The underlying mechanism may be related to the activation of apoptosis signal-regulating kinase 1 (ASK-1) [ASK has been shown to be closely related to cognitive impairment caused by chronic hypoperfusion (Toyama et al., 2014)], inhibition of PI3K/Akt/Nrf2/Heme Oxygenase-1 (HO-1) signaling, and the upregulation of COX-2; all these may eventually lead to neuronal apoptosis (Cheon et al., 2016). This evidence concerns the gene MAP3K5 and Cognitive impairment.