# Iron dysregulation in cerebral small vessel disease: A quantitative susceptibility mapping study revealing spatial patterns and cognitive predictive value

## TL;DR

This study uses MRI to show how iron levels in brain lesions linked to small vessel disease predict cognitive decline over time.

## Contribution

The study introduces spatial gradient analysis of iron metabolism in cerebral small vessel disease using quantitative susceptibility mapping.

## Key findings

- WMH susceptibility values predict future decline in information processing speed over 20.6 months.
- QSM provides independent cognitive risk information beyond traditional volumetric measures.
- Iron metabolism alterations bridge vascular and neurodegenerative pathways in dementia.

## Abstract

•First spatial gradient analysis of iron metabolism in CSVD using quantitative susceptibility mapping.•WMH susceptibility values predict future decline in information processing speed over 20.6 months.•Distinct pathophysiological patterns revealed between WMH cores and perilesional regions.•QSM provides independent cognitive risk information beyond traditional volumetric measures.•Iron metabolism alterations bridge vascular and neurodegenerative pathways in dementia.

First spatial gradient analysis of iron metabolism in CSVD using quantitative susceptibility mapping.

WMH susceptibility values predict future decline in information processing speed over 20.6 months.

Distinct pathophysiological patterns revealed between WMH cores and perilesional regions.

QSM provides independent cognitive risk information beyond traditional volumetric measures.

Iron metabolism alterations bridge vascular and neurodegenerative pathways in dementia.

White matter hyperintensities (WMHs) represent a cardinal feature of cerebral small vessel disease (CSVD), yet iron dysregulation alterations within these lesions and their relationship to cognitive decline remains poorly understood.

To characterize iron dysregulation in WMH using quantitative susceptibility mapping (QSM) and examine their relationship with CSVD severity and cognitive function.

Cross-sectional study with longitudinal follow-up component.

Single-center study at Shandong Provincial Hospital Affiliated with Shandong First Medical University, China.

299 participants recruited from January 2021 to September 2023, with 71 participants completing longitudinal follow-up (mean interval 20.6 months). Participants were categorized into early CSVD (0 points, n = 171), mild CSVD (1 point, n = 70), and severe CSVD (≥2 points, n = 58) groups based on total burden scoring.

None (observational study).

3.0T MRI with quantitative susceptibility mapping and diffusion tensor imaging. Spatial analysis examined susceptibility values in WMH cores and perilesional zones (0–2 mm, 2–4 mm, 4–6 mm). Cognitive assessments included Montreal Cognitive Assessment (MoCA), Symbol Digit Modalities Test (SDMT), and other neuropsychological tests.

WMH susceptibility values were significantly lower than normal-appearing white matter (-14.55 vs -7.77 ppb, P < 0.001) with progressive increases correlating with CSVD severity (P < 0.001). Cross-sectionally, higher WMH susceptibility values correlated with lower MoCA scores (r = -0.155, P = 0.045). Longitudinally, WMH susceptibility values predicted decline in information processing speed (SDMT: β = -0.247, P = 0.042). Spatial analysis revealed distinct patterns with perilesional regions showing intermediate susceptibility values.

Iron dysregulation alterations within WMH provide independent information about cognitive risk in CSVD. QSM emerges as a promising biomarker for monitoring cognitive trajectory and may facilitate early identification of patients at risk for cognitive decline.

Image, graphical abstract