Previous studies on mediation analysis of APOE have focused on mediators of cerebral blood flow [43], brain tissue volume [44], and neuropathological pathways [45], suggesting these factors partially mediated the negative effect of APOE4. When considering lipids as mediators, one study found that total cholesterol negatively mediated the effect of APOE2 on cognition [15]; another study found no lipids but BMI significantly mediated the risk of AD [16]. The gene discussed is APOE; the disease is Alzheimer disease.