# Lifecourse sleep, cognitive decline and risk of Alzheimer's disease: a pooled cohort study.

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $729,553

## Abstract

PROJECT SUMMARY/ABSTRACT
Mounting evidence from our team and others suggests a potential bi-directional relationship between sleep and
Alzheimer's disease and related dementias (ADRD) in older adults, in which sleep disturbances precede clinical
ADRD, in addition to commonly occurring after disease onset. This bi-directional relationship has important
implications for the early intervention of ADRD, yet it remains debatable whether sleep disturbance is a prodromal
or modifiable risk factor of ADRD. Research to disentangle the role of sleep in ADRD requires the use of a life
course approach to address the directionality of the association, particularly given the long neurodegenerative
processes leading to ADRD before symptoms onset and the large variations in sleep disturbances across the
life course. Our long-term goal is to develop preventive strategies for ADRD by addressing the role of sleep
disturbances across the life course. The objective of this proposal is to determine the effects of objective and
subjective sleep disturbances on age-related cognitive decline and risk of ADRD across the life course in diverse
populations, and to elucidate mechanistic pathways contributing to this association at different stages of life. Our
central hypothesis is that objective and subjective sleep disturbances over the life course are associated with
life-course cognitive trajectories and risk of ADRD, with varying magnitude and different underlying pathways for
each stage of life. We have an unprecedented opportunity to leverage data from six well-characterized
longitudinal cohorts, two with 40-50% Black or Mexican American participants, to create a synthesized diverse
cohort of ~35,000 (age 30-104) adults with objective (polysomnography and actigraphy) and subjective sleep
measures, and cognition assessed regularly spanning up to 60 years. We will also perform replication analysis
using data from the UK Biobank, a study of 500,000 UK adults aged 40-84 years. By applying an innovative life
course approach both in the synthesized and each individual cohort, we will address the following aims: 1)
Identify age trends in objective and subjective sleep disturbances and cognition from early adulthood to the
oldest old; 2) Evaluate the longitudinal association between sleep disturbances at different stages of life and
cognitive performance over the life course including incident ADRD; 3) Elucidate and compare novel pathways
linking sleep disturbances to ADRD at different stages of life. The research is highly significant because it helps
to address the timing of sleep disturbances in relation to cognitive aging over the life course and thus the
directionality of the relationship. The creation of the first-ever synthesized diverse cohort of sleep and cognition
across the life course will also develop foundational resources for future research to disentangle the bi-directional
link between sleep and ADRD. This work has a large impact as a critical step towards el...

## Key facts

- **NIH application ID:** 10885684
- **Project number:** 1R01AG083836-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Yue Leng
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $729,553
- **Award type:** 1
- **Project period:** 2024-05-15 → 2029-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10885684

## Citation

> US National Institutes of Health, RePORTER application 10885684, Lifecourse sleep, cognitive decline and risk of Alzheimer's disease: a pooled cohort study. (1R01AG083836-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10885684. Licensed CC0.

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