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Published on: November 8, 2017
Blood-brain barrier permeability in Alzheimer's disease: a case-control MRI study
John M Starr1, Andrew J Farrall, Paul Armitage
1Geriatric Medicine Unit, University of Edinburgh, Scotland, UK. jstarr@stafmail.ed.ac.uk
Abstract:
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.
Insights
Blood-brain barrier (BBB) dysfunction is present in early Alzheimer's disease (AD). While leakage extent was similar to controls, the BBB
Area of Science:
- Neuroimaging
- Neurology
- Biomedical Engineering
Background:
- Blood-brain barrier (BBB) dysfunction is implicated in Alzheimer's disease (AD) pathogenesis.
- Understanding BBB permeability is crucial for early AD detection and therapeutic strategies.
Purpose of the Study:
- To investigate dynamic contrast-enhanced magnetic resonance imaging (MRI) patterns of BBB permeability in AD patients compared to healthy controls.
- To analyze temporal differences in BBB leakage and blood-brain-cerebrospinal fluid (CSF) kinetics.
Main Methods:
- Dynamic contrast-enhanced MRI was performed on 15 AD patients and 15 healthy controls.
- Gd-DTPA contrast agent was administered, with repeated scans over 30 minutes.
- Regions of interest were placed in gray matter, white matter, CSF, and major arteries for signal intensity analysis using mixed-effects models.
Main Results:
- No overall significant difference in BBB leakage extent between AD patients and controls.
- A significant time-by-AD interaction was observed, with BBB permeability remaining stable in AD subjects but increasing over time in controls.
- AD participants showed an initial gray matter signal rise followed by a later increase, suggesting altered blood-brain-CSF compartmental kinetics.
Conclusions:
- BBB permeability is present even in early stages of Alzheimer's disease.
- The temporal pattern of BBB leakage differs between AD patients and healthy individuals, indicating altered compartmental kinetics.
- Dynamic contrast-enhanced MRI reveals distinct BBB functional characteristics in AD, potentially aiding early diagnosis.
