# Non-invasive lighting treatment as a novel therapeutic for age-related cognitive decline

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA BERKELEY · 2023 · $228,137

## Abstract

Project Summary
 Cognitive decline is pervasive with advancing age, with an estimated 50 million people presently living with
dementia worldwide. While this cognitive deterioration is widespread, the mechanisms underlying dementia, its
underlying neuropathology, and why some individuals are vulnerable while others are resilient are poorly
understood. With advancing age, disruptions to circadian rhythms are virtually universal and precede age-related
dementia by as much as 15 years. Likewise, the blood-brain barrier (BBB) is regulated by circadian rhythms and
sleep, with disruptions to circadian timing/sleep leading to BBB dysfunction. Because deficits in BBB permeability
are linked to age-related cognitive deterioration, our proposal explores the possibility that age-related deficits in
circadian rhythms and resulting disturbances to sleep lead to BBB degradation and cognitive decline, and that
resilience to circadian degradation is neuroprotective. We will also apply a novel, non-invasive technology
developed by our group to rescue degraded circadian rhythms, BBB integrity, and cognition in aged vulnerable
animals that has broad translational applicability if successful. This technology is based on recent findings that
flickering gamma (40 Hz) lighting rescues circadian rhythms, cognitive function, and neuropathology in mouse
models of Alzheimer’s disease. Because flickering light of this frequency can cause discomfort, migraines, and
fatigue, we developed lighting using ‘masked’ 40-Hz spectral flicker (i.e., Invisible Spectral Flicker (ISF)) by
applying an antiphase color mixing approach that raises the critical frequency at which flicker is perceived. Our
pilot data reveal that this lighting generates 40 Hz oscillations in the brain comparable to 40 Hz flicker and
rescues circadian rhythms in behavior in aged animals. 40 Hz lighting treatment has not been applied to age-
associated cognitive decline of non-Alzheimer’s origin or BBB integrity with aging. The present proposal asks
two main questions: 1) Is vulnerability to circadian degradation with advancing age associated with cognitive
decline through deterioration of the BBB and resulting neuroinflammation, with mice resilient to age-related
circadian degradation resistant to BBBd and cognitive decline, and 2) Can non-invasive 40 Hz ISF lighting
treatment rescue circadian degradation and age-associated degradation of the BBB and cognitive functioning in
vulnerable mice? Together, these findings will enhance our understanding of the mechanisms and underlying
neuropathology of age-related cognitive decline, but also have the potential for wide-ranging treatment.

## Key facts

- **NIH application ID:** 10681091
- **Project number:** 1R21AG082436-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Daniela KAUFER
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $228,137
- **Award type:** 1
- **Project period:** 2023-06-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10681091

## Citation

> US National Institutes of Health, RePORTER application 10681091, Non-invasive lighting treatment as a novel therapeutic for age-related cognitive decline (1R21AG082436-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10681091. Licensed CC0.

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