Objective: To assess the cerebral small vessel disease (CSVD) burden in progressive supranuclear palsy (PSP) and examine the relationships among peripheral inflammatory markers, CSVD imaging features, and clinical dysfunction.

Background: CSVD is an important contributor to cognitive impairment in neurodegenerative disorders, yet its prevalence and clinical relevance in PSP remain insufficiently characterized.

Method: Clinical symptoms were assessed using validated scales. CSVD burden was evaluated according to the 2023 STRIVE-2 criteria, including lacunar infarcts (LI), white matter hyperintensities (WMH), enlarged perivascular spaces (EPVS), and cerebral microbleeds. Peripheral inflammatory indices, including the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and systemic immune-inflammation index (SII), were calculated. Associations among inflammatory markers, neuroimaging variables, and clinical outcomes were analyzed.

Results: 68 PSP patients were included. LI were present in 60.3% of patients, and substantial burdens of WMH, EPVS, and microbleeds were observed. Heavy CSVD burden (score ≥3) was more frequent in PSP-RS and PSP-PGF. Patients with higher CSVD burden exhibited multidomain cognitive impairment involving attention, orientation, visuospatial ability, and language. Among CSVD markers, WMH showed the strongest association with cognitive performance. Peripheral inflammatory markers were positively correlated with periventricular WMH (PWMHs) and were associated with worse cognitive scores. After adjustment for potential confounders, ordinal logistic regression identified NLR (OR = 3.31, P = 0.002), MLR, and SII (OR = 1.004, P = 0.002) as independent predictors of PWMH, whereas their associations with deep WMH (DWMHs) were not significant. Multiple linear regression further indicated that systemic inflammatory burden, particularly SII (β = −0.048, P = 0.003), independently predicted cognitive impairment. Mediation analysis demonstrated that PWMHs significantly mediated the association between inflammatory markers and cognitive decline, whereas DWMHs showed no significant mediating effect.

Conclusion: CSVD is common in PSP and is associated with cognitive impairment. Peripheral systemic inflammation is independently associated with increased PWMH, which partially mediates cognitive decline, suggesting selective vulnerability of periventricular white matter to inflammatory injury.

Heatmap of Partial Spearman Correlations

Ordinal Logistic Regression Analysis

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MDS Abstracts - https://www.mdsabstracts.org/abstract/systemic-inflammation-and-cerebral-small-vessel-disease-in-progressive-supranuclear-palsy/