Thursday, 28 September 2017

Older Age, Dementia, and Circadian Rhythms

It is common knowledge that sleep patterns change with age. Older people tend to sleep less, their sleep can be shallow and fragmented. Often they sleep very little at night, spending few hours in bed during the daytime. The problem becomes serious in older people suffering from dementia, especially from the caretaker’s perspective.

Researchers discovered several brain processes that influence these sleeping pattern changes. One particularly interesting finding from this research (which may also inform approaches for addressing the problem) is the finding that light exposure has serious effects on the circadian rhythm in the elderly.

Our visual sensory system performs two major tasks: the gathering and processing of visual information (the visual response), and the control of the biological clock that regulates the production of several important hormones (the non-visual response). The majority of living organisms have a non-visual response to the day-night cycle, where body functions adjust to specific periods within a 24 hour day (circadian cycle).

Circadian rhythms regulate the sleep-wake cycle, body temperature, hormone release (e.g., melatonin and cortisol), and gene expression. Circadian rhythms are not set in stone and have to be fine-tuned to the actual experience of the timing and duration of day and night, which are subject to seasonal changes and geographic location. The importance of synchronized circadian regulation is obvious if we consider the physiological and behavioral disruptions caused by jet lag.

In 2005, our eyes were discovered to have a specific photosensitive cell type named intrinsically photosensitive retinal ganglion cells (ipRGCs) that are primarily involved in the regulation of circadian rhythms. These cells are sensitive to a broad range of wavelengths with maximal light absorption at blue light wavelengths of around 480 nm. It is believed that ipRGCs are tuned to the dominant wavelength of light at twilight. During twilight (i.e., at dawn and dusk) the sun is close to the horizon and there is a relative enrichment of ‘blue’ light in the dome of the sky because of the preferential scattering of short wavelengths of light passing obliquely through the atmosphere.

The signals from ipRGCs are processed in the suprachiasmatic nucleus in the anterior hypothalamus that is considered the key circadian pacemaker in the brain. The suprachiasmatic nucleus regulates the release of melatonin, a hormone crucial to the regulation of sleep and wakefulness, with blue light stimulating the most powerful changes in the melatonin secretion rhythm.

Visual and non-visual systems respond differently to the quantity of light and timing of light exposure. The quantity of polychromatic white light necessary to activate the non-visual circadian system is at least two orders of magnitude greater than the amount that activates the visual system. The reaction time of two systems is also different: while the visual system responds to a light stimulus very quickly (in milliseconds), the duration of light exposure needed to affect the circadian system can take minutes. The effects of light on the circadian system depends on the infusion of melatonin into the bloodstream, increasing the response time.

How circadian rhythms get affected with advanced age?

Our sensitivity to light stimuli reduces with the age. Multiple studies demonstrate that neuronal activity in the suprachiasmatic nucleus is reduced in the elderly, especially after the age of 80, and circadian rhythm amplitude is also reduced after the age of 50. This means that the intensity of the response of the non-visual system to light stimuli is reduced, sometimes very substantially. The direct consequence of this muted response is the lack of proper regulation and adjustment of circadian rhythms to the day/night cycle. 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.

The first stage of phototransduction (when light signals are converted into neural signals) is negatively affected in older people: older adults have reduced optical transmission at short wavelengths that are maximally effective for the regulation of circadian system (i.e., blue light).

Older adults also tend to lead a more sedentary indoor lifestyle, with less access to bright light during the day, potentially increasing the risk for circadian disruption.

It is well-established that visual task performance improves with increased light levels, regardless of age. However, the need for light for visual task performance increases with age due to age-related losses in retinal illumination. These losses are reasonably uniform over time, with a 10% loss per ten years of aging. Thus, a ninety-year-old would require ten times the light of a 10-year-old for similar photoreception. The effect on circadian rhythmicity is further exacerbated with age because the shorter violet and blue wavelengths (400–500 nm) are most affected by yellowing of the aging eye.

It is also worth keeping in mind that older people often have reduced eyesight, suffer from blurred vision, and may have age-related eye diseases such as glaucoma, cataracts, macular degeneration, and other conditions.

How circadian rhythms get affected in neurological conditions?

Neurodegeneration caused by Alzheimer’s disease and similar conditions may affect multiple parts of the brain, including the parts involved in regulation of circadian rhythms. In Alzheimer’s disease, the suprachiasmatic nucleus deteriorates, contributing to alterations in circadian rhythms. This deterioration exacerbates the age-related loss of neuronal activity in the nucleus. Sleep disturbances, agitated behaviour, and depression are very common in people suffering from dementia.

What can be done to counteract these negative changes?

Bright light therapy has emerged as one of the most harmless and effective approaches to manage sleep disturbances in elderly people and patients with dementia.

Researchers have demonstrated that increased exposure to bright light may increase the amplitude of circadian rhythms, i.e., clearly enhances the intensity of the response to daily 24-hour cycles. Bright light exposure during the morning or evenings may help in consolidating circadian rhythms. Additionally, increased exposure to blue light may be beneficial, as photoreceptors in ipRGCs are more easily activated at these wavelengths.

The points above were incorporated into the development of a number of experimental light therapies aimed at stimulating the normal functioning of the non-visual system in the elderly and people with Alzheimer’s disease and dementia.

Light therapy may be delivered in a variety of ways, such as using a light box placed approximately one meter away from the participants at a height within their visual field; a headworn light visor; ceiling mounted light fixtures; or naturalistic light therapy—known as dawn-dusk simulation—that mimics outdoor twilight transitions.

Published research data suggests that circadian rhythm disturbances may be reversed by stimulation of the suprachiasmatic nucleus with light. Clinical research has shown that light therapy can consolidate rest and activity patterns in people with dementia.

There is a diverse choice of various electric light sources these days, and with proper selection, a balanced and circadian-effective lighting regime can be achieved in spaces with insufficient daylight illumination. The spectral characteristics and intensity of electric lights should be adjusted to the time of the day. Currently, the LED Luminaire™ is being developed that auto-tunes interior lighting to mimic the full spectrum of natural daylight throughout the day, with characteristics that can be “tuned” for older adults. This would provide quality illumination for visual tasks and help synchronize biological rhythms for better health, cognitive ability, and performance.

References

Abraha, I., Rimland, J. M., Trotta, F. M., Dellaquila, G., Cruz-Jentoft, A., Petrovic, M., Gudmundsson, A., Soiza, R., O’Mahony, D., Guatita, A., & Cherubini, A. (2017). Systematic review of systematic reviews of non-pharmacological interventions to treat behavioural disturbances in older patients with dementia. The SENATOR-OnTop series. BMJ Open, 7(3). doi: 10.1136/bmjopen-2016-012759

Dimitriou, T., & Tsolaki, M. (2017). Evaluation of the efficacy of randomized controlled trials of sensory stimulation interventions for sleeping disturbances in patients with dementia: a systematic review. Clinical Interventions in Aging, Volume 12, 543-548. doi: 10.2147/cia.s115397

Duffy, J. F., & Czeisler, C. A. (2009). Effect of Light on Human Circadian Physiology. Sleep Medicine Clinics, 4(2), 165-177. doi: 10.1016/j.jsmc.2009.01.004

Ellis EV et al. Chronobioengineering indoor lighting to enhance facilities for ageing and Alzheimer’s disorder. Intelligent Buildings International, 2013b Vol. 5, No. S1, 48–60. Ellis, E. V., Gonzalez, E. W., & Mceachron, D. L. (2013). Chronobioengineering indoor lighting to enhance facilities for ageing and Alzheimers disorder. Intelligent Buildings International, 5(Sup1), 48-60. doi: 10.1080/17508975.2013.807764

Figueiro, M. G. (2017). Light, sleep and circadian rhythms in older adults with Alzheimers disease and related dementias. Neurodegenerative Disease Management, 7(2), 119-145. doi: 10.2217/nmt-2016-0060

Hanford N, Figueiro M. (2013). Light Therapy and Alzheimer’s Disease and Related Dementia: Past, Present, and Future. Journal of Alzheimer’s Disease, 33(4), 913-922. doi: 10.3233/JAD-2012-121645

Weldemichael, D. A., & Grossberg, G. T. (2010). Circadian Rhythm Disturbances in Patients with Alzheimers Disease: A Review. International Journal of Alzheimers Disease, 2010, 1-9. doi: 10.4061/2010/716453

Image via TimHill/Pixabay.

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