The working mechanism for microglia regulation of LTP activity and cognitive function has been established in the literature.[34] Activation of microglia produces IL‐1β and TNFα, which impairs induction of LTP and memory performance by preventing AMPA receptor GluR1 subunit phosphorylation.[48] Therefore, we propose that hippocampal E4bp4 coordinates circadian clock regulation of delirium‐associated cognitive decline, explaining why circadian disruption (e.g., a problem commonly shared by ICU and elderly patients) promotes the occurrence of delirium. This evidence concerns the gene CLOCK and delirium.