Biological pathways linking sleep health to Alzheimers disease and cognitive decline

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.