Examining the Association between Systemic Inflammation and White Matter Hyperintensities: A Systematic Review with...

Area of Science:

• Neurology
• Radiology
• Inflammation Research

Background:

• White matter hyperintensities (WMH) are common magnetic resonance imaging (MRI) indicators of cerebral small vessel disease.
• Systemic inflammation is a potential contributing factor to the development of WMH.

Purpose of the Study:

• To investigate the association between blood inflammatory markers and the burden of WMH.
• To analyze the relationship between specific inflammatory biomarkers and quantitative WMH measures.

Main Methods:

• A systematic review and meta-analysis of studies published between January 2010 and January 2025, searching PubMed, Embase, and Cochrane Library.
• Included studies reported blood inflammatory biomarkers and quantitative WMH burden on brain MRI. Excluded were non-English, non-human, retracted, review articles, and studies lacking extractable data.
• Eleven studies (n=8846) were included in the meta-analysis, with data extraction on patient characteristics, WMH volume, and sample size. Methodological quality and certainty of evidence were assessed using MINORS and GRADE.

Main Results:

• The meta-analysis revealed substantial heterogeneity (I² = 99.9%) with a pooled mean WMH volume of 2576.4 mm³.
• Univariate meta-regression indicated that age (P = .002) and diabetes (P < .001) were associated with increased WMH burden.
• In multivariate analysis, only diabetes remained a significant predictor of WMH burden (P = .01), while C-reactive protein (CRP) showed no significant association with WMH volume.

Conclusions:

• The certainty of evidence was low, and significant heterogeneity existed between studies.
• Diabetes and aging appear to be associated with a higher WMH burden.
• C-reactive protein (CRP) did not demonstrate a significant association with WMH burden in this meta-analysis.