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 (e2e2, e2e3, e2e4, e3e3, e3e4, and e4e4) 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: APOE2 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 APOE4 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.