of 460-480 nanometers) – this light is thought to be most effective to influence the body’s own biological clock
How is the light being delivered?
In studies using white light, the eyes are used to detect the light. The light is therefore delivered via a lightbox or a screen.
Near Infrared Light (NIR) is not in the wavelength range that is detectable by eye. It is thought that to be used as a therapy, it needs to be delivered more directly to brain tissue. Therefore, other delivery methods have been devised.
Additional delivery methods include:
- Via a helmet containing light sources that is worn on the head – the light is meant to penetrate through the skin and skull
- Intranasally
- Via a light-emitting device that is implanted in the brain
What is the brightness of the light?
Many clinical trials for light therapy used Lux levels in the 10,000 range. Light brightness per area is measured in Lux. A moonless night would register 0.0001 Lux. A very dark overcast day would register 100 Lux. Full daylight (but not direct sunlight) would register 10,000 Lux.
What is the length of a session of light therapy?
For light therapy to be feasible to incorporate into a person’s day, a practical amount of time spent in front of the light needs to be selected. Past trials have used times ranging from 30 min to 1.5 hours a day.
How many sessions of light therapy are given?
Variables to consider here include how often would the therapy need to be given during the day (once, twice)? How many times a week? For how many weeks? Does the treatment need to be ongoing or do the effects of the treatment last after the treatments are stopped?
What time of day is the therapy given?
Whether the light should be presented in the morning, or the evening or both can be adjusted as well.
Each of these variables can have implications on the effectiveness of the treatment. And each therefore needs to be tested in clinical trials to determine the best set of variables to use for optimal results.
Which symptoms of PD are potentially treatable with light therapy?
A variety of PD symptoms have been considered as potentially amenable to treatment with light therapy. We have included additional resources on these symptoms below:
Sleep Disorders
In this video discussion entitled Dr. Gilbert Hosts: Sleep Issues & Parkinson’s Disease, Dr. Maria Ospina and Dr. Gilbert answer questions about difficulties with sleeping. Around the 40 minute mark, there is some information about how blue light can affect your sleep.
Depression
Within this document, Depression and Parkinson’s Disease, there is further explanation about this symptom.
Anxiety
In this article, we explore the relationship between stress, anxiety and Parkinson’s disease.
Fatigue
Learn more about fatigue in our document entitled Fatigue in Parkinson’s Disease.
Motor Function
To learn more about the motor symptoms of Parkinson’s we have more information about the many symptoms and their signs.
Available light therapy devices
Because light therapy delivered via the eyes or the skin has minimal side effects, multiple light-emitting devices have already been designed, marketed, and are available for purchase without FDA approval.
These white light and red-light devices are currently marketed for treatment of depression, chronic pain, wrinkles, wound healing, acne, and sleep improvement. There are no white light or red-light therapy devices yet on the market that are designed and marketed specifically for Parkinson’s disease.
Past data on light therapy for Parkinson’s disease
Many studies of light therapy in animal models of PD have supported the testing of light therapy in people with PD.
There have been nine completed clinical trials so far. Seven investigated white light, one investigated blue light, and one investigated NIR light, and each selected a set of variables to utilize in conducting the clinical trial. The white light trials tested intensities ranging from 1000-10,000 lux and duration of light exposure ranging from 30 minutes to 1.5 hours. The trials also varied when the light stimulation was presented – either in the morning (1 hour after awakening), in the evening (1 hour before bedtime) or twice daily.
Although the trials were small, all of them showed promising results as it related to improvement of various PD symptoms.
Trial: Case series 2007
Light parameters: 1000-1500 Lux for 1-1.5 hours, one hour prior to sleep
# of patients: 12
Results: Improvement in various motor and non-motor symptoms
Author: Willis and Turner
Reference: https://pubmed.ncbi.nlm.nih.gov/17612949/
Trial: Randomized controlled 2007
Light parameters: 7500 Lux vs 950 Lux for 30 min, one hour after awakening
# of patients: 36
Results: Bright light led to significant improvement of tremor, United Parkinson Disease Rating Scale (UPDRS) I, II, and IV, and depression as compared to control light therapy. Daytime sleepiness improved in both groups.
Author: Paus, et al
Reference: https://pubmed.ncbi.nlm.nih.gov/17516492/
Trial: Open label 2012
Light parameters: 4000-6000 Lux for one hour, right before bedtime
# of patients: 129
Results: Significant improvement in depression and insomnia, but exposure to light did not improve motor function
Author: Willis, et al
Reference: https://pubmed.ncbi.nlm.nih.gov/22499678/
Trial: Randomized, controlled 2013
Light parameters: 10,000 Lux for 30 min, either in morning or at night + cognitive behavioral therapy (CBT) vs 10 mg doxepin vs red light (placebo)
# of patients: 18
Results: Doxepin showed the best results. Light therapy +CBT showed some improvements on sleep scales, but was associated with decline in Parkinson Disease Questionnaire-39
Author: Rios Remenets, et al
Reference: https://pubmed.ncbi.nlm.nih.gov/23561946/
Trial: Randomized controlled 2017
Light parameters: 10,000 Lux vs dim red light for one hour twice daily
# of patients: 31
Results: Bright light resulted in significant improvements in multiple sleep metrics as well as increased physical activity
Author: Videnovic, et al
Reference: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5470356/
Trial: Open label 2018
Light parameters: 3000-4000 Lux for 1 hour, right before bedtime
# of patients: 140
Results: Improvement of insomnia and reduction of REM behavior sleep disorder symptoms
Author: Martino, et al
Reference: https://pubmed.ncbi.nlm.nih.gov/29530365/
Trial: Randomized controlled 2019
Light parameters: 10,000 Lux vs 200 Lux for 30 minutes twice daily
# of patients: 83
Results: Depression improved in both groups
Author: Rutten, et al
Reference: https://pubmed.ncbi.nlm.nih.gov/30770426/
Trial: Open label 2019
Light parameters: Experience of patients who use blue light glasses on a regular basis
# of patients: 58
Results: Improvement in sleep, depression and motor functioning
Author: Smilowska, et al
Reference: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6604290/
Trial: Randomized controlled 2021
Light parameters: Transcranial, intranasal, neck and abdomen transdermal NIR treatment
# of patients: 12
Results: Improvement in measures of mobility, cognition, balance and fine motor skills
Author: Liebert, et al
Reference: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249215/
Trial: Open label 2021
Light parameters: NIR treatment of the posterior aspect of the neck midline, pointing to the midbrain + ingestion of hydrogren water
# of patients: 18
Results: UPDRS Parts I, II, III improved
Author: Hong, et al
Reference: https://pubmed.ncbi.nlm.nih.gov/33530211/
Trial: Randomized, controlled 2021
Light parameters: Transcranial and intra-oral infrared light
# of patients: 22
Results: Montreal cognitive assessment remained stable over the 4 weeks of treatment. There were some trends to improvement in fine motor tasks, but did not reach statistical significance
Author: Bullock-Saxton, et al
Reference: https://pubmed.ncbi.nlm.nih.gov/34092640/
Current clinical trials for light therapy
There are several clinical trials for various light therapy protocols that are currently enrolling people with PD. If you are interested in learning more or participating in one of the trials, the links below will lead you to further information.
Clinical trials of white light:
Bright vs dim light
Bright light therapy is being compared to dim red-light therapy delivered twice daily. Outcome measures include an assessment of excessive daytime sleepiness and a general scale of non-motor symptoms in PD.
SunRay light boxes
This trial will also compare bright white vs. dim red light stimulation, with light to be administered via the SunRay light box. Outcome measures include assessment of sleep and fatigue.
DayVia lamp
This trial will compare bright light (10,000 Lux) vs control light. The outcome measures will be United Parkinson Disease Rating Scale (UPDRS) scores.
PhotoPharmics Celeste device
The DB RCT for Specialized Phototherapy trial will compare the Celeste device to a control light. PDQ 39, a measurement of quality of life, will be the primary outcome measure. Other endpoints will be UPDRS scores of motor and non-motor symptoms. This trial has not started yet.
Clinical trials of NIR light:
Intracerebral NIR 670 nm implanted device
The Clinical Trial for Near Infrared Endoventricular Illumination is taking place in France and is being conducted by one of the pioneers in deep brain stimulation (DBS) surgery. In this trial, a device is implanted in the brain that emits NIR light.
Transcranial and intranasal NIR stimulation
This trial is testing two other delivery methods of NIR light – a helmet with light sources and intranasal delivery.
Why might light therapy work for PD?
Research, primarily in animal models of PD, have investigated potential mechanisms by which light therapy might deliver positive effects on symptoms.
Here are three theories:
- Light acts directly to reset the body’s master clock. The system of circadian rhythms controls the aspects of human physiology that cycle as a function of time of day – chief of which is sleep and wakefulness. Light, sensed by the eyes, is the key (but not only) regulator of this system. The suprachiasmatic nucleus, which is a brain structure that is located behind the eyes, is the body’s master clock.
Abnormalities of the circadian system are becoming an increasingly well-established non-motor symptom of PD. External light can potentially regulate the master clock that is not working properly. Interestingly, several studies have indicated that exposure to blue light (460 nm) is more effective than other wavelengths at resetting the circadian rhythm clock. Therefore, if manipulation of circadian rhythm is the mechanism by the light therapy exerts its effects on PD symptoms, it is possible that blue light might be the optimal one to use. Only one small open label study investigated blue light for PD symptoms. More research is therefore necessary.
- Light may enhance dopamine transmission. Multiple lines of research in animal models suggest that light can have a direct effect on the dopamine system, and this may be the mechanism of action by which light improves PD symptoms.
- Near-infrared light is absorbed by cytochrome C-oxidase in the mitochondria, the energy-manufacturing component of the cell. This absorption is thought to have a variety of effects including increasing energy production and regulating cell signaling. Mitochondrial dysfunction is well established to play a role in the development of PD and near infrared light may therefore be able to undo some of this dysfunction.
There is much promise in the use of light therapy to treat symptoms of PD, but much is yet unknown. The most robust data is available for the use of white light therapy for the treatment of insomnia in PD – however, the current data is not clear on exactly how and when to deliver the therapy for maximal benefit. We await the results of the current clinical trials for additional guidance.
A special thank you to Dr. Aleksander Videnovic, Associate Professor of Neurology at Harvard Medical School and Director of the Division of Sleep Medicine at Massachusetts General Hospital, for reviewing this post.
Tips and Takeaways
- A variety of PD symptoms may respond to light therapy including motor function, depression, anxiety, sleep disorders and fatigue
- The initial research is promising; however, more research is being done to determine exactly what type of light therapy works for which symptoms of PD
- Nine clinical trials of light therapy for symptoms of PD have been completed and more are underway
- Light therapy may work by adjusting the circadian rhythm clock, by enhancing dopamine transmission or by improving energy production in the nerve cells
本文引用自: https://www.apdaparkinson.org/article/light-therapy-for-parkinsons-disease/
