What is the clinical evidence from this study?

Study design: Cross-Sectional. Population: Aging and Blood-Brain-Barrier Dysfunction (n=30). Intervention: Quantitative Permeability Mapping (QPM) MRI. Primary outcome: Blood-brain barrier water exchange rate (kW) in cerebral cortex vs cerebral white matter (p=<0.0001).

April 8, 2022Frontiers in Aging Neuroscience56 citationsOpen Access

Quantitative Water Permeability Mapping of Blood-Brain-Barrier Dysfunction in Aging

Q: What are the key findings of this study?

Quantitative Permeability Mapping revealed that blood-brain barrier water exchange rate was significantly higher in the cerebral cortex (81.51 min-1) than white matter (75.19 min-1) and decreased with age.

JFJeremy N. FordHarvard University QZQihao ZhangJinan University ESElizabeth SweeneyGeorge Washington University

Key Result

Quantitative Permeability Mapping revealed that blood-brain barrier water exchange rate was significantly higher in the cerebral cortex (81.51 min-1) than white matter (75.19 min-1) and decreased with age.

Study Design

Type

Cross-Sectional (n=30)

Multicenter

Structured PICO

Population

30 adults without dementia across the age spectrum

Intervention

Diffusion-weighted arterial spin labeling (DW-ASL) MRI for Quantitative Permeability Mapping

Outcome

Blood-brain-barrier water exchange rate (kW) in whole brain and specific regionssurrogate

DW-ASL MRI can map blood-brain-barrier water exchange rates, revealing significant associations between aging and BBB dysfunction in specific brain regions.

Main Result

Absolute Event Rate: 81.51% vs 75.19%

p-value: p=<0.0001

Limitations

Sample size is relatively small and heterogeneous
May not be reflective of the general population in terms of racial and ethnic diversity
A small number in the 65+ group may have undiagnosed mild cognitive impairment
Amyloid status of subjects could not be ascertained
Brain-blood partition coefficient λ may not be uniform across brain regions
Cross-sectional design limits causal inferences

Abstract

Blood-brain-barrier (BBB) dysfunction is a hallmark of aging and aging-related disorders, including cerebral small vessel disease and Alzheimer’s disease. An emerging biomarker of BBB dysfunction is BBB water exchange rate (k W ) as measured by diffusion-weighted arterial spin labeling (DW-ASL) MRI. We developed an improved DW-ASL sequence for Quantitative Permeability Mapping and evaluated whole brain and region-specific k W in a cohort of 30 adults without dementia across the age spectrum. In this cross-sectional study, we found higher k W values in the cerebral cortex (mean = 81.51 min –1 , SD = 15.54) compared to cerebral white matter (mean = 75.19 min –1 , SD = 13.85) ( p 0.0001). We found a similar relationship for cerebral blood flow (CBF), concordant with previously published studies. Multiple linear regression analysis with k W as an outcome showed that age was statistically significant in the cerebral cortex ( p = 0.013), cerebral white matter ( p = 0.033), hippocampi ( p = 0.043), orbitofrontal cortices ( p = 0.042), and precunei cortices ( p = 0.009), after adjusting for sex and number of vascular risk factors. With CBF as an outcome, age was statistically significant only in the cerebral cortex ( p = 0.026) and precunei cortices ( p = 0.020). We further found moderate negative correlations between white matter hyperintensity (WMH) k W and WMH volume ( r = −0.51, p = 0.02), and normal-appearing white matter (NAWM) and WMH volume ( r = −0.44, p = 0.05). This work illuminates the relationship between BBB water exchange and aging and may serve as the basis for BBB-targeted therapies for aging-related brain disorders.

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