Protective effect of intranasal insulin on postoperative cognitive dysfunction in elderly patients with metabolic syndrome undergoing noncardiac surgery: a randomized clinical trial

Background Insulin plays a crucial and multifactorial role in cognitive activity, with insulin resistance appearing in neurodegenerative and metabolic diseases. Insulin resistance contributes to the pathobiology of postoperative cognitive dysfunction (POCD) in experimental models, which can be rescued by intranasal insulin administration. Aims To test the effect of intranasal insulin on the incidence of POCD in elderly patients with metabolic syndrome. Methods The study was designed as a randomized, double-blind, placebo-controlled clinical trial. 116 elderly participants were randomly assigned to receive either 40 IU insulin ( n = 58) or placebo ( n = 58) for 7 days. The primary outcome was the incidence of POCD at 7 days and 3 months after surgery. Secondary outcomes included the degree of peripheral insulin resistance postoperatively, changes in peripheral inflammation levels and the safety of interventions. Results The results showed that POCD occurred in the insulin group on the 7th postoperative day in 11 (20.8%) patients, which was fewer than the 23 (45.1%) patients in the placebo group ( P = 0.008). The insulin group indicated better cognitive functional performance on language and memory test than the placebo group ( P < 0.05). Mean peripheral plasma concentration of TNF-α ( P < 0.05) and CRP ( P < 0.001) in the insulin group was significantly declined compared with the placebo group on D3 and D7. Conclusions Intranasal insulin administration reduced the incidence of POCD and alleviated peripheral inflammatory levels in elderly patients with metabolic syndrome. Trial registry Chinese Clinical Trial Registry (ChiCTR1800015502).