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Peer-reviewedCC BY 4.0Frontiers in Neurology

Associations of serum Hcy, SAP, NfL, and carotid plaque Crouse score with white-matter hyperintensities in older patients with cerebral small-vessel disease

  • Bo Ren1
  • Yuanyuan Ma1
  • Wenjing Mao1
  • Xiaokun Wu1
  1. 1Fourth Department of Neurology, North China University of Science and Technology Affiliated Hospital
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Abstract

Background and purpose: This study aimed to investigate the correlations of serum homocysteine (Hcy), serum amyloid P component (SAP), neurofilament light chain (NfL), and carotid plaque Crouse score with white matter hyperintensities (WMH) in elderly patients with cerebral small-vessel disease (CSVD).

Methods: A total of 382 MRI-confirmed elderly CSVD patients hospitalized in the Department of Neurology, North China University of Science and Technology Affiliated Hospital from July 2022 to June 2024 were enrolled. Patients were divided into WMH-positive and WMH-negative groups, and WMH-positive cases were further stratified into mild, moderate, and severe subgroups via the Fazekas scale. We compared serum Hcy, SAP, NfL levels and carotid plaque Crouse score among groups. Spearman rank-order correlation was used to analyze the relationships between the above indicators and WMH severity. Binary logistic regression identified independent correlates for WMH occurrence, while ordinal logistic regression together with the proportional-odds (parallel-lines) test to explore independent correlates of WMH severity. ROC curve analysis evaluated the diagnostic performance of each indicator. A two-sided p < 0.05 was defined as statistically significant.

Results: Age, serum Hcy, SAP, NfL levels and carotid plaque Crouse score were significantly higher in the WMH-positive group (all p < 0.05). All indicators increased stepwise with the aggravation of WMH lesions, and pairwise comparisons showed significant differences among mild, moderate and severe subgroups (all p < 0.05). Spearman analysis confirmed that all indicators were positively correlated with WMH severity (all p < 0.001). After adjusting for confounding factors, age, serum Hcy, SAP, NfL and carotid plaque Crouse score were independently associated with WMH occurrence and severity (all p < 0.05). All indicators showed certain diagnostic value for CSVD-related WMH; SAP had the optimal efficacy, Crouse score and Hcy presented high specificity, while NfL showed the weakest discriminatory ability.

Conclusion: Serum Hcy, SAP, NfL and carotid plaque Crouse score were independently associated with WMH occurrence and severity in elderly CSVD patients. These indicators exhibit diagnostic performance for CSVD-related WMH, with SAP showing the best diagnostic value. They can provide reliable references for early clinical screening and severity evaluation of WMH. Further studies are required to clarify the underlying pathophysiological mechanisms of these associations.

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Cite

BibTeXRIS
BibTeX
@article{ren2026associations,
  title = {{Associations of serum Hcy, SAP, NfL, and carotid plaque Crouse score with white-matter hyperintensities in older patients with cerebral small-vessel disease}},
  author = {Bo Ren and Yuanyuan Ma and Wenjing Mao and Xiaokun Wu},
  journal = {Frontiers in Neurology},
  year = {2026},
  month = oct,
  doi = {10.3389/fneur.2026.1977360},
  url = {https://www.frontiersin.org/articles/10.3389/fneur.2026.1977360/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Associations of serum Hcy, SAP, NfL, and carotid plaque Crouse score with white-matter hyperintensities in older patients with cerebral small-vessel disease
AU  - Bo Ren
AU  - Yuanyuan Ma
AU  - Wenjing Mao
AU  - Xiaokun Wu
PY  - 2026
DA  - 2026/10/21
JO  - Frontiers in Neurology
DO  - 10.3389/fneur.2026.1977360
UR  - https://www.frontiersin.org/articles/10.3389/fneur.2026.1977360/full
AB  - Background and purpose: This study aimed to investigate the correlations of serum homocysteine (Hcy), serum amyloid P component (SAP), neurofilament light chain (NfL), and carotid plaque Crouse score with white matter hyperintensities (WMH) in elderly patients with cerebral small-vessel disease (CSVD).  Methods: A total of 382 MRI-confirmed elderly CSVD patients hospitalized in the Department of Neurology, North China University of Science and Technology Affiliated Hospital from July 2022 to June 2024 were enrolled. Patients were divided into WMH-positive and WMH-negative groups, and WMH-positive cases were further stratified into mild, moderate, and severe subgroups via the Fazekas scale. We compared serum Hcy, SAP, NfL levels and carotid plaque Crouse score among groups. Spearman rank-order correlation was used to analyze the relationships between the above indicators and WMH severity. Binary logistic regression identified independent correlates for WMH occurrence, while ordinal logistic regression together with the proportional-odds (parallel-lines) test to explore independent correlates of WMH severity. ROC curve analysis evaluated the diagnostic performance of each indicator. A two-sided p < 0.05 was defined as statistically significant.  Results: Age, serum Hcy, SAP, NfL levels and carotid plaque Crouse score were significantly higher in the WMH-positive group (all p < 0.05). All indicators increased stepwise with the aggravation of WMH lesions, and pairwise comparisons showed significant differences among mild, moderate and severe subgroups (all p < 0.05). Spearman analysis confirmed that all indicators were positively correlated with WMH severity (all p < 0.001). After adjusting for confounding factors, age, serum Hcy, SAP, NfL and carotid plaque Crouse score were independently associated with WMH occurrence and severity (all p < 0.05). All indicators showed certain diagnostic value for CSVD-related WMH; SAP had the optimal efficacy, Crouse score and Hcy presented high specificity, while NfL showed the weakest discriminatory ability.  Conclusion: Serum Hcy, SAP, NfL and carotid plaque Crouse score were independently associated with WMH occurrence and severity in elderly CSVD patients. These indicators exhibit diagnostic performance for CSVD-related WMH, with SAP showing the best diagnostic value. They can provide reliable references for early clinical screening and severity evaluation of WMH. Further studies are required to clarify the underlying pathophysiological mechanisms of these associations.
SN  - 1664-2295
ER  -