Effects of Biological Sex and Age on Cerebrospinal Fluid Markers-A Retrospective Observational Study.

OBJECTIVE

Cerebrospinal fluid (CSF) analysis is a key diagnostic tool for neurological diseases. To date, only a few studies have investigated in larger cohorts the effect of age and biological sex on diagnostic markers extracted from CSF.

METHODS

For this retrospective observational study, 4163 CSF findings (2012-2020) were evaluated. After exclusion of pathogenic CSF findings above or below the locally established reference ranges that are routinely applied in the CSF laboratory for clinical reporting, 1270 findings were included for statistical analysis. Using regression analysis, the relationship between age and CSF markers was illustrated, and regression equations were created.

RESULTS

A significant effect of sex was shown for CSF albumin (p < 0.001; ΔM 29.34), CSF protein (p < 0.001; ΔM 39.38) and CSF glucose (p < 0.001; ΔM 3.63) as well as CSF/serum albumin quotient (Q Alb) (p < 0.001; ΔM 0.57), for Immunoglobulin G in CSF (IgG CSF) (p < 0.001; ΔM 2.48), CSF/serum IgG quotient (Q IgG) (p < 0.001; ΔM 0.27), Immunoglobulin A in CSF (IgA CSF) (p < 0.001; ΔM 0.52), CSF/serum IgA quotient (Q IgA) (p < 0.001; ΔM 0.15) and CSF/serum IgM quotient (Q IgM) (p < 0.001; ΔM 0.09). Age showed a significant effect throughout most CSF markers, most strongly for CSF protein (p < 0.001; η2 = 0.16) and Q Alb (p < 0.001; η2 = 0.23). Both parameters increased significantly with age, leading to higher mean values in older individuals.

INTERPRETATION: For almost all markers in CSF, a significant effect of age alone on the markers or a significant effect of sex and age on the markers could be detected. Our study underscores the importance of age- and sex-adjusted reference values for the interpretation of CSF markers in clinical practice.