# One-Year Follow-Up Cognitive Decline After Hip Fracture Surgery: The Prognostic Role of NSE and S100B Biomarkers in Elderly Patients, a Multicentric Study

## TL;DR

This study finds that elevated NSE and S100B biomarker levels at one year after hip surgery correlate with long-term cognitive decline in elderly patients.

## Contribution

The study is the first to show a link between NSE and S100B levels at one-year follow-up and chronic cognitive decline after hip surgery.

## Key findings

- NSE and S100B levels were significantly higher in patients with long-term cognitive decline at one year.
- Older age, diabetes, and lower baseline cognition were significant risk factors for long-term cognitive decline.
- Early postoperative POCD was not associated with elevated biomarker levels.

## Abstract

Background: Postoperative cognitive dysfunction (POCD) is a prevalent complication in elderly patients undergoing hip fracture surgery, often resulting in increased morbidity and prolonged rehabilitation. Biomarkers such as Neuron-Specific Enolase (NSE) and S100B protein have shown potential in detecting cerebral injury, yet their role in predicting long-term cognitive decline remains unclear. This study aimed to evaluate the association between biomarkers serum levels and the incidence of POCD in elderly patients undergoing proximal femur fracture surgery. Methods: A multicentric prospective observational study was conducted from January 2023 to February 2024, including 146 elderly patients with hip fractures treated surgically at ASL Bari and the University Orthopedic Department of Foggia. Biomarker levels of NSE and S100B were measured preoperatively (T0), at three days post-surgery (T1), and at one-year follow-up (T2). Cognitive function was assessed using the Pfeiffer Scale (PS) and the Mini-Mental State Examination (MMSE). Statistical analysis was performed using U Mann–Whitney tests and logistic regression to identify risk factors. Results: At three days post-surgery, 20.5% of patients exhibited POCD, with no significant differences in NSE and S100B levels compared to baseline. However, at one year, of the 96 patients investigated 37.9% of patients showed cognitive decline, with significantly elevated NSE (19.88 ± 4.03 μg/L) and S100B (1.86 ± 0.9 μg/L) compared to non-POCD patients (p = 0.01). Risk factors for long-term POCD included older age (OR: 1.24), diabetes mellitus (OR: 4.41), and lower baseline cognitive function (MMSE and PS scores, OR: 0.25 and 9.81, respectively). Conclusions: The study demonstrates that while early POCD is not associated with significant changes in NSE and S100B levels, their elevation at one-year follow-up suggests a possible correlation with chronic neuroinflammation and persistent neuronal damage. Preoperative cognitive impairment, advanced age, and diabetes mellitus are significant predictors of long-term cognitive decline. Incorporating biomarker evaluation and cognitive screening into perioperative management may enhance patient outcomes following hip fracture surgery.