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Published on: January 28, 2014
Biomarkers
Colleen Pappas1, Christopher E Bauer1, Valentinos Zachariou1
1University of Kentucky, Lexington, KY, USA.
Insights
Increased blood brain barrier (BBB) water exchange rate (kw) is linked to worsening white matter hyperintensities (WMHs) over time in older adults. This suggests BBB dysfunction may contribute to cerebrovascular disease progression.
Area of Science:
- Neuroimaging
- Cerebrovascular Disease Research
- Cognitive Impairment Studies
Background:
- Cerebrovascular disease (CVD) impacts cognitive function, contributing to cognitive impairment and dementia (VCID).
- Blood brain barrier (BBB) integrity is increasingly recognized as a factor in CVD.
- Magnetic resonance imaging (MRI) markers like white matter hyperintensities (WMHs) and free water (FW) are established CVD indicators.
Purpose of the Study:
- To investigate the relationship between BBB water exchange rate (kw), a measure of BBB function, and changes in WMHs and FW over approximately 2.5 years.
- To explore how baseline BBB function relates to the progression of cerebrovascular damage markers.
Main Methods:
- 68 older adults underwent neuroimaging using diffusion prepared pseudo-continuous arterial spin labeling (DP-pCASL) to measure BBB water exchange rate (kw), cerebral blood flow (CBF), and arterial transit time (ATT).
- WMH volume and white matter FW were quantified using MRI (FLAIR and diffusion-weighted imaging) at baseline and follow-up.
- Mixed-effects models analyzed associations between baseline DP-pCASL measures and changes in WMHs or FW, controlling for age, gender, and intracranial volume.
Main Results:
- Higher baseline BBB water exchange rate (kw) predicted an increase in WMHs over time, though not related at baseline.
- Higher baseline cerebral blood flow (CBF) was associated with fewer WMHs at baseline but not with longitudinal changes.
- Arterial transit time (ATT) showed no significant association with WMHs.
- Higher kw was related to lower FW cross-sectionally, but this did not persist longitudinally.
- CBF and ATT were not associated with FW at baseline or over time.
Conclusions:
- Preliminary findings indicate BBB water exchange rate (kw) is associated with longitudinal changes in WMHs and baseline FW.
- Increased water exchange across the BBB may increase susceptibility to white matter damage.
- Further research is needed to fully elucidate the impact of BBB efficiency on cerebrovascular health.
Background:
Understanding biological mechanisms related to cerebrovascular disease (CVD) can provide insight into vascular contributions to cognitive impairment and dementia (VCID). There has been increased interest in exploring blood brain barrier (BBB) function as it relates to other well-established CVD markers, such as magnetic resonance imaging (MRI) based white matter hyperintensities (WMHs) and free water (FW). Here, we examine how an MRI-metric of BBB function [water exchange rate (kw)] relates to change in WMHs and FW after approximately 2.5 years of follow-up.
Method:
A total of 68 older adults recruited from the University of Kentucky had neuroimaging data. Water exchange rate (kw) across the BBB was measured by diffusion prepared pseudo-continuous arterial spin labeling (DP-pCASL) at baseline for the whole brain. Cerebral blood flow (CBF) and arterial transit time (ATT) were also measured from the DP-pCASL sequence. Whole brain WMH volume was quantified using T2-weighted fluid-attenuated inversion recovery (FLAIR) and whole brain white matter FW was quantified using diffusion weighted imaging at baseline and follow-up. Mixed-effects models controlling for age, gender, and intracranial volume were used to test associations between baseline DP-pCASL measures (i.e. kw, CBF, ATT) and change in WMHs or FW between two visits.
Result:
Whole brain kw was not related to WMH volume at baseline, however, higher kw was associated with an increase in WMHs over time. Conversely, higher whole brain CBF was associated with fewer WMHs at baseline, but not with change over time. ATT was not related to WMHs at baseline or over time. When considering the FW measure, higher whole brain kw was related to lower FW cross-sectionally but results did not persist longitudinally. Both whole brain CBF and ATT were not associated with FW at baseline or over time.
Conclusion:
Our preliminary results suggest that BBB kw is related to change in WMHs over time and FW at baseline. Greater water exchange across the BBB may contribute to a greater susceptibility to white matter damage. The FW results are consistent with our prior studies correlating kw and FW. More work is needed to determine the effects of BBB efficiency on downstream cerebrovascular health.
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