Imagine having a crystal ball that could foretell your future cognitive abilities. Well, scientists have discovered something just as magical: neurofilament light chain protein (NfL) in cerebrospinal fluid (CSF). This protein can reflect the severity of neurodegeneration in individuals with Parkinson’s disease (PD). In a recent study, researchers examined the dynamic profiles of CSF NfL in de novo PD patients and found that it has the potential to predict cognitive progression and decline. They recruited 259 participants, including healthy controls and PD patients, and analyzed their CSF samples over a period of several years. The results showed that baseline levels and longitudinal changes in CSF NfL were associated with cognitive decline in PD patients, especially those who were older, male, less educated, or did not carry a specific genetic variant. Interestingly, CSF NfL levels also predicted the risk of PD with dementia in the future. These findings suggest that CSF NfL could be a promising biomarker for monitoring cognitive decline and predicting the prognosis of PD. To dive deeper into this groundbreaking research, check out the full article!

BackgroundNeurofilament light chain protein (NfL) in cerebrospinal fluid (CSF) reflects the severity of neurodegeneration, with its altered concentrations discovered in Parkinson’s disease (PD) and Parkinson’s disease dementia (PD-D).ObjectiveTo determine whether CSF NfL, a promising biomarker of neuronal/axonal damage, can be used to monitor cognitive progression in de novo Parkinson’s disease and predict future cognitive decline.MethodsA total of 259 people were recruited in this study, including 85 healthy controls (HC) and 174 neonatal PD patients from the Parkinson’s Progression Markers Initiative (PPMI). Multiple linear regression and linear mixed effects models were used to examine the associations of baseline/longitudinal CSF NfL with cognitive decline and other CSF biomarkers. Kaplan–Meier analysis and log-rank test were used to compare the cumulative probability risk of cognition progression during the follow-up. Multivariate cox regression was used to detect cognitive progression in de novo PD.ResultsWe found PD patients with mild cognitive impairment (PD-MCI) was higher than with normal cognition (PD-NC) in terms of CSF NfL baseline levels (p = 0.003) and longitudinal increase rate (p = 0.034). Both baseline CSF NfL and its rate of change predicted measurable cognitive decline in de novo PD (MoCA, β = −0.010, p = 0.011; β = −0.0002, p < 0.001, respectively). The predictive effects in de novo PD patients aged >65, male, ill-educated (<13 years) and without carrying Apolipoprotein E ε4 (APOE ε4) seemed to be more obvious and reflected in more domains investigated. We also observed that CSF NfL levels predicted progression in de novo PD patients with different cognitive diagnosis and amyloid status. After an average follow-up of 6.66 ± 2.54 years, higher concentration above the median of baseline CSF NfL was associated with a future high risk of PD with dementia (adjusted HR 2.82, 95% CI: 1.11–7.20, p = 0.030).ConclusionOur results indicated that CSF NfL is a promising prognostic predictor of PD, and its concentration and dynamics can monitor the severity and progression of cognitive decline in de novo PD patients.

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