This study's main hypothesis is that a delivering a tailored lighting intervention (TLI) will provide a successful means for promoting circadian entrainment and treating metabolic disease and inflammation in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) and Alzheimer's disease and related dementias (ADRD). As such, the proposed studies have the potential to provide important insights into the link between AD/ADRD and type 2 diabetes (T2DM) by identifying the disruption of circadian rhythms as a key component in the metabolic impairment. It would open new avenues of investigation, as it would raise the possibility that brain insulin resistance is indeed a consequence of disrupted circadian rhythm. Preliminary data from ongoing studies demonstrates a beneficial effect of light treatment on sleep and depression. If positive results are observed, the potential also exists to transform the manner in which homes, assisted living facilities, and nursing homes are lighted by delivering a simple, practical, non-pharmacological intervention to promote entrainment, improve sleep, and reduce metabolic disease in AD and mild AD MCI patients.
The specific aims of the proposed research are two-fold. First, a randomized, placebo-controlled, crossover study involving 60 AD/ADRD patients who live in controlled environments (i.e., assisted living facilities and nursing homes), will investigate whether 8 weeks of exposure to a TLI designed to increase circadian entrainment (measured via urinary melatonin) improves sleep (actigraphy and questionnaires), mood (questionnaire), inflammatory markers, and metabolic control (oral glucose tolerance tests) compared to a control, circadian-inactive light. Second, using a single-arm, between-subjects design, placebo- controlled study we will investigate if long-term (6-month) exposure to TLI improves glucose homeostasis and insulin sensitivity in 30 patients with mild AD/ADRD and sleep disturbances, who will be recruited from the Mount Sinai AD research center (ADRC) and randomized to receive TLI (or dim light control treatment) at home. We will test if the TLI improves insulin sensitivity (SI) and glucose disposal (SG) as assessed through the frequently sampled IV glucose tolerance test (FSIVGTT) to dissect mechanisms through which circadian re-entrainment improves metabolism. The strengths of this project are considerable, especially given the unavailability of instruments for measuring personal circadian light exposure patterns. If successful, the study will open the way for a practical, effective non-pharmacological treatment for significantly reducing the two diseases' burden on society and, more directly, on caregivers. The unique, diverse research team is composed of experts in the fields of geriatric psychiatry, endocrinology, and light and circadian research, all of whom have direct access to the clinical population. This project is also highly translational, as the PIs will use the information gathered through this research to work with manufacturers in the development of lighting fixtures for this application.

Public Health Relevance

. Alzheimer?s disease (AD) and Alzheimer?s disease and related dementias (ADRD) are closely associated with type 2 diabetes (T2DM) and other metabolic diseases, perhaps due to insulin resistance that is common to both diseases, but the precise relationship between the diseases remains poorly understood. We hypothesize that a light treatment designed to promote circadian entrainment and reduce inflammation and restore metabolic control will lead to improvements in sleep, measures of depression, glucose homeostasis and insulin action, which in turn will reduce brain insulin resistance and improve cognitive outcomes. The research holds strong potential to contribute to the scientific understanding of both diseases while also providing significant improvements to quality of life among those suffering from AD and ADRD.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
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Mackiewicz, Miroslaw
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Rensselaer Polytechnic Institute
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United States
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