Specifically, p-tau181, p-tau217, and p-tau231 were detected by collecting plasma and CSF to describe the development of cognitive impairment and even AD (Janelidze et al. 2020; Ossenkoppele et al. 2022; Palmqvist et al. 2020; Thijssen et al. 2021); the levels of insulin and c-peptide in plasma and CSF would be measured to characterize the central and peripheral insulin promoted by Ex-4; and cognitive and mental state of the subjects would be measured by a scale, and cognitive decline/impairment was sub-categorized according to the diagnostic criteria (Beeri et al. 2014). The gene discussed is INS; the disease is Cognitive impairment.