Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Feb 5;17(1):14.
doi: 10.1186/s12987-020-0173-2.

Increased age and male sex are independently associated with higher frequency of blood-cerebrospinal fluid barrier dysfunction using the albumin quotient

Massimiliano Castellazzi  1   2 , Andrea Morotti  3 , Carmine Tamborino  4 , Francesca Alessi  5 , Silvy Pilotto  5 , Eleonora Baldi  2   6 , Luisa M Caniatti  2   6 , Alessandro Trentini  1 , Ilaria Casetta  1   2 , Enrico Granieri  1   2 , Maura Pugliatti  7   8 , Enrico Fainardi  2   9 , Tiziana Bellini  1   2   10
Affiliations

Increased age and male sex are independently associated with higher frequency of blood-cerebrospinal fluid barrier dysfunction using the albumin quotient

Massimiliano Castellazzi et al. Fluids Barriers CNS. .

Abstract

Background: The cerebrospinal fluid (CSF)/serum quotient of albumin (QAlb) is the most used biomarker for the evaluation of blood-cerebrospinal fluid barrier (B-CSF-B) permeability. For years QAlb was considered only as an age-related parameter but recently it has also been associated to sex. The aim of the present study was to explore the impact of sex in the determination of B-CSF-B dysfunction.

Methods: The analysis was retrospectively conducted on subjects consecutively admitted to the neurological ward. CSF and serum albumin levels were measured by immunonephelometry and pathological QAlb thresholds were considered: 6.5 under 40 years, 8.0 in the age 40-60 and 9.0 over 60 years.

Results: 1209 subjects were included in the study. 718 females and 491 males (age: 15-88 years): 24.6% of patients had a diagnosis of multiple sclerosis, 23.2% suffered from other inflammatory neurological diseases, 24.6% were affected by non-inflammatory neurological diseases, and for 27.6% of patients the final neurological diagnosis could not be traced. Dysfunctional B-CSF-B was detected more frequently (44 vs. 20.1%, p < 0.0001) and median QAlb value were higher (7.18 vs. 4.87, p < 0.0001) in males than in females in the overall study population and in all disease subgroups. QAlb and age were positively correlated both in female (p < 0.0001) and male (p < 0.0001) patients, however the slopes of the two regression lines were not significantly different (p = 0.7149), while the difference between the elevations was extremely significant (p < 0.0001) with a gap of 2.2 units between the two sexes. Finally, in a multivariable linear regression analysis increased age and male sex were independently associated with higher QAlb in the overall study population (both p < 0.001) and after stratification by age and disease group.

Conclusions: Accordingly, identification and validation of sex-targeted QAlb thresholds should be considered as a novel tool in an effort to achieve more precision in the medical approach.

Keywords: Age; Blood–cerebrospinal fluid barrier (B-CSF-B); Cerebrospinal fluid (CSF) analysis; Quotient of albumin (QAlb); Sex.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Linear regression analysis of albumin quotient (QAlb) and age in male and female patients. aQAlb and age were positively correlated in male (Spearman, p < 0.0001) and female (Spearman, p < 0.0001) patients. bThe slopes of the two regression lines were not significantly different (F test, p = 0.7149). cThe difference between the elevations was significant (F test, p < 0.0001)
Fig. 2
Fig. 2
Correlations between age and albumin levels in cerebrospinal fluid (CSF) and serum. Serum albumin levels decreased with age in all patients analysed as a whole (Spearman: p < 0.0001) and grouped by sex (Spearman: p < 0.0001 for woman and p < 0.0001 for men). CSF albumin levels increased with age in the entire population (Spearman: p < 0.0001) and in the female subgroup (Spearman: p < 0.0001). The CSF/serum albumin ratio (QAlb) increased with age in all patients analysed as a whole (Spearman: p < 0.0001) and grouped by sex (Spearman: p < 0.0001 in women and p = 0.0191 in men). CI confidence interval
See this image and copyright information in PMC

References

    1. Bechmann I, Galea I, Perry VH. What is the blood–brain barrier (not)? Trends Immunol. 2007;28:5–11. doi: 10.1016/j.it.2006.11.007. - DOI - PubMed
    1. Liddelow SA. Fluids and barriers of the CNS: a historical viewpoint. Fluids Barriers CNS. 2011;8:2. doi: 10.1186/2045-8118-8-2. - DOI - PMC - PubMed
    1. Engelhardt B, Ransohoff RM. Capture, crawl, cross: the T cell code to breach the blood–brain barriers. Trends Immunol. 2012;33:579–589. doi: 10.1016/j.it.2012.07.004. - DOI - PubMed
    1. Freedman MS, Thompson EJ, Deisenhammer F, et al. Recommended standard of cerebrospinal fluid analysis in the diagnosis of multiple sclerosis: a consensus statement. Arch Neurol. 2005;62:865–870. doi: 10.1001/archneur.62.6.865. - DOI - PubMed
    1. Deisenhammer F, Bartos A, Egg R, et al. Guidelines on routine cerebrospinal fluid analysis. Report from an EFNS task force. Eur J Neurol. 2006;13:913–922. doi: 10.1111/j.1468-1331.2006.01493.x. - DOI - PubMed