Association between plasma neurofilament light chain levels and cognition in early Parkinson's disease

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Abstract Background Plasma neurofilament light chain (NfL) levels reflect large calibre myelinated axonal loss; and has been proposed as a blood‐based biomarker for neurodegeneration in dementia and parkinsonian disorders. Recent studies have suggested an association between increased plasma NfL levels and worse global cognition in Parkinson’s Disease (PD) patients. However, its relationship with specific cognitive domains remain unclear. This study thus aims to investigate the association between plasma NfL and cognitive domains in early PD. Method Plasma NfL was measured using Quanterix’s Single Molecule Array (Simoa) technology in a total of 197 subjects (175 early PD patients and 22 healthy controls). Cognitive function was assessed using a standard battery of neuropsychological tests. This included the Mini‐Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) as tests of global cognition, as well as two tests for each of five relevant cognitive domains, namely episodic memory, language, working memory, visuospatial, and executive function. Result PD patients had higher plasma NfL levels (mean=16.3 pg/ml, SD=8.59) compared to healthy controls (mean=12.2 pg/ml, SD=4.18) (p=.023). Amongst PD patients, increased NfL levels associated significantly with worse global cognition scores (MMSE: b=‐1.11 p=.009; MoCA: b=‐1.27, p=.026). In particular, higher levels of plasma NfL significantly correlated with poorer episodic memory (b=‐.541, p=.003) and executive function scores (b=‐.427, p=.002). No significant associations were found between plasma NfL and cognitive measures in healthy controls. Conclusion Higher plasma NfL levels were found in PD patients compared to healthy controls and associated significantly with poorer global cognitive function in PD. Interestingly, higher NfL levels correlated with worse episodic memory and executive function. These results implicate plasma NfL’s role as a potential biomarker for cognition in PD. Further studies are required to validate these findings.

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