1. Scientific Rationale
Cognitive decline, including mild cognitive impairment and dementia, presents a major global public health challenge. With aging populations, identifying etiological factors is crucial for developing preventive and therapeutic strategies. Poor sleep is linked to accelerated biological aging and higher risk of cognitive decline. Behaviors such as snoring, chronotype, daytime sleepiness, sleep duration, insomnia, and difficulty waking are associated with biological age acceleration. Long-term exposure to air pollutants is associated with increased cognitive impairment risk. Mechanisms may involve inflammation, oxidative stress, and other pathways affecting brain health. Plasma proteomics provides a molecular-level understanding of disease processes. It can identify biomarkers linking pathogenic risk factors to cognitive decline, offering insight into underlying biological pathways. However, there is currently no study that has analyzed the association between sleep and air pollution with cognitive decline through proteomics.
2. Research Questions
(1) How does sleep quality affect cognitive decline, assessed via brain disorders, imaging, and cognitive tests? (2) What is the effect of long-term ambient air pollution exposure on cognitive decline across these dimensions? (3) Do plasma proteomic profiles mediate the relationship between sleep quality and cognitive decline? (4) Is there an interaction between sleep quality and air pollution in influencing cognitive decline, potentially via proteomic mediators?
3. Research Objectives
(1) Assess associations between sleep behaviors and cognitive decline using UK Biobank data. (2) Evaluate the impact of long-term air pollution exposure on brain disorders, imaging, and cognitive outcomes. (3) Identify proteins mediating the effects of sleep and air pollution on cognitive decline. (4) Explore interaction effects between poor sleep and high pollution exposure, focusing on proteomic pathways.
