Exploring Sex-Related Difference in Cerebrospinal Fluid/Blood Quotient of Albumin in Older Patients Undergoing Hip Fracture Surgery: Insight From the ORTODEL and BIODEL Study

Background: The blood-cerebrospinal fluid barrier (BCSFB) regulates substance exchange between the blood and cerebrospinal fluid (CSF). Objectives: This study investigated sex-related differences in the CSF/blood quotient of albumin (QAlb), a BCSFB function biomarker, in older patients undergoing spinal anesthesia for hip fracture (HF) surgery. Design: Seventy-eight patients aged ≥ 65 years (18 males, 60 females) undergoing HF repair were enrolled. Methods: Baseline variables, including age, sex, diagnosis of dementia, were collected. The BCSFB function was assessed using the CSF/blood quotient of albumin (QAlb). Results: Dementia prevalence was similar in men (22.2%) and women (17.6%), as was postoperative delirium (POD) (men 27.8%, women 33.3%). Despite similar demographics, men exhibited significantly higher CSF albumin concentrations (p=0.031) and QAlb values (p=0.023) compared to women. No differences were found in QAlb value between patients with or without dementia in male (p=0.645) and female (p=0.102) subgroups. Moreover, no differences in QAlb value emerged between those with or without POD in males (p=0.173) and females (p=0.225). Conclusion: Despite sample size and sex imbalance, our analyses highlight a sex-related discrepancy in BCSFB function in older patients underscoring the need for sex-specific QAlb reference ranges. Normalization of QAlb values by sex may be essential to prevent over- or underestimation of BCSFB dysfunction in the two sexes. Future studies with larger, balanced cohorts may clarify these differences.