Serum Neurofilament Light Chain as a Marker of Progression in Parkinson's Disease: Long-Term Observation and Implications of Clinical Subtypes.

BACKGROUND

Biochemical and clinical biomarkers correlate with progression rate and disease severity in Parkinson's disease (PD) but are not sufficiently studied in late PD.

OBJECTIVE

To examine how serum neurofilament light chain (S-NfL) alone or combined with clinical classifications predicts PD outcome in later disease stages.

METHODS

Eighty-five patients with 7.9±5.1 years of PD duration were included in an observational cohort. Clinical scores were obtained at two separate examinations 8.2±2.0 years apart. S-NfL levels were determined with single molecule array (SiMoA). Five predefined disease progression milestones were assessed. After affirming combination potential of S-NfL and either of two clinical classifications, three combined models were constructed based on these factors and age at onset in different combinations.

RESULTS

S-NfL levels showed significant hazard ratios for four out of five disease progression milestones: walking-aid usage (HR 3.5; 95% CI 1.4-8.5), nursing home living (5.1; 2.1-12.5), motor end-stage (6.2; 2.1-17.8), and death (4.1; 1.7-9.7). Higher S-NfL levels were associated with lower ability in activities of daily living and poorer cognition at baseline and/or at follow-up. Combined models showed significantly improved area under receiver operating characteristic curves (0.77-0.91) compared to S-NfL levels alone (0.68-0.71) for predicting the five disease milestones.

CONCLUSION

S-NfL levels stratified patients according to their likelihood to reach clinically relevant progression milestones during this long-term observational study. S-NfL alone reflected motor and social outcomes in later stages of PD. Combining S-NfL with clinical factors was possible and exploratory combined models improved prognostic accuracy.