Science: Deep-Dive
Introduction to a Deeper Dive on Science: “The Impact of Lighting on Human Circadian Rhythms" – A White Paper
The light that we are exposed to can have significant impacts on our circadian rhythms; these impacts can, in turn, significantly affect our health. Generally, these correlations are true for humans, but can be even more acute in older adults with dementia, as these conditions themselves can be serious disruptors to their circadian cycles.
Over the past two decades, researchers have made significant advances in the understanding of our circadian systems, how these systems are impacted by the lighting conditions we are exposed to, and how we measure these conditions and control these impacts. Most importantly, Blue Iris Labs is focused on how lighting can be used to support our circadian systems and improve health outcomes for healthy populations, as well as those with specific cognitive diseases.
This White Paper, “The Impact of Lighting on Human Circadian Rhythms”, provides an overview of these issues with a special emphasis placed on the measurement and control of lighting to support the health and well-being of those with Alzheimer’s disease and related dementia (ADRD).
Older Adults and Alzheimer’s Disease
Older Americans (65+) numbered 44.7 million in 2013, representing 14.1% of the U.S. population,1 and by 2030 this older population is estimated to grow to about 72 million. Furthermore, this population is living longer; people reaching age 65 have an average life expectancy of an additional 19.3 years.1 Of the 65+ population, 3.4% lived in nursing homes in 2013. If current trends continue, by 2030 this number will rise to about 10%.
Dementia is a progressive, degenerative disease of the brain. There is no known cure, and there are very few effective treatments. Alzheimer’s disease (AD), the most common form of dementia, is the sixth-leading cause of death in the U.S. and the fifth-leading cause of death for those over the age of 65.2 It is projected that 13.8 million Americans will have AD or a related dementia disorder (ADRD) by 2050.2 More than 70% of people with this disease live at home, and family members and friends provide almost 75% percent of the required care.2 As the disease progresses, families are often forced to move loved ones from home to assisted living facilities. Often, the precipitating factor is disturbed sleep-wake (circadian) cycles, where the person with AD/ADRD is awake at night, causing stress and fatigue to caregivers.3
Light therapy has shown great promise as a nonpharmacological treatment in helping to regulate sleep and in improving cognition in older adults with AD/ADRD. Studies have demonstrated that daytime light exposure can consolidate and increase nighttime sleep efficiency, while increasing daytime wakefulness and reducing evening agitation.4, 5
Download a Presentation on “Lighting Intervention for Alzheimer’s Patients”
(Click here) if you want to download Mariana G. Figueiro’s PhD presentation to the AAIC on
“Lighting Intervention for Alzheimer’s Patients”.
Sleep, Circadian Rhythms and Light
The sleep/wake pattern is directly driven by the timing signals generated by the suprachiasmatic nuclei (SCN), which is known to be compromised by aging and AD. Studies have shown a reduced circadian rhythm amplitude after the age of 50.6, 7 It is hypothesized that some of the neural processes involved in entrainment might be dysfunctional or less effective as we age.8 Disturbances in circadian rhythms leading to poor sleep in older adults can be the result of dysfunctional circadian pathways or a pathway that cannot process light information with as much fidelity. Moreover, older adults not only have reduced optical transmission at short wavelengths, which is maximally effective for the circadian system, they also lead a more sedentary indoor lifestyle, with less access to bright light during the day. In fact, research demonstrates that middle-aged adults receive approximately 58 minutes of bright light per day9 while older adults in assisted-living facilities receive bright light for only 35 minutes per day.10 Finally, changes in the amplitude and timing of melatonin and core body temperature rhythms may occur in older adults. Lower amplitude of melatonin rhythms may be associated with reduced sleep efficiency and deterioration of internal circadian rhythms, such as hormone production, alertness, and performance.11, 12, 13
In order to maintain synchronization in the face of these physiological changes, it is necessary both to increase the strength of the light stimulus and to design an intervention that is maximally effective for entraining the circadian systems of those with AD/ADRD. A 24-hour light-dark pattern incident on the retina is the most efficacious stimulus for entraining the circadian system in humans.14 In fact, a carefully orchestrated light-dark pattern has been shown in several controlled studies of older populations, with and without ADRD, to be a powerful nonpharmacological tool to improve sleep efficiency and consolidation.15-17
More recently, work from our collaborators at the Lighting Research Center at Rensselaer Polytechnic Institute (LRC) showed increased sleep efficiency and reduced depression and agitation behavior after only 4 weeks of a tailored lighting intervention (TLI).18 However, current approaches to light therapy for reducing sleep disturbances, depression and agitation in older adults do not consider the complete 24-hour light-dark pattern they experience, nor do they integrate light treatment into a practical delivery system, thus compromising their therapeutic value.19 More importantly, the light dose is never measured because, except for the calibrated personal light exposure devices developed by our collaborators, there is no other personal or ambient light measuring device that allows users or researchers to measure the dose actually experienced by patients.
Our work under our NIH grant aims to address need by building upon a patented lighting control system we have developed20 so that it measures the ambient circadian light and provides feedback to the user and to the lighting in the space to assure the correct dose is being delivered at all times.
Lighting Characteristics Affecting the Circadian System
Light is formally defined as optical radiation reaching the human retina that provides visual sensation. All current light sources and light meters are calibrated based on the characteristics of the light affecting our visual system. There are five important characteristics of light for both the human visual and circadian systems: quantity (or level), spectrum, timing, duration, and distribution. The ideal characteristics for vision are, however, quite different from those that are most effective for stimulating the circadian system. In brief, the quantity of polychromatic white light necessary to activate the circadian system is significantly greater than the amount that activates the visual system (measured through melatonin suppression or phase shift). The spectral sensitivity of the circadian system peaks at short wavelengths,21, 22 while the visual system is most sensitive to the middle wavelength portion of the visible spectrum. Operation of the visual system does not depend significantly on the timing of light exposure; it responds well to a light stimulus at any time of the day or night. However, depending on the timing of light exposure, light can phase advance or phase delay the biological clock.23 In addition, while the visual system responds to a light stimulus very quickly (less than one second), the duration of light exposure needed to affect the circadian system can take much longer. For example, to achieve measurable melatonin suppression from exposure to a moderate amount of light in young adults, the required duration of light exposure is at least 5 to 10 minutes.24, 25 For the visual system, spatial light distribution is critical (e.g., when reading black text on white paper), while the circadian system does not respond to spatial patterns.26, 27 It is also important to note that the short-term history of light exposure affects the circadian system’s sensitivity to light. For example, the higher the exposure to light during the day (e.g., 4 hours per day for one week to outdoor light), the lower the sensitivity of the circadian system to light at night, as measured by nocturnal melatonin suppression.28
Measuring and Characterizing Circadian Light and Circadian Stimulus
In 2005, Rea et al. proposed a mathematical model of human circadian phototransduction based on the neuroanatomy and neurophysiology of the human retina and using published action spectrum data for acute melatonin suppression.29 30 Using this model, the spectral irradiance at the cornea is first converted into circadian light (CLA), which is comparable to photopic illuminance but weighted by the spectral sensitivity of the human circadian system as measured by acute melatonin suppression after a 1-hour exposure. Then the circadian stimulus (CS) is determined, which reflects the effectiveness of the spectrally weighted irradiance at the cornea from threshold (CS = 0.1) to saturation (CS = 0.7). While CS was developed using data from studies that measured acute melatonin suppression, Zeitzer et al.31 showed that acute melatonin suppression and phase shifting of melatonin rhythms followed similar threshold and saturation response characteristics. The model has been successfully used to predict the effectiveness of various light sources for activating the circadian system in laboratory32-37 and field studies.38-42
References
1. U.S. Department of Health and Human Services Administration on Aging. A Profile of Older Americans:
2014 2014; Available from: http://www.aoa.acl.gov/Aging_Statistics/Profile/2014/docs/2014-Profile.pdf.
2. Alzheimer’s Association. Alzheimer’s Association Website. 2016; Available from: http://www.alz.org.
3. Ancoli-Israel S, Parker L, Sinaee R, Fell RL and Kripke DF. Sleep fragmentation in patients from a nursing
home. Journal of Gerontology. 1989; 44: M18-21.
4. Ancoli-Israel S, Martin JL, Gehrman P, Shochat T, Corey-Bloom J, Marler M, Nolan S and Levi L. Effect of
light on agitation in institutionalized patients with severe Alzheimer disease. The American Journal of Geriatric
Psychiatry. 2003; 11: 194-203.
5. Ancoli-Israel S, Martin JL, Kripke DF, Marler M and Klauber MR. Effect of light treatment on sleep and
circadian rhythms in demented nursing home patients. Journal of the American Geriatrics Society. 2002; 50: 282-9.
6. Hofman MA and Swaab DF. Alterations in circadian rhythmicity of the vasopressin-producing neurons of
the human suprachiasmatic nucleus (SCN) with aging. Brain Research. 1994; 651: 134-42.
7. Hofman MA and Swaab DF. Living by the clock: the circadian pacemaker in older people. Ageing Res Rev.
2006; 5: 33-51.
8. Skene D and Swaab D. Melatonin rhythmicity: effect of age and Alzheimer’s disease. Experimental
Gerontology. 2003; 38: 199-206.
9. Espiratu R, Kripke D, Ancoli-Israel S and al. e. Low illumination experienced by San Diego adults:
Association with atypical depressive symptoms. Soc Biol Psychiatry. 1994; 35: 403-7.
10. Sanchez R, Ge Y and Zee P. A comparison of the strength of external zeitgeber in young and older adults.
Sleep Res. 1993; 22: 416.
11. Karasek M. Melatonin, human aging, and age-related diseases. Experimental Gerontology. 2004; 39: 1723-9.
12. Van Someren EJ, Raymann RJ, Scherder EJ, Daanen HA and Swaab DF. Circadian and age-related
modulation of thermoreception and temperature regulation: mechanisms and functional implications. Ageing
Res Rev. 2002; 1: 721-78.
13. Duffy JF, Dijk DJ, Klerman EB and Czeisler CA. Later endogenous circadian temperature nadir relative to
an earlier wake time in older people. American Journal of Physiology. 1998; 275: R1478-87.
14. Refinetti R. Circadian Physiology. 2nd ed. Boca Raton, London, New York: CRC Taylor & Francis, 2006.
15. Figueiro M, Eggleston G and Rea M. Effects of Light Exposure on Behavior of Alzheimer’s Patients – A Pilot
Study. Light and Human Health: EPRI/LRO 5th International Lighting Research Symposium. 2002: 151-6.
16. Figueiro M and Rea M. LEDs: Improving the sleep quality of older adults. Proceedings of the CIE Midterm
Meeting and International Lighting Congress. Leon, Spain2005.
17. Figueiro MG SE, Rea M, Kubarek K, Cunningham J, Rea MS. Developing Architectural Lighting Designs to
Improve Sleep in Older Adults. The Open Sleep Journal. 2008; 12: 40-51.
18. Figueiro MG, Plitnick B, Lok A, Jones G, Higgins P, Hornick T and Rea MS. Tailored lighting intervention
improves measures of sleep, depression and agitation in persons with Alzheimer’s disease and related
dementia living in long-term care facilities. Clinical Interventions in Aging. 2014; 9: 1527-37.
19. Montgomery P and Dennis J. Bright light therapy for sleep problems in adults aged 60+. The Cochrane
Database of Systematic Reviews. 2002: CD003403.
20. Page ER, inventor; Erik Page & Associates, Inc., assignee. Movable illuminance sensors for fixture light
sources. U.S. patent 8,536,505. 2013 September 17.
21. Brainard GC, Hanifin JP, Greeson JM, Byrne B, Glickman G, Gerner E and Rollag MD. Action spectrum for
melatonin regulation in humans: evidence for a novel circadian photoreceptor. Journal of Neuroscience. 2001; 21:
6405-12.
22. Thapan K, Arendt J and Skene DJ. An action spectrum for melatonin suppression: evidence for a novel nonrod, non-cone photoreceptor system in humans. The Journal of Physiology. 2001; 535: 261-7.
23. Jewett ME, Rimmer DW, Duffy JF, Klerman EB, Kronauer RE and Czeisler CA. Human circadian
pacemaker is sensitive to light throughout subjective day without evidence of transients. American Journal of
Physiology. 1997; 273: R1800-9.
24. Berson DM, Dunn FA and Takao M. Phototransduction by retinal ganglion cells that set the circadian clock.
Science. 2002; 295: 1070-3.
25. McIntyre IM, Norman TR, Burrows GD and Armstrong SM. Human melatonin suppression by light is
intensity dependent. Journal of Pineal Research. 1989; 6: 149-56.
26. Lasko T, Kripke D and Elliot J. Melatonin suppression by illumination of upper and lower visual fields.
Journal of Biological Rhythms. 1999; 14: 122-5.
27. Visser EK, Beersma DG and Daan S. Melatonin suppression by light in humans is maximal when the nasal
part of the retina is illuminated. Journal of Biological Rhythms. 1999; 14: 116-21.
28. Hébert M, Martin SK, Lee C and Eastman CI. The effects of prior light history on the suppression of
melatonin by light in humans. Journal of Pineal Research. 2002; 33: 198-203.
29. Rea MS, Figueiro MG, Bullough JD and Bierman A. A model of phototransduction by the human circadian
system. Brain Research Reviews. 2005; 50: 213-28.
30. Rea MS, Figueiro MG, Bierman A and Hamner R. Modelling the spectral sensitivity of the human circadian
system. Lighting Research & Technology. 2012; 44: 386-96.
31. Zeitzer JM, Dijk D-J, Kronauer RE, Brown EN and Czeisler CA. Sensitivity of the human circadian
pacemaker to nocturnal light: melatonin phase resetting and suppression. The Journal of Physiology. 2000; 526:
695-702.
32. Wood B, Rea MS, Plitnick B and Figueiro MG. Light level and duration of exposure determine the impact of
self-luminous tablets on melatonin suppression. Applied Ergonomics. 2013; 44: 237-40.
33. Figueiro MG, Wood B, Plitnick B and Rea MS. The impact of light from computer monitors on melatonin
levels in college students. Neuro Endocrinology Letters. 2011; 32: 158-63.
34. Rea MS and Figueiro MG. A working threshold for acute nocturnal melatonin suppression from “white”
light sources used in architectural applications. Journal of Carcinogenesis & Mutagenesis. 2013; 4: 1000150.
35. Figueiro MG, Bierman A and Rea MS. Retinal mechanisms determine the subadditive response to
polychromatic light by the human circadian system. Neuroscience Letters. 2008; 438: 242-5.
36. Figueiro MG, Lesniak NZ and Rea MS. Implications of controlled short-wavelength light exposure for sleep
in older adults. BMC Research Notes. 2011; 4: 334.
37. Figueiro MG, Bierman A, Plitnick B and Rea MS. Preliminary evidence that both blue and red light can
induce alertness at night. BMC Neuroscience. 2009; 10: 105.
38. Young CR, Jones GE, Figueiro MG, Soutière SE, Keller MW, Richardson AM, Lehmann BJ and Rea MS. Atsea trial of 24-h-based submarine watchstanding schedules with high and low correlated color temperature
light source. Journal of Biological Rhythms. 2015; 30: 144-54.
39. Figueiro M, Plitnick B and Rea M. Research Note: A self-luminous light table for persons with Alzheimer’s
disease. Lighting Research & Technology. 2016; 48: 253-9.
40. Figueiro MG, Plitnick BA, Lok A, Jones GE, Higgins P, Hornick TR and Rea MS. Tailored lighting
intervention improves measures of sleep, depression, and agitation in persons with Alzheimer’s disease and
related dementia living in long-term care facilities. Clinical Interventions in Aging. 2014; 9: 1527-37.
41. Figueiro MG, Steverson B, Heerwagen J, Kampschroer K, Hunter CM, Gonzales K, Plitnick B and Rea MS.
The impact of daytime light exposures on sleep and mood in office workers. Sleep Health. 2017; 3: 204-15.
42. Figueiro MG and Rea MS. Office lighting and personal light exposures in two seasons: Impact on sleep and
mood. Lighting Research & Technology. 2016; 48: 352-64