Apolipoprotein E Induced Cognitive Dysfunction: Mediation Analysis of Lipids and Glucose Biomarkers in an Elderly Cohort Study

Introduction: Prior evidence suggested Apolipoprotein E (APOE), lipids, and glucose metabolism may act through the same pathways on the pathogenesis of Alzheimer's disease (AD). Methods: This prospective study used data from the Chinese Longitudinal Healthy Longevity Study. We tested the associations of APOE genotype (epsilon 2 epsilon 2, epsilon 2 epsilon 3, epsilon 2 epsilon 4, epsilon 3 epsilon 3, epsilon 3 epsilon 4, and epsilon 4 epsilon 4) and cognitive function using generalized estimating equations (GEE). We examined for possible mediation and effect modification by lipids and glucose level in this association. Results: APOE epsilon 2 showed significant direct protective effect and indirect harmful effect through TC on cognitive function. Abnormal lipids or glucose levels were not consistently associated with cognitive dysfunction in our study. We did not detect significant indirect effects through lipids for APOE epsilon 4 or any indirect effects through glucose. Discussion: These findings suggested complicated relationships among APOE, lipids, glucose, and cognitive function. Further study can make validations in other populations.

Automated summary

The study found complex relationships among APOE genotype, lipids, glucose, and cognitive function, with possible mediation or effect modification by lipids and glucose levels. However, abnormal lipids or glucose levels were not consistently associated with cognitive dysfunction in this study.