R01AG072762

The use of rhythmic light therapy to entrain gamma oscillations and the circadian system in patients with Alzheimer's disease and related dementias (ADRD) - Project Summary/Abstract

Data suggest that approximately 40% of the estimated 5.5 million older (65+) Americans with Alzheimer's disease (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 Alzheimer'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 amyloid-beta (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 exciting pilot data showing that light modulating at 40 Hz increases gamma power and gamma/theta coupling, both associated with an 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 delivering 40 Hz to promote gamma wave entrainment (rhythmic light [RL]) affects subjective sleep and cognition 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 intervention, 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 intervention 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 burdens, 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 progression of the disease MCI and mild AD. We have the experience, expertise, and ability to recruit the participants for the study.

Icahn School Of Medicine At Mount Sinai

TO ENCOURAGE BIOMEDICAL, SOCIAL, AND BEHAVIORAL RESEARCH AND RESEARCH TRAINING DIRECTED TOWARD GREATER UNDERSTANDING OF THE AGING PROCESS AND THE DISEASES, SPECIAL PROBLEMS, AND NEEDS OF PEOPLE AS THEY AGE. THE NATIONAL INSTITUTE ON AGING HAS ESTABLISHED PROGRAMS TO PURSUE THESE GOALS. THE DIVISION OF AGING BIOLOGY EMPHASIZES UNDERSTANDING THE BASIC BIOLOGICAL PROCESSES OF AGING. THE DIVISION OF GERIATRICS AND CLINICAL GERONTOLOGY SUPPORTS RESEARCH TO IMPROVE THE ABILITIES OF HEALTH CARE PRACTITIONERS TO RESPOND TO THE DISEASES AND OTHER CLINICAL PROBLEMS OF OLDER PEOPLE. THE DIVISION OF BEHAVIORAL AND SOCIAL RESEARCH SUPPORTS RESEARCH THAT WILL LEAD TO GREATER UNDERSTANDING OF THE SOCIAL, CULTURAL, ECONOMIC AND PSYCHOLOGICAL FACTORS THAT AFFECT BOTH THE PROCESS OF GROWING OLD AND THE PLACE OF OLDER PEOPLE IN SOCIETY. THE DIVISION OF NEUROSCIENCE FOSTERS RESEARCH CONCERNED WITH THE AGE-RELATED CHANGES IN THE NERVOUS SYSTEM AS WELL AS THE RELATED SENSORY, PERCEPTUAL, AND COGNITIVE PROCESSES ASSOCIATED WITH AGING AND HAS A SPECIAL EMPHASIS ON ALZHEIMER'S DISEASE. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.866 - Aging Research

National Institute on Aging (NIA) [HHS - NIH]

New York, New York 100296504 United States

Single Zip Code

Research Project Grant (Parent R01 Clinical Trial Required) (PA-20-183)

Amendment Since initial award the End Date has been extended from 07/31/26 to 07/31/27 and the total obligations have increased 301% from $792,504 to $3,174,975.