Serum SHBG Levels are not Associated with Longitudinal Cognitive Decline in Mild Cognitive Impairment

Prior studies have noted gender differences in cognition, imaging, and pathological markers in mild cognitive impairment (MCI) subjects. Sex hormone-binding globulin (SHBG), a major controlling factor in the proportion of bioavailable versus bound testosterone and estrogen, has been proposed to contribute to links between hormones and dementia, but has not yet been investigated fully in a prospective biomarker trial.

This study examined whether, among subjects with MCI, SHBG levels predict future rate of cognitive decline.

We examine the effect of gender on cognitive decline and factors modulating potential gender differences in 378 MCI subjects (134 females, 244 males) in the Alzheimer's Disease Neuroimaging Initiative-1 (ADNI-1), followed for up to 8 years (mean ± SE, 4.0 ± 0.1 years). Cognition was assessed using the ADAS-cog-11. Multivariate models examined the effect of gender covarying for age, ApoE4, baseline cognition, years of education, and SHBG levels.

MCI women declined significantly faster than men in cognition over the follow up period. Baseline SHBG levels differed significantly between men and women (p < 0.0001), and by age in men, but not by ApoE4 status. In the multivariate models, SHBG levels were not a significant predictor of cognitive decline in men or women but ApoE4 status, baseline cognition, years of education, and female gender were.

SHBG levels did not influence the rate of cognitive decline in MCI. Further studies to confirm these findings and uncover other potential mechanisms of gender differences in the risk for AD may be warranted.