We replicated a mouse model of dyslipidemia and postmenopausal status in LDLR−/− mice and treated them with β-estradiol or simvastatin, and found that ovariectomy in LDLR−/− mice led to an exacerbation of dyslipidemia and increased hippocampal apoptosis and cognitive impairment, which were associated with reduced estradiol levels and ERα, ERβ and GPER expression. Here, ESR1 is linked to Cognitive impairment.