Regional differences in the link between water exchange rate across the blood–brain barrier and cognitive performance in normal aging

Valentinos Zachariou, Colleen Pappas, Christopher E. Bauer, Xingfeng Shao, Peiying Liu, Hanzhang Lu, Danny J.J. Wang, Brian T. Gold

Research output: Contribution to journalArticlepeer-review


The blood–brain barrier (BBB) undergoes functional changes with aging which may contribute to cognitive decline. A novel, diffusion prepared arterial spin labeling-based MRI technique can measure the rate of water exchange across the BBB (k w) and may thus be sensitive to age-related alterations in water exchange at the BBB. However, studies investigating relationships between k w and cognition have reported different directions of association. Here, we begin to investigate the direction of associations between k w and cognition in different brain regions, and their possible underpinnings, by evaluating links between k w, cognitive performance, and MRI markers of cerebrovascular dysfunction and/or damage. Forty-seven healthy older adults (age range 61–84) underwent neuroimaging to obtain whole-brain measures of k w, cerebrovascular reactivity (CVR), and white matter hyperintensity (WMH) volumes. Additionally, participants completed uniform data set (Version 3) neuropsychological tests of executive function (EF) and episodic memory (MEM). Voxel-wise linear regressions were conducted to test associations between k w and cognitive performance, CVR, and WMH volumes. We found that k w in the frontoparietal brain regions was positively associated with cognitive performance but not with CVR or WMH volumes. Conversely, k w in the basal ganglia was negatively associated with cognitive performance and CVR and positively associated with regional, periventricular WMH volume. These regionally dependent associations may relate to different physiological underpinnings in the relationships between k w and cognition in neocortical versus subcortical brain regions in older adults.

Original languageEnglish
Pages (from-to)265-282
Number of pages18
Issue number1
StatePublished - Feb 2024

Bibliographical note

Publisher Copyright:
© 2023, The Author(s).


  • BBB water exchange rate
  • Biological mechanisms
  • Cognitive performance
  • Normal aging

ASJC Scopus subject areas

  • Aging
  • Veterinary (miscellaneous)
  • Complementary and alternative medicine
  • Geriatrics and Gerontology
  • Cardiology and Cardiovascular Medicine


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