Insulin Resistance, AD Pathology and Delirium

Delirium, a common condition among elderly hospitalized patients, is associated with serious consequences and remains poorly understood with no specific treatment available. Recent studies have identified a close connection between delirium and dementia, with certain Alzheimer's disease biomarkers found in delirious patients. Insulin resistance, which affects the metabolism of these biomarkers, has been suggested as a potential trigger for neurodegenerative changes, prompting researchers to explore its association with delirium in elderly patients with hip fracture. Their findings revealed that delirium patients exhibited higher insulin resistance and lower cerebrospinal fluid insulin levels, particularly in those with dementia, highlighting the potential link between insulin resistance and delirium.

Delirium, characterized by sudden confusion and mental status changes, is a common condition observed in elderly hospitalized patients. This condition can have serious consequences, including decreased functioning, extended hospital stays, increased complications, and even death. Unfortunately, the causes and mechanisms of delirium remain poorly understood, and there is currently no specific treatment available. Recent studies have shown a close association between delirium and dementia, with certain biomarkers associated with Alzheimer's disease (AD) being found in delirious patients. Additionally, hyperinsulinemia or insulin resistance (IR), which affects the metabolism of these biomarkers, has been suggested as a potential trigger for neurodegenerative changes in AD.

Insulin's role in the brain

Originally known for its role in regulating peripheral metabolism, insulin has been found to play unique functions in the brain. Various regions of the brain important for cognitive function contain insulin receptors. Insulin regulates crucial processes such as neuronal survival, gene expression, synaptic viability, and neurotransmitter release. It also influences the clearance of AD-related biomarkers, affects vascular function, lipid metabolism, and inflammation. In neurodegenerative diseases, including AD, IR has been associated with decreased expression of insulin receptors and the manifestation of brain abnormalities observed in these conditions.

Exploring the association between insulin resistance and delirium

While IR has been extensively studied in relation to neurodegenerative diseases, limited research has been conducted on its association with delirium. One study revealed that intranasal insulin administration reduced the incidence of postoperative delirium in elderly patients, potentially due to improved cerebral oxygenation and decreased inflammation. However, this study did not measure insulin levels in delirious patients or examine their relationship with AD biomarkers. Consequently, researchers aimed to investigate changes in insulin levels in the blood and cerebrospinal fluid (CSF) of hip fracture patients with delirium. Their objective was to explore the relationship between IR and delirium in elderly patients with hip fracture and determine whether AD pathology is a potential underlying mechanism linking insulin resistance and delirium.

Study design and findings

The study, registered with the Chinese Clinical Trial Registry and receiving ethical approval, involved elderly patients undergoing hip fracture repair. Patients with specific neurological diseases or conditions were excluded from the study. Various assessments and procedures were conducted throughout the study, including cognitive decline assessments, delirium evaluations, anesthesia and surgery details, and the collection of plasma and CSF samples. Insulin concentrations in both plasma and CSF, as well as AD biomarkers, were measured using enzyme-linked immunosorbent assay (ELISA). Insulin resistance was assessed using the homeostasis model assessment index (HOMA-IR).

A total of 138 hip fracture patients were included in the study, with an average age of 81.2 years and 63% of them being female. Among the patients, 44% experienced delirium, with 24% having preoperative delirium and 20% having postoperative delirium. Comparison between delirium and non-delirium patients revealed that delirium patients were older, less educated, more likely to have dementia, and had lower scores in cognitive assessment tools. Delirium patients also exhibited higher insulin resistance and lower CSF insulin levels compared to non-delirium patients. Stratified analysis based on dementia and delirium status demonstrated that delirium patients with dementia had the highest insulin resistance and lowest CSF insulin concentration, while patients without dementia or delirium had the lowest insulin resistance and highest CSF insulin concentration.

In conclusion, we found that in elderly patients undergoing surgery for traumatic hip fracture, the insulin resistance is closely related to the occurrence of delirium, which could possibly serve as a delirium risk indicator. However, this association was mainly seen in patients without pre-existing dementia.