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

White matter hyperintensities (WMH) are common MRI markers of cerebral small vessel disease, and systemic inflammation may contribute to their development.

The aim is to investigate the association between circulating inflammatory biomarkers and WMH burden.

PubMed, EMBASE, and the Cochrane Library (January 2010 to January 2025) were searched.

Studies reporting blood inflammatory biomarkers and quantitative WMH burden on brain MRI were included. Studies not published in English, nonhuman studies, retracted publications, reviews, and reports without extractable data were excluded. Of 392 records, 309 unique records were screened; 29 studies met inclusion criteria, and 11 were included in the meta-analysis (n=8846).

Study and patient characteristics, WMH volume, and sample size were extracted. Methodologic quality was assessed with Methodologic Index for Nonrandomized Studies and certainty of evidence with Grading of Recommendations, Assessment, Development, and Evaluations.

Random-effects meta-analysis and meta-regression were performed. Heterogeneity was substantial (I ² = 99.9%), and the pooled mean WMH volume was 2576.4 mm³ (95% CI, 2391.4-2761.4). In univariate metaregression, age (β = 356.1; 95% CI, 125.5-586.2; P = .002) and diabetes (β = 652.4; 95% CI, 370.5-934.3; P < .001) were associated with greater WMH burden; in multivariate analysis, only diabetes remained significant (β = 442.0; 95% CI, 98.7-785.3; P = .01). C-reactive protein (CRP) was not significantly associated with WMH volume.

The overall certainty of evidence was low and between-study heterogeneity was high.

Diabetes and aging may be associated with higher WMH burden, whereas CRP shows no significant association.