The Use of Rhythmic Light Therapy to Entrain Gamma Oscillations and the Circadian System in Patients with Alzheimer's Disease and Related Dementias (ADRD)

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Project Summary/Abstract Data suggest that approximately 40% of the estimated 5.5 million older (65+) Americans with Alzheimer's dis- ease (AD) suffer from severe dysfunction of sleep-wake and circadian systems 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. Our team has published various studies showing the positive impact on sleep, mood, and behavior of a tailored lighting intervention (TLI) designed to promote circadian entrainment in persons with Alz- heimer’s disease and related dementias (ADRD). In addition, coherent 40 Hz neural oscillation, shown to be important for healthy brain activity, is reduced in those with neurodegenerative diseases. Research showed that exposure to 40 Hz rhythmic light (RL) decreased Aβ levels as well as plaque pathology in the visual cortex in a 6-month-old AD transgenic mouse model. In addition, we recently collected and published on exciting pilot data showing that light modulating at 40 Hz increases gamma power and gamma/theta coupling, both associated with increase in memory and cognition. The main goal of this proposal is to investigate the impact of a combination of light for promoting circadian entrainment and light for promoting gamma oscillation entrainment on sleep and cognition in MCI and mild AD patients living in the community. In Aim 1, we will investigate how light deliver- ing 40 Hz to promote gamma wave entrainment (rhythmic light [RL]), affects subjective sleep and cogni- tion in a controlled laboratory study. A lab study will allow us to collect electroencephalogram (EEG) data, perform cognitive tests, and observe the response in those with MCI compared to a healthy control group (HC). In Aim 2, we will deliver, in a randomized, placebo-controlled field study, the combined in- tervention, delivering light for circadian entrainment (TLI) and light for gamma power entrainment (40 Hz RL), for a period of 8 weeks and measure nocturnal melatonin (a marker of circadian entrainment), sleep, and cognition. We hypothesize that better sleep resulting from the combined intervention (TLI + RL) will increase nighttime melatonin levels and improve cognition in MCI and mild AD patients living in the community. We will, for the first time, demonstrate that a practical, effective, tailored, nonpharmacological in- tervention using light that promotes circadian entrainment (TLI) and delivers neurostimulation (40 Hz RL) can be used to improve sleep and cognition in older adults with MCI and mild AD living at home or in independent or assisted living facilities. This approach has the potential to thereby mitigate significant financial and social bur- dens, including decreasing cognitive deterioration in this population. Moreover, given recent evidence linking the importance of sleep in the development of AD, the proposed studies can have a significant impact on the pro- gression of the disease MCI and mild AD. We have the experience, expertise, and ability to recruit the partici- pants for the study.