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.
- PARKINSON'S DISEASE
Data availability statement
Data are available in a public, open access repository. All data reported in this article are available in the PPMI repository (www.ppmi-info.org).
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Contributors RK and J-SJ contributed to study conception and design. RK and J-SJ contributed to data acquisition and analysis. All authors contributed to data interpretation. RK and J-SJ contributed to drafting of the manuscript. All authors critically revised the manuscript and approved the final version. J-SJ is responsible for the overall content as guarantor.
Funding This work was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT) (No. 2021M3E5D1A02015184). This work was supported by the NRF grant funded by the Korea government (MSIT) (No. 2020R1C1C1013382 and 2021R1C1C1011822).
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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