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This is a Quantitative Study study.

September 17, 2025

White matter hyperintensity iron overload mediates glymphatic system dysfunction and cognitive impairment in cerebral small vessel disease

Key Points

WMH iron burden mediated the relationship between glymphatic system function and cognitive scores in CSVD, highlighting a pathway for cognitive decline.
A significant correlation was observed, where increased WMH iron levels were associated with lower cognitive function as measured by cognitive scores.
Utilizing DTI analysis to determine the glymphatic system's function, this study employed mediation analyses to elucidate the connection between iron burden and cognitive impairment.
These findings may inform future therapeutic strategies targeting iron overload to potentially mitigate cognitive impairment linked to CSVD.

Abstract

Motivation: The mechanism underlying the relationship between glymphatic system dysfunction and cognitive impairment in cerebral small vessel disease (CSVD) remains unclarified. Goal(s): This study aimed to explore the role white matter hyperintensity (WMH) iron burden played in the pathogenesis of CSVD. Approach: WMH iron burden was calculated using iterAtive magnetic suscePtibility sources sepARaTion QSM (APART-QSM), a sub-voxel quantitative method. Glymphatic system function was measured by DTI analysis ALong the Perivascular Space (DTI-ALPS) index. The relationships between WMH iron burden, DTI-ALPS index, and cognitive scores were examined through correlation and mediation analyses. Results: WMH iron burden mediated DTI-ALPS index and cognitive score in CSVD. Impact: Noninvasively, this study found WMH iron overload as a potential mediator in the relationship between glymphatic system dysfunction and cognitive impairment in CSVD, offering new insights for elucidating the pathological mechanisms underneath.

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