Sex-Related Differences in Regional Blood-Brain Barrier Integrity in Non-Demented Elderly Subjects

The role of the blood-brain barrier (BBB) breakdown has been recognized as being important in Alzheimer's disease pathogenesis. We aimed to evaluate whether regional BBB integrity differed according to sex and whether differences in BBB integrity changed as a consequence of aging or cognitive decline, using dynamic contrast-enhanced (DCE)-magnetic resonance imaging (MRI). In total, 75 participants with normal cognition (NC) or mild cognitive impairment (MCI) underwent cognitive assessments and MRI examination including DCE-MRI. Regional K-trans was calculated in cortical regions and the Patlak permeability model was used to calculate BBB permeability (K-trans, min(-1)). Females had a lower median K-trans in the cingulate and occipital cortices. In the "older old" group, sex differences in K-trans were only observed in the occipital cortex. In the MCI group, sex differences in K-trans were only observed in the occipital cortex. Age was the only predictor of cognitive assessment scores in the male MCI group; however, educational years and K-trans in the occipital cortex could predict cognitive scores in the female MCI group. Our study revealed that females may have better BBB integrity in cingulate and occipital cortices. We also found that sex-related differences in BBB integrity are attenuated with aging or cognitive decline.