BACKGROUND: Neurofilament light chain protein (NfL) is a promising biomarker of 
neurodegeneration.
OBJECTIVES: To determine whether plasma and CSF NfL (1) associate with motor or 
cognitive status in Parkinson's disease (PD) and (2) predict future motor or 
cognitive decline in PD.
METHODS: Six hundred and fifteen participants with neurodegenerative diseases, 
including 152 PD and 200 healthy control participants, provided a plasma and/or 
cerebrospinal fluid (CSF) NfL sample. Diagnostic groups were compared using the 
Kruskal-Wallis rank test. Within PD, cross-sectional associations between NfL 
and Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) and Mattis 
Dementia Rating Scale (DRS-2) scores were assessed by linear regression; 
longitudinal analyses were performed using linear mixed-effects models and Cox 
regression.
RESULTS: Plasma and CSF NfL levels correlated substantially (Spearman r = 0.64, 
P < 0.001); NfL was highest in neurocognitive disorders. PD participants with 
high plasma NfL were more likely to develop incident cognitive impairment (HR 
5.34, P = 0.005).
CONCLUSIONS: Plasma NfL is a useful prognostic biomarker for PD, predicting 
clinical conversion to mild cognitive impairment or dementia. © 2021 
International Parkinson and Movement Disorder Society.