Association of insulin resistance with delirium and CSF biomarkers of Alzheimer's disease in elderly patients with hip fracture

BackgroundDelirium is associated with dementia, which shares symptoms of cognitive dysfunctions. Notably, pathological mechanisms of Alzheimer's disease (AD) appear involved in both conditions. Insulin resistance has been reported to be a risk factor for AD, leading to neurodegeneration and cognitive impairment by affecting amyloid-beta (A beta) metabolism, tau phosphorylation, and neuro-inflammation. Thus, insulin resistance may provide pathophysiological clues to the occurrence of delirium.AimTo investigate the relationship between preoperative insulin resistance, insulin concentrations in the cerebrospinal fluid (CSF), and delirium in elderly patients with hip fracture.MethodsThe study included 138 elderly patients with or without pre-existing dementia who underwent hip fracture surgery. Delirium was diagnosed with the confusion assessment method performed daily from pre-operation to 5 days post-operation. CSF and blood samples were collected at the beginning of spinal anesthesia. The concentrations of insulin, amyloid-beta1-42 (A beta 42), total tau (t-tau), and phosphorylated tau (p-tau)(181) were determined by ELISA. Homeostasis model assessment (HOMA-IR) was used to assess insulin resistance.ResultsSixty-one (44%) of 138 hip fracture patients developed delirium peri-operatively. Compared to non-delirium group, the preoperative HOMA-IR index in delirium was much higher (median 3.3 vs 2.8, p = 0.001), but the CSF insulin concentration was significantly decreased (median 1.5 vs 2.2 mU/L, p < 0.001). Binary logistic regression analysis showed that HOMA-IR index and CSF insulin concentration were independent risk factors for delirium (p < 0.05). HOMA-IR index was negatively correlated with CSF insulin concentrations (rho = - 0.55, p < 0.001). Multiple linear regression analysis showed that AD core biomarkers were significantly correlated with HOMA-IR index and CSF insulin level (p < 0.05).ConclusionThis study innovatively examined insulin concentrations in serum and cerebrospinal fluid in patients with delirium. Our findings suggest that preoperative insulin resistance may affect the occurrence of delirium. The potential association between insulin resistance and delirium may be related to insulin resistance affecting the metabolism of AD biomarkers.

Automated summary

This study examined the relationship between preoperative insulin resistance, insulin concentrations in the cerebrospinal fluid (CSF), and delirium in elderly patients with hip fracture. The study found that patients with higher preoperative insulin resistance were more likely to develop delirium, while the concentrations of insulin in the CSF were significantly decreased. Insulin resistance may affect the occurrence of delirium by affecting the metabolism of AD biomarkers.