NR3C1 and major depressive disorder: These findings are consistent with the “glucocorticoid cascade hypothesis,” which suggests that AD patients with cognitive deficits are associated with hypothalamus–pituitary–adrenal (HPA) axis dysfunction, as evidenced by increased glucocorticoid (GC) levels and abnormal glucocorticoid receptor (GR) expression (De Kloet et al., 2005; Xu et al., 2009), leading to emotional (depression or anxiety) and cognitive disorders at the late stage of AD.