Mid-life adiposity factors relate to blood-brain barrier integrity in late life

J Intern Med. 2007 Dec;262(6):643-50. doi: 10.1111/j.1365-2796.2007.01869.x. Epub 2007 Nov 7.


Objective: We explored the relationship between adiposity factors measured during mid-life and blood-brain barrier (BBB) integrity measured via the cerebrospinal fluid/serum (CSF/S) albumin ratio in late life. Adiposity factors included body mass index and blood levels of sex hormone binding globulin (SHBG) and leptin. Design. Retrospective analyses over 24 years within a longitudinal study.

Setting: Population-based sample. Subjects. Eighty-one women.

Main outcome measures: CSF/S albumin ratio.

Results: The CSF/S albumin ratio measured at age 70-84 years was higher amongst women who were overweight or obese (6.50 +/- 2.79 vs. 5.23 +/- 1.61, age-adjusted P = 0.012), and was inversely correlated with SHBG (age-adjusted r = -0.321, P < 0.005) at age 46-60 years. In stepwise regression models, SHBG predicted the CSF/S albumin ratio (beta = -0.017, R2 = 0.107, P = 0.007). The best model (R2 = 0.187) predicting CSF/S albumin ratio included SHBG, age group (age 46 years versus >46), overweight or obesity, and an age group by SHBG interaction.

Conclusions: Lower levels of SHBG in mid-life were related to worse BBB integrity in women after 24 years in late life, even considering other adiposity factors. SHBG may be important for understanding sex hormone-mediated mechanisms in brain health or as an independent marker of adipose tissue, the largest endocrine organ.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Albumins / cerebrospinal fluid
  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid
  • Blood-Brain Barrier*
  • Female
  • Humans
  • Leptin / blood
  • Linear Models
  • Middle Aged
  • Obesity / blood*
  • Obesity / cerebrospinal fluid
  • Overweight / blood
  • Overweight / cerebrospinal fluid
  • Retrospective Studies
  • Serum Albumin / analysis
  • Sex Hormone-Binding Globulin / analysis


  • Albumins
  • Biomarkers
  • Leptin
  • Serum Albumin
  • Sex Hormone-Binding Globulin