Baseline peripheral inflammatory profiles predict phenoconversion in prodromal Parkinson's disease: a longitudinal...

Autonomic dysfunction is an early and prognostically important feature of Parkinson's disease, yet accessible biomarkers capturing systemic inflammatory processes potentially linked to autonomic dysfunction during the prodromal phase remain limited. We evaluated whether complete blood count-derived inflammatory indices predict phenoconversion in prodromal Parkinson's disease.

We conducted a retrospective cohort analysis of 452 prodromal participants from the Parkinson's Progression Markers Initiative. Five complete blood count-derived inflammatory indices-the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, systemic immune-inflammation index, and systemic inflammation response index-were evaluated using Cox proportional hazards models with penalized variable selection, sex-stratified analyses, and internal validation.

During follow-up, 43 participants (9.5%) phenoconverted. The systemic inflammation response index showed the strongest and most consistent association with phenoconversion, remaining independently associated after penalized variable selection (hazard ratio 2.34 per log-unit, 95% confidence interval 1.28-4.29; optimism-corrected concordance statistic 0.683; calibration slope 0.864). Effect estimates were larger in male participants, while female estimates were imprecise as a result of limited events; no statistically significant biomarker-by-sex interaction was detected. Longitudinal analyses indicated that baseline inflammatory levels, rather than subsequent changes, carried the primary prognostic signal.

Baseline systemic inflammation response index derived from routine complete blood counts was associated with phenoconversion risk in prodromal Parkinson's disease, although with a relatively low number of phenoconversion events. External validation of these findings with larger, independent cohorts would further support its utility in peripheral systemic inflammatory conditions such as those observed in autonomic dysfunctions.