PROJECT SUMMARY/ABSTRACT Poor sleep is associated with decreased memory functioning in older adults, including those with mild cognitive impairment (MCI) and Alzheimer’s disease (AD) and related dementias (ADRD), which diminishes sleep’s critical contribution to cognitive processing and memory in healthy and pathological aging. Our team has developed an effective lighting intervention therapy (LIT) for improving sleep and behavioral outcomes in ADRD patients living in nursing homes, but the mechanisms by which LIT works in the brain are not completely understood. To understand the mechanisms by which LIT benefits these patients, a sensitive and precise tool is required to detect and measure changes in the volumes, connectivity, and function of key brain regions. The current application proposes to use high-resolution multi-modal 7T imaging to investigate the impact of LIT on sleep physiology and brain structure, function, and connectivity in MCI and mild AD patients. This technique will enable us to produce exceptionally high-resolution, high-contrast images that reveal subtle structural and functional abnormalities that are below the detectability threshold of conventional MRI. Through the study’s 2 aims, we will test the following hypotheses: 1) LIT will induce measurable effects on brain regions and circuits associated with AD pathology; 2) LIT will improve sleep quantity and quality, cognition, mood, and quality of life compared to controls; 3) these improvements will correlate with quantitative difference measurements; and 4) LIT will show reduced effects on brain structures compared to control. Aim 1 will comprise a longitudinal crossover 7T imaging study applying the active and control LITs on a group of 25 patients with MCI or mild AD along with an optimized multi-modal 7T imaging protocol designed to capture the anatomy involved in AD pathophysiology and light exposure, measuring the LIT’s effect on sleep and cognition. Aim 2 will analyze correlations between the pre- and post-active and control lighting interventions’ differences in quantitative imaging measures (regional volumes, functional and diffusion connectivity, and graph theory metrics) and PET, sleep (actigraphy) and neuropsychological measures. This is the first application of imaging to track the effect of LIT in MCI and mild AD. We plan to apply 7T imaging to provide a highly sensitive window into the degree to which LIT may improve sleep and cognition and potentially delay disease progression and improve quality of life for patients with MCI and AD.