Prognostic significance of peripheral neutrophils and lymphocytes in early untreated Parkinson’s disease: an 8-year follow-up study

Background To explore whether peripheral blood neutrophils and lymphocytes are associated with longitudinal motor and cognitive decline in patients with early Parkinson’s disease (PD) and, to uncover the disease-specific mechanisms underlying these associations. Methods Data were obtained from the Parkinson’s Progression Markers Initiative cohort. We included 376 patients with recently diagnosed, drug-naïve PD and 178 matched healthy controls. The patients underwent annual assessments, including the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part 3 test to measure motor function and the Montreal Cognitive Assessment (MoCA) to measure cognitive function, for up to 8 years of follow-up. Dopamine transporter (DAT) imaging was performed at baseline and the 1-year, 2-year and 4-year follow-up visits. Results At baseline, patients with PD showed higher neutrophil and lower lymphocyte counts, resulting in a higher neutrophil-to-lymphocyte ratio (NLR) than that in healthy controls. Higher neutrophil counts were associated with a greater increase in MDS-UPDRS part 3 scores in patients with PD (estimate: 0.25, 95% CI: 0.12 to 0.37, p<0.001). Correspondingly, higher neutrophil levels were related to a greater reduction in DAT activity in the caudate (estimate: −0.007, 95% CI: −0.014 to −0.001, p=0.046) and putamen (estimate: −0.0039, 95% CI: −0.0077 to −0.0002, p=0.042). However, there were no significant effects of lymphocyte count and NLR on changes in the MDS-UPDRS part 3 and MoCA scores and striatal DAT uptake over time. Conclusion Among the blood biomarkers, only a higher neutrophil count was associated with faster motor progression along with accelerated nigrostriatal dopaminergic degeneration in patients with PD. The impact of neutrophils and lymphocytes on longitudinal cognitive changes remains unclear. Trial registration number NCT01141023 .