1. Research Questions:
This study aims to explore the association between sleep, cognitive function, related biomarkers, and mortality outcomes.
2. Objectives:
Using multidimensional sleep parameters obtained from self-reports, accelerometer measurements, and sleep-related diagnoses from medical records, this study will systematically evaluate the longitudinal relationship between sleep, cognitive decline, and mortality.
3. Scientific Rationale:
3.1 Exposure Variables: 1) Objective sleep parameters, including sleep duration, sleep onset time, sleep efficiency, sleep fragmentation, and calculated rest-activity rhythm parameters, will be obtained from multi-day wrist accelerometer data. 2) Subjective sleep patterns will be assessed using validated sleep questionnaires and self-reports. 3) Sleep disorder diagnoses (ICD codes) and sleep medication usage will be extracted from participants’ medical records.
3.2 Outcome Variables:
Cognitive decline will be evaluated using longitudinal cognitive function test scores. Medical records will provide diagnoses and treatment records related to cognitive impairment and mortality. Additionally, longitudinal neuroimaging data, related fluid biomarkers, polygenic risk scores for cognition, and multidimensional cognitive outcome parameters will be incorporated.
3.3 Analytical Methods:
A sleep-related longitudinal cohort will be established, and cox proportional hazards regression models and survival analyses will be constructed to assess the impact of multidimensional sleep parameters on cognitive decline and mortality events. Sensitivity analyses will be conducted across subgroups, including different age groups, sex, sleep disorder history, family history of dementia, and APOE-4 allele carriers. Additionally, linear regression models will be used to investigate associations between sleep parameters, fluid and imaging biomarkers. Analyses will be conducted using R and Python.
