Neurofilament Light Chain as a Biomarker for Cognitive Decline in Parkinson Disease

Abstract

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

Age‐Adjusted Serum Neurofilament Predicts Cognitive Decline in Parkinson's Disease (MARK‐PD)

“…We read with great interest the study by Aamodt and colleagues reporting that plasma neurofilament light (NfL) chain levels are associated with UPDRS III (Unified Parkinson's Disease Rating Scale, Part III) score but not the Mattis Dementia Rating Scale (DRS-2), whereas plasma NfL predicted cognitive decline (DRS-2 change) but not motor worsening (UPDRS III ≥5 points). 1 Interestingly, these findings are in line with our results that serum NfL was associated with UPDRS III but not Montreal Cognitive Assessment (MoCA) score, whereas serum NfL predicted cognitive decline (decrease in MoCA score >2 points) but not motor worsening (increase in UPDRS III >4 points) in the Biomarkers in Parkinson's Disease (MARK-PD) study. 2 Numerous studies have shown that blood NfL predicts cognitive decline in patients with Parkinson's disease, but cutoff values determined by receiver operating characteristic (ROC) analysis revealed very different results.…”

“…2 Numerous studies have shown that blood NfL predicts cognitive decline in patients with Parkinson's disease, but cutoff values determined by receiver operating characteristic (ROC) analysis revealed very different results. [1][2][3] Given that serum NfL levels increase by 3.35% per year in PD…”

Advances in Proteomic and Metabolomic Profiling of Neurodegenerative Diseases

“…Clinical features of this prodromal phase have been described, such as hyposmia, REM sleep behavior disorders (RBD), constipation, and depression, but they are unspecific. In this scenario, dopaminergic PET/SPECT imaging can detect preclinical dopamine dysfunction several years before disease manifestation in individuals at high risk, including those with RBD or a pathogenic dominantly inherited mutation (65)(66)(67).…”

“…A recent study (67) suggested that both plasma and CSF levels of NfL could be a useful prognostic biomarker for PD (67). The study included 152 PD patients, and showed that NfL levels in plasma and CSF predicted change in cross-sectional associations between NfL and the Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) and Mattis Dementia Rating Scale (DRS-2) scores using linear mixed-effects models.…”

Plasma MIA, CRP, and albumin predict cognitive decline in Parkinson’s Disease

“…10 In the plasma, both higher NfL and lower epidermal growth factor levels predict cognitive decline in PD. 11,12,13,14,15 Extracellular-vesicle-associated tau and amyloid β 42 have also been reported to correlate with cognition in PD. 16 Additionally, genetic variants have been linked to cognitive trajectory in PD, 17,18,19 with the most well-replicated effects on cognition seen for the APOE E4 allele 20,21,22,23 and PD-associated GBA variants.…”