To determine the sex-divergent effects of ApoE4 and metformin on cognitive, anxiety-like, and depression-like phenotype in aged mice, male and female apoE3-TR or apoE4-TR mice, were gavaged with metformin from 13 months old to 18months old, and their behavioral manifestation assessed using MWM, EPM, OFT, TST, FST. The gene discussed is APOE; the disease is major depressive disorder.