Serum Neurofilament Predicts Mortality and Indicates Accelerated Neurodegeneration in Late-Stage Parkinson’s Disease

Abstract

Abstract Background A high percentage of dopaminergic axons are already lost at the time of diagnosis, current studies on neuroprotective agents focus mainly on the early stages of Parkinson’s disease (PD). Nevertheless, PD progresses slowly during the first years, making clinical trials challenging. The final phase of the disease, however, is characterized by a rapid deterioration with clinical milestones marking the transition. Objective To investigate whether PD is associated with increased neurodegeneration in the late stage rather than a functional or age-dependent deterioration. Methods Neurodegeneration was quantified in n = 118 patients with PD using serum neurofilament light chain (sNfL) as a biomarker. Late-stage PD was defined by a minimum disease duration of five years. The presence of clinical milestones (hallucinations, dementia, recurrent falls, and admission to a nursing home) and mortality was determined based on chart review. Results sNfL was higher in patients with late-stage PD who presented at least one clinical milestone and increased with a higher number of milestones (Spearman’s ρ = 0.66, p < 0.001). Above a cut-off value of 26.9 pg/ml, death was 13.6 times more likely (95% CI: 3.53–52.3, p < 0.001), corresponding to a sensitivity of 85.0% and a specificity of 86.8% (AUC 0.91, 95% CI: 0.85–0.97). Similar values were obtained when using an age-adjusted cut-off percentile of 90% for sNfL. Conclusion Our findings suggest that the rate of ongoing neurodegeneration is higher in advanced PD than in earlier disease stages, turning patients with advanced PD into an interesting target group for neuroprotective strategies. In this context, measuring sNfL could help identify patients at risk for clinical deterioration and in addition serve as an objective outcome measure for clinical trials.