# Biological pathways linking sleep health to Alzheimers disease and cognitive decline

> **NIH NIH K01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $129,249

## Abstract

Abstract/Summary
 The negative health outcomes associated with poor sleep health, including insufficient duration of sleep
and chronic insomnia, have been well documented. These outcomes include an elevated risk for cognitive
decline and Alzheimer’s disease. The combination of insomnia with short sleep duration may elevate the risk
for cognitive impairments and Alzheimer’s disease even further, given the growing literature linking this
particular insomnia phenotype with increased risk for cardiovascular disease and type 2 diabetes, both of
which have been linked to cognitive decline risk. However, the direct connection between biological pathways
disrupted in short sleep insomnia and Alzheimer’s disease is not well understood, and only limited
experimental sleep deprivation research has tried to identify changes in Alzheimer’s disease biomarkers
indicating neuronal degeneration. The current proposal seeks to address this gap in knowledge. With training
from, and collaborations with several experts in sleep research, biostatistical, multi-omics, metabolomics
analyses, and Alzheimer’s disease research, the applicant will gain the expertise needed to address these
questions. By utilizing an interdisciplinary approach incorporating complex data analytics, the project aims to
generate a broad range of independent research. The project has three main aims. In the first aim, we will use
a multi-omics approach analyzing both methylation and metabolomics data and the associated with short sleep
and insomnia, independently and interacting, among a high-risk Hispanic population. Then, we will compare
the results from aim 1 to previously identified methylation and metabolomics biomarkers for Alzheimer’s
disease to identify overlapping pathways. The second aim is to determine the direct relationship between
partial sleep deprivation and the presence of metabolites and blood-based Alzheimer’s disease biomarkers.
For this, we will use an experimental design, namely individuals undergoing a partial sleep deprivation
experiment, and analyze changes among these biomarkers using advanced bioinformatic tools to identify
underlying pathways. The final and third aim will integrate the results from the first aims and decipher the
causal effect of short sleep and insomnia on Alzheimer’s disease and then identify the mediating effects of the
biomarkers identified in the earlier projects. This study will be, by far, the largest study to date to utilize novel,
innovative multi-omics, and bioinformatics approaches to study short sleep insomnia. Addressing a critical
need, we will identify underlying biological pathways affected by insomnia and short sleep and characterize its
connection to Alzheimer’s disease and related neurodegenerative processes. This research can critically
inform future research on potential therapeutic targets, especially for a population with known health
disparities.

## Key facts

- **NIH application ID:** 10887078
- **Project number:** 1K01AG081542-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Cynthia Diana Johanna Kusters
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $129,249
- **Award type:** 1
- **Project period:** 2024-08-01 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10887078

## Citation

> US National Institutes of Health, RePORTER application 10887078, Biological pathways linking sleep health to Alzheimers disease and cognitive decline (1K01AG081542-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10887078. Licensed CC0.

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