Association of peripheral blood inflammatory markers with white matter hyperintensities in the elderly

Systemic inflammation is implicated in cerebral small vessel disease, but comparative longitudinal data on specific peripheral blood inflammatory markers for white matter hyperintensities (WMH) in the elderly are limited. This longitudinal cohort study consecutively enrolled hospitalized patients (aged ≥ 60) with baseline cranial MRI. WMH severity was graded using the Fazekas scale. Neutrophil count (NC), neutrophil-to-lymphocyte ratio (NLR), and white blood cell-to-lymphocyte ratio (WLR) were measured. Associations with WMH presence/severity and 3-year radiological progression (Fazekas score increase ≥ 1) were assessed using multivariable logistic regression. Predictive performance was evaluated using area under the curve (AUC) analysis. Among 428 participants, 325 (75.9%) had WMH. Adjusted for confounders, higher NC, NLR, and WLR were independently associated with WMH presence (all P < 0.05). NLR and WLR were associated with both moderate and severe WMH, while NC was associated only with severe WMH. Adding these markers to a basic clinical model yielded modest AUC improvements (0.753 to 0.757–0.762). Dose-response analysis showed the highest quartile (Q4) of each marker was associated with severe WMH after FDR correction (NC: OR = 2.033; NLR: OR = 1.503; WLR: OR = 1.581). In 338 patients with follow-up, baseline Q4 levels strongly predicted 3-year WMH progression (NC: OR = 4.035; NLR: OR = 5.184; WLR: OR = 4.076). Elevated NC, NLR, and WLR are independently associated with WMH presence, severity, and future progression in older adults. NLR and WLR may serve as potential indicators across severity stages, while NC is linked to advanced disease. WLR, a readily calculable index, shows predictive value comparable to NLR. These findings identify these readily available markers as candidate biomarkers; however, external validation in community-based cohorts with repeated inflammatory profiling is required before their integration into CSVD risk stratification frameworks can be recommended. Not applicable.