Understanding circadian responses to light in persons with Mild Cognitive Impairment and Alzheimer's disease

项目总结/文摘

PROJECT SUMMARY/ABSTRACT Severe sleep-wake and circadian system dysfunctions are common in patients afflicted with Alzheimer's disease and related dementias (ADRD). In people with mild cognitive impairment (MCI), an “at risk” or potential prodromal stage of dementia, sleep-wake disturbance is evident in up to 60% of patients. Appropriately timed light exposure has been shown to increase sleep efficiency, decrease agitation, and even limit cognitive decline in the ADRD population, but accurately specifying the stimulus for the human circadian system and developing effective light delivery methods have been identified as the primary challenges for successful treatment. While it is now established that the spectral and absolute sensitivity of the human circadian system is quite different compared to the human visual system, relatively little is known about how retinal light distribution and individual variations in macular pigment optical density (MPOD) affect suppression of melatonin, a circadian biomarker, especially in the aging eye. The proposed study aims to delineate the role of these 2 factors in circadian phototransduction, to enable development of lighting devices delivering precise and tailored circadian-effective doses. Our preliminary data in healthy young adults indicate a higher MPOD was associated with lower melatonin suppression. In this study, we will extend these findings to MCI and age-matched older adults. Specifically, all participants will be treated to 4 innovative lighting interventions consisting of 2 discrete narrowband light sources (blue, λmax = 451 nm; green, λmax = 522 nm) at 2 discrete light distribution patterns: (1) “on-axis”' (i.e., directed along the eye's visual axis to the fovea) and (2) “off-axis” (i.e., directed on the periphery of the eye's visual axis). Given the retinal morphology and the highest density of photoreceptors in the 2° field of view, we hypothesize that, for the same light level, light delivered on-axis will be more effective at suppressing melatonin than light delivered off-axis. The team we have assembled to participate in this project is unique, including a researcher who specializes in human circadian responses to light, another with expertise circadian phototransduction mechanisms and modeling, yet another who is a vision scientist and proposed the first model of human circadian phototransduction (how the retina converts light signals into electrical signals for the biological clock). A secondary outcome will be a better understanding of how MPOD may be associated with cognitive decline and an exploratory outcome will investigate whether MPOD can be used as a biomarker for light sensitivity. If successful, the proposed study will `shed light' on a relatively unexplored avenue of circadian phototransduction and spatial sensitivity, the understanding of which is essential for specifying and implementing a circadian-effective lighting design in healthcare facilities, senior care living facilities, and residences of MCI and ADRD patients. These results will also help us develop light-based interventions designed to deliver a robust light-dark pattern to MCI and ADRD patients, which will promote better sleep and better cognition.