Biomarkers

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 (k_w), 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 (k_w), 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 (k_w) 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 k_w 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 (k_w) 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.