A Pilot Study of Digital Sleep Optimization for Brain Health Outcomes in Older Surgical Patients (SLEEP-BOOST)

The primary goal of this randomized controlled trial is to test the feasibility and acceptability of preoperative sleep optimization (CBT-I) in orthopedic patients with moderate/severe insomnia. Secondary outcomes include cognitive, pain, and function.
- Sponsor: National Institute on Aging
- PI: Lei Gao, M.B.B.S., M.M.Sc.
- Co-I: Peng Li, Ph.D.; John Winkelman, M.D., Ph.D.
The figure above shows conceptual pathways linking sleep optimization, cognitive resilience, and brain health outcomes after surgery. NCD neurocognitive disorder; POD postoperative delirium; LOS length of stay. dCBT-I preoperative digital cognitive behavioral therapy for insomnia (hygiene, stimulus control, relaxation tools, cognitive restructuring). Feasibility results (Aim 1) will guide protocol adjustments and efficacy (Aim 2).
Sleep/Circadian Regulation and Progression to Postoperative Dementia
The goal of this grant is to test whether sleep/circadian regulation is associated with postoperative cognitive disorders, including delirium (POD), and progression to dementia within 12 months. It also tests whether the relationship is affected by AD genetic risk and AD pathology (plasma tau and amyloid).
- Sponsor: Alzheimer’s Association
- PI: Lei Gao, M.B.B.S., M.M.Sc.

The SCOPE Trial: Sleep, Cognition, and Pain Bundle vs. ERAS-Cardiac for Postoperative Delirium


The goal of this multisite randomized controlled trial is to test whether preoperative sleep optimization with cognitive behavioral therapy for insomnia, cognitive (brain puzzle) training, and scheduled intravenous acetaminophen use over 48 hours is superior to the current Enhanced Recovery (ERAS) for Cardiac Surgery protocol in the prevention of postoperative delirium (POD). Responsible for the overall study and specifically will lead the sleep CBT-I intervention and Chair of the Digital Technology Committee.
- Sponsor: Patient-Centered Outcomes Research Institute (PCORI)
- Co-PIs: Lei Gao, M.B.B.S., M.M.Sc.; Balachundhar Subramaniam, M.D., M.PH, FASA
Multisite randomized controlled trail that will enroll 406 patients undergoing cardiac surgery to test whether a novel sleep optimization, cognition prehabilitation, and analgesia bundle is superior to established ERAS (enhanced recovery after surgery) standard of care protocols (figure below).

Circadian Multiscale Activity Regulation and the Risk for Delirium in Elderly Hospitalized Patients
As part of the Grants for Early Medical/Surgical Specialists’ Transition to Aging Research (GEMSSTAR) award, this project aims to determine whether the multiscale regulation of motor activity can be a sensitive biomarker of delirium in the elderly.

- Sponsor: National Institute on Aging
- PI: Lei Gao, M.B.B.S., M.M.Sc.
Circadian regulation, autonomic function, and Alzheimer’s disease

This project is designed to determine whether changes in circadian regulation and autonomic function can predict the development and progression of AD and cognitive decline in the elderly people at early, preclinical stages. This project may provide new intervention targets in future clinical studies of AD, and can lay the groundwork for the design of novel unobtrusive, cost-efficient tools for long-term monitoring of cognitive impairment or risk for AD.
- Sponsor: BrightFocus Foundation
- PI: Peng Li, Ph.D.
- Co-PI: Lei Gao, MBBS; Kun Hu, Ph.D.
Timing and irregularity of daytime napping and Alzheimer’s disease
Longer and more frequent daytime naps were associated with higher risk of AD. More excessive (longer or more frequent) daytime napping was correlated with worse cognition, and conversely, worse cognition was correlated with more excessive naps. Older adults also nap irregularly and at different times of the day. Are these napping characteristics (i.e., timing and regularity) associated with cognitive decline or risk of AD?
- Sponsor: Alzheimer’s Association
- PI: Chenlu Gao, Ph.D.
- Mentor: Peng Li, Ph.D.; Kun Hu, Ph.D.; David A Bennet, Ph.D.

Daytime napping and Alzheimer’s disease in middle-to-older aged adults: Timing, irregularity, and interaction with genetic risks

This project will test whether actigraphy-measured napping is cross-sectionally associated with cognition and prospectively associated with incident dementia/AD in a sample of ~99,000 middle- to older-aged participants. Findings will improve the understanding of risk factors for cognitive impairments in the aging population and help identify people at elevated risks of dementia at early stages.
- Sponsor: American Academy of Sleep Medicine Foundation
- PI: Chenlu Gao, Ph.D.
- Mentor: Peng Li, Ph.D.; Kun Hu, Ph.D.; David A Bennet, Ph.D.
Integrative Motor Activity Biomarker for the Risk of Alzheimer’s Risk

Many non-cognitive physiological changes including reduced physical activity, sleep and circadian disturbances, and degraded fractal regulation predict the risk of Alzheimer’s disease (AD), and they can be assessed unobtrusively from daily spontaneous motor activity. Adopting a novel artificial intelligence approach, this project is proposed to develop an integrated biomarker for AD risk in older adults by combining these physiological functions, and to examine the relationships of this biomarker with genetics and AD pathology. This project will potentially provide a non-invasive tool for predicting AD risk and lead unique insights into the complex pathology of AD, which is important for developing new therapeutic strategies to treat AD or slow down AD progression.
- Sponsor: National Institute on Aging
- PI: Kun Hu, Ph.D.
- Co-I: Richa Saxena, Ph.D.
Circadian Disturbance and Dementia in Latin America (ReDLat)
Almost all biological/physiological processes such as sleep and physical activity levels display circadian rhythms (of ~24 h) that are regulated by the endogenous circadian system, and disrupted circadian rhythms are linked to many adverse health outcomes including increased risk for sleep disorders, cardiometabolic diseases, and dementia. Using the existing cohort of ReDLat (Multi-Partner Consortium to Expand Dementia Research in Latin America) and an unobtrusive assessment of circadian health, this project is proposed to examine the effects of age, sex, and socioeconomic factors on circadian function in Latinos, and the involvement of circadian disturbance in the characterization of two types of dementias (Alzheimer’s disease and frontotemporal lobar degeneration) in this underrepresented population. The project will help address Latino health disparities, provide a sustainable, scalable and equitable approach to circadian health monitoring and a non-invasive tool for assessment or identification of dementia, and lead insights into the relevance of circadian disturbance to the high and increasing prevalence of dementia in Latin American countries.
- Sponsor: Alzheimer’s Association
- PI: Kun Hu, Ph.D.
- Co-i: Peng Li, Ph.D.; Lei Gao, M.B.B.S.; Jacqueline M. Lane, Ph.D.

Alzheimer’s Disease

Circadian regulation, autonomic function, and Alzheimer’s disease
This project is designed to determine whether changes in circadian regulation and autonomic function can predict the development and progression of AD and cognitive decline in the elderly people at early, preclinical stages. This project may provide new intervention targets in future clinical studies of AD, and can lay the groundwork for the design of novel unobtrusive, cost-efficient tools for long-term monitoring of cognitive impairment or risk for AD.
- Sponsor: BrightFocus Foundation
- PI: Peng Li, Ph.D.
- Co-PI: Lei Gao, MBBS; Kun Hu, Ph.D.
Timing and irregularity of daytime napping and Alzheimer’s disease
Longer and more frequent daytime naps were associated with higher risk of AD. More excessive (longer or more frequent) daytime napping was correlated with worse cognition, and conversely, worse cognition was correlated with more excessive naps. Older adults also nap irregularly and at different times of the day. Are these napping characteristics (i.e., timing and regularity) associated with cognitive decline or risk of AD?
- ponsor: Alzheimer’s Association
- PI: Chenlu Gao, Ph.D.
- Mentor: Peng Li, Ph.D.; Kun Hu, Ph.D.; David A Bennet, Ph.D.


Daytime napping and Alzheimer’s disease in middle-to-older aged adults: Timing, irregularity, and interaction with genetic risks
This project will test whether actigraphy-measured napping is cross-sectionally associated with cognition and prospectively associated with incident dementia/AD in a sample of ~99,000 middle- to older-aged participants. Findings will improve the understanding of risk factors for cognitive impairments in the aging population and help identify people at elevated risks of dementia at early stages.
- Sponsor: American Academy of Sleep Medicine Foundation
- PI: Chenlu Gao, Ph.D.
- Mentor: Peng Li, Ph.D.; Kun Hu, Ph.D.; David A Bennet, Ph.D.