Mediation analysis of the effect of depression on Alzheimer's disease risk in older adults

Music City Center 

Depression and Alzheimer's Disease (AD) are both highly prevalent among older adults, yet the causal relationship between them remains underexplored. Using datasets from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study, we examine whether geriatric depression has a significant causal effect on the risk of AD and investigate the mediating role of key biological and clinical mediators. To estimate these causal effects consistently, we control for ultra-high-dimensional potential confounders, including DNA methylation levels, applying a ball correlation-based method for confounder selection within the mediation analysis. To ensure robustness against model misspecification, we adopt a robust mediation analysis framework. Our findings indicate a significantly positive causal effect of geriatric depression on AD risk. Based on these insights, new prevention and treatment strategies for geriatric depression and Alzheimer's disease can be proposed by targeting the identified confounders and mediators.

mediation analysis

geriatric depression

Alzheimer's disease

causal inference

DNA methylation 

Biometrics Section