However, after adjusting for baseline sex, education, ApoE ε4 status, and time-varying covariates of age, BMI, alcohol use, smoking, physical activity score, diabetes, hypertension, stroke, PPI use, depression medication and antibiotic use, and Mediterranean diet score, the association between laxative use with a change in GCS over 13 years of follow-up was attenuated (laxative use∗time β = 0.006; Padj=0.28) (Figure 4). This evidence concerns the gene APOE and major depressive disorder.