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).

Insulin resistance and osteocalcin associate with the incidence and severity of postoperative delirium in elderly patients undergoing joint replacement.

AIM: While insulin sensitivity plays an important role in maintaining glucose metabolic homeostasis and cognitive function, its impact on postoperative delirium (POD) remains unclear. This study aimed to investigate the association between POD and indicators of insulin sensitivity, including insulin resistance and osteocalcin. METHODS: A total of 120 elderly patients undergoing joint replacement were recruited and divided into delirium and non-delirium groups. Plasma and cerebrospinal fluid (CSF) samples were collected for the analysis of biomarkers, including insulin, uncarboxylated osteocalcin (ucOC), total osteocalcin (tOC), and glucose. Insulin resistance was assessed through the homeostatic model assessment of insulin resistance (HOMA-IR). MAIN RESULTS: Out of the total, 28 patients (23.3%) experienced POD within 5 days after surgery. Patients with delirium exhibited higher levels of preoperative HOMA-IR and ucOC in CSF and plasma, and of tOC in CSF (P = 0.028, P < 0.001, P = 0.005, P = 0.019). After adjusting for variables, including age, Mini-Mental State Examination score, surgical site and preoperative fracture, only preoperative ucOC in CSF and HOMA-IR were significantly linked to the incidence of delirium (OR = 5.940, P = 0.008; OR = 1.208, P = 0.046, respectively), both of which also correlated with the severity of delirium (P = 0.007, P < 0.001). Receiver operating curve analysis indicated that preoperative HOMA-IR and ucOC in CSF might partly predict POD (area under the curve [AUC] = 0.697, 95% confidence interval [CI] = 0.501-0.775, AUC = 0.745, 95% CI = 0.659-0.860). CONCLUSIONS: We observed that preoperative elevated HOMA-IR and ucOC in CSF were associated with the incidence and severity of POD. While these preliminary results need confirmation, they suggest a potential involvement of insulin resistance and osteocalcin in the pathological mechanism of POD. Geriatr Gerontol Int 2024; 24: 421-429.

BIS-guided deep anesthesia decreases short-term postoperative cognitive dysfunction and peripheral inflammation in elderly patients undergoing abdominal surgery.

OBJECTIVES: Postoperative cognitive dysfunction (POCD) is a common clinical complication, with an underlying pathophysiology linked to heightened levels of neuroinflammation. However, it requires clarification as to whether the depth of anesthesia modulates postoperative cognitive dysfunction. This study investigated the association between depth of anesthesia and POCD in elderly patients undergoing abdominal surgery. METHODS: A total of 120 patients aged 60 years or older who were planned for abdominal surgery under total intravenous anesthesia were included in this study. The depth of anesthesia was guided by monitoring Bispectral Index (BIS) data. All study participants completed a battery of nine neuropsychological tests before surgery and at 7 days and 3 months after surgery. POCD was calculated by using the reliable change index. Plasma concentration of C-reactive protein (CRP), interleukin (IL)-1ß, IL-10, S-100ß, and norepinephrine (NE) were measured. RESULTS: The incidence of POCD at 7 days after surgery in the deep anesthesia group was 19.2% (10/52), which was significantly lower (p = 0.032) than the light anesthesia group 39.6% (21/53). The depth of anesthesia had no effect on POCD at 3 months after surgery (10.3% vs 14.6%, respectively, p = 0.558). Similarly, plasma levels of CRP and IL-1ß in deep anesthesia group were lower than that in light anesthesia group at 7 days after surgery (p < 0.05), but not at 3 months after surgery (p > 0.05). There were no significant differences in the plasma concentration of IL-10, S-100ß, and NE between the groups (p > 0.05). CONCLUSIONS: Deep anesthesia under total intravenous anesthesia could decrease the occurrence of short-term POCD and inhibit postoperative peripheral inflammation in elderly patients undergoing abdominal surgery, compared with light anesthesia.