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Large-vessel hemodynamics are associated with glymphatic dysfunction and cognitive impairment in cerebral small

Dan Luo1, Peng Zeng1, Bang Zeng1

  • 1Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
|October 10, 2025
PubMed

Insights

Altered cerebral blood flow in cerebral small vessel disease (CSVD) is linked to impaired brain clearance and cognitive decline. Vascular health is crucial for maintaining brain function and cognitive aging.

Area of Science:

  • Neuroimaging
  • Cerebrovascular Health
  • Brain Aging

Background:

  • Cerebral hemodynamic disruption can impair brain clearance, contributing to age-related brain pathology.
  • Cerebral small vessel disease (CSVD) is a common age-related condition affecting brain hemodynamics and clearance pathways.

Purpose of the Study:

  • To investigate the interplay between large-vessel hemodynamics and glymphatic neuroimaging markers in CSVD.
  • To understand how vascular changes in CSVD impact brain clearance mechanisms.

Main Methods:

  • Utilized 4D flow MRI to quantify hemodynamic parameters (pulsatility index, wall shear stress) in carotid arteries and superior sagittal sinus.
  • Assessed glymphatic function using free water (FW) fraction and along the perivascular space (ALPS) measurements via diffusion-weighted imaging.
  • Employed multivariate regressions and mediation analyses to examine relationships between vascular and glymphatic markers, adjusting for covariates.

Main Results:

  • CSVD patients showed increased arterial/venous pulsatility and wall shear stress, correlating with elevated free water in basal ganglia and hippocampus.
  • Pulsatility in the internal carotid artery correlated with ALPS, while in healthy controls, inverse associations were observed between vascular and glymphatic markers.
  • Free water in the basal ganglia mediated the effect of carotid artery pulsatility on CSVD burden, and elevated superior sagittal sinus wall shear stress predicted poorer global cognition.

Conclusions:

  • Altered large-vessel hemodynamics are associated with glymphatic dysfunction and cognitive impairment in CSVD.
  • Vascular health plays a critical role in maintaining brain clearance mechanisms and cognitive function during aging.
Abstract

Keywords:
Diffusion magnetic resonance imagingFree waterGlymphatic systemPulsatile flowWall shear stress

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