Previous studies have shown that the effect of the APOE gene on the risk of cognitive decline and dementia was modified by other genetic factors, including ABCA7 [7], SORL1 [21, 24], PICALM [25], CR1 [26], BIN1 [16], and TREM2 [27], showing complex gene-gene interactions [28]. The gene discussed is PICALM; the disease is dementia.