Pregnancy complications (e.g. preeclampsia) may set a trajectory for poorer brain health.166 Parity (number of children) history influences APOE4’s effects on the brain and cognition,167 and use of hormonal contraception has been associated with reduced cognitive impairment and reduced dementia risk.28 Although pregnancy and hormonal contraception use may occur decades before menopause, the substantial ovarian hormone changes during these periods may result in lasting brain changes that influence an individual’s response to MHT (see Box 1 below). The gene discussed is APOE; the disease is preeclampsia.