Associations Between Nonspecific Blood-Derived Inflammatory Indices and MRI-Derived Frontal Network Degeneration in Progressive Supranuclear Palsy

Background: Progressive supranuclear palsy (PSP) is a primary 4-repeat tauopathy in which neurodegeneration may be accompanied by neuroinflammatory and peripheral immune alterations. Whether peripheral inflammatory activity reflects structural degeneration within vulnerable brain networks remains unclear. Methods: This retrospective case–control study included 12 patients with PSP and 12 patients with Parkinson’s disease (PD). Automated volumetric analysis of 3-Tesla MRI was performed using volBrain 2.0. Blood-derived inflammatory indices included neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), systemic inflammation response index (SIRI), and red blood cell distribution with coefficient of variation (RDW-CV). Results: Patients with PSP showed significantly lower normalized superior frontal gyrus and pallidal volumes than patients with PD. Within the PSP group, higher values of selected blood-derived inflammatory indices were associated with lower frontal network volumes. After adjustment for age, MLR was inversely associated with the composite Frontal Network Score (partial r = −0.7333, p = 0.0067, FDR q = 0.020). The strongest regional association was observed between SIRI and medial frontal cortex volume (rho = −0.748, p = 0.0051); however, regional associations did not remain significant after FDR correction. Conclusions: Peripheral inflammatory markers were associated with MRI-derived measures of frontal network degeneration in PSP. The association between MLR and the composite Frontal Network Score supports a link between systemic immune alterations and network-level neurodegeneration in PSP.