Blood–brain barrier permeability in Alzheimer's disease: a case–control MRI study

Blood-brain barrier (BBB) dysfunction may contribute to the risk of Alzheimer's disease (AD). Dynamic contrast-enhanced magnetic resonance imaging (MRI) was performed repeatedly nine times before and up to 30 min following a 20 ml Gd-DTPA bolus injection in 15 AD participants and 15 healthy older people. For each participant, small circular regions of interest (size: 9 voxels) were placed to sample widely the deep gray matter (12 regions), cortical gray matter (72 regions), white matter (72 regions) and CSF (8 regions) as well as the basilar and internal carotid arteries (3 regions). Data were analysed using mixed effects models. There was no overall significant difference for AD subjects versus controls, but there was a significant effect for the time-by-AD interaction. Estimated marginal means remained essentially unchanged in AD subjects, but increased slowly after 15 min in healthy controls. An initial rise in gray matter MRI signal intensity followed by a later increase was also seen in AD participants after adjusting for CSF MRI signal intensities. The data suggest that BBB permeability is present even at an early stage of AD. Though the extent of leakage was no greater than that of non-demented people of a similar age in this small sample, the temporal pattern differed, indicating different blood–brain–CSF compartmental kinetics.