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

Objective. Vascular dementia (VaD) is a progressive neurodegenerative disease with cognitive decline caused by cerebrovascular factors. Despite the great progress made in the past decade, VaD still lacks effective treatments and peripheral blood biomarkers. In this study, we tested the level of peripheral blood neurofilament light chain (NfL) in VaD patients and explored its relationship with cognitive impairment. Method. A total of 176 study subjects including 80 normal controls (NC) and 96 VaD patients were included in our study. Upon admission, we collected clinical and biochemical characteristics of all research subjects. We also evaluate the Montreal cognitive assessment scale (MoCA) scores of all subjects. The serum NfL level was measured by the single-molecule array (Simoa) method. Results. The years of education in the NC group and VaD group were ( 11.65 ± 3.04 ) years and ( 10.53 ± 3.87 ) years, respectively. Compared with VaD patients, the NC group has a higher level of education ( p = 0.037 ). Furthermore, the results of Simoa indicated that VaD subjects had higher serum NfL levels compared with the NC group [( 8.49 ± 2.37 ) pg/ml vs. ( 19.26 ± 4.71 ) pg/ml, p < 0.001 ]. In terms of other clinical and biochemical characteristics, there was no significant difference between VaD and NC. The Spearman correlation analysis indicated that educational years have a significant positive correlation with MoCA scores ( r = 0.238 , p = 0.041 ), while age and serum NfL levels have a significantly negative correlation with MoCA scores (age: r = − 0.213 , p = 0.040 ; NfL: r = − 0.395 , p = 0.027 ). However, further multiple regression analysis showed that only serum NfL level might serve as an independent risk factor for cognitive decline in VaD ( β = 0.317 , p = 0.021 ). Conclusion. The serum NfL levels in VaD subjects are significantly elevated, which may be used as a potential peripheral blood marker for predicting cognitive impairment in patients with VaD.

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Plasma glial fibrillary acidic protein and neurofilament light chain for the diagnostic and prognostic evaluation of frontotemporal dementia

Translational Neurodegeneration ◽

10.1186/s40035-021-00275-w ◽

2021 ◽

Vol 10 (1) ◽

Author(s):

Nuole Zhu ◽

Miguel Santos-Santos ◽

Ignacio Illán-Gala ◽

Victor Montal ◽

Teresa Estellés ◽

...

Keyword(s):

Glial Fibrillary Acidic Protein ◽

Cognitive Decline ◽

Frontotemporal Dementia ◽

Cortical Thickness ◽

Light Chain ◽

Diagnostic Performance ◽

Acidic Protein ◽

Neurofilament Light Chain ◽

Neurofilament Light

Abstract Background Astrocytes play an essential role in neuroinflammation and are involved in the pathogenesis of neurodenegerative diseases. Studies of glial fibrillary acidic protein (GFAP), an astrocytic damage marker, may help advance our understanding of different neurodegenerative diseases. In this study, we investigated the diagnostic performance of plasma GFAP (pGFAP), plasma neurofilament light chain (pNfL) and their combination for frontotemporal dementia (FTD) and Alzheimer’s disease (AD) and their clinical utility in predicting disease progression. Methods pGFAP and pNfL concentrations were measured in 72 FTD, 56 AD and 83 cognitively normal (CN) participants using the Single Molecule Array technology. Of the 211 participants, 199 underwent cerebrospinal (CSF) analysis and 122 had magnetic resonance imaging. We compared cross-sectional biomarker levels between groups, studied their diagnostic performance and assessed correlation between CSF biomarkers, cognitive performance and cortical thickness. The prognostic performance was investigated, analyzing cognitive decline through group comparisons by tertile. Results Unlike pNfL, which was increased similarly in both clinical groups, pGFAP was increased in FTD but lower than in AD (all P < 0.01). Combination of both plasma markers improved the diagnostic performance to discriminate FTD from AD (area under the curve [AUC]: combination 0.78; pGFAP 0.7; pNfL 0.61, all P < 0.05). In FTD, pGFAP correlated with cognition, CSF and plasma NfL, and cortical thickness (all P < 0.05). The higher tertile of pGFAP was associated with greater change in MMSE score and poor cognitive outcome during follow-up both in FTD (1.40 points annually, hazard ratio [HR] 3.82, P < 0.005) and in AD (1.20 points annually, HR 2.26, P < 0.005). Conclusions pGFAP and pNfL levels differ in FTD and AD, and their combination is useful for distinguishing between the two diseases. pGFAP could also be used to track disease severity and predict greater cognitive decline during follow-up in patients with FTD.

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Levels of plasma neurofilament light chain and cognitive function in patients with Alzheimer or Parkinson disease

Scientific Reports ◽

10.1038/s41598-018-35766-w ◽

2018 ◽

Vol 8 (1) ◽

Cited By ~ 51

Author(s):

Yung-Shuan Lin ◽

Wei-Ju Lee ◽

Shuu-Jiun Wang ◽

Jong-Ling Fuh

Keyword(s):

Cognitive Function ◽

Parkinson Disease ◽

Light Chain ◽

Neurofilament Light Chain ◽

Neurofilament Light

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Serum neurofilament light chain as a surrogate of cognitive decline in sporadic and familial Frontotemporal dementia

European Journal of Neurology ◽

10.1111/ene.15058 ◽

2021 ◽

Author(s):

Anuschka Silva‐Spínola ◽

Marisa Lima ◽

Maria João Leitão ◽

João Durães ◽

Miguel Tábuas‐Pereira ◽

...

Keyword(s):

Cognitive Decline ◽

Frontotemporal Dementia ◽

Light Chain ◽

Neurofilament Light Chain ◽

Neurofilament Light

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Plasma neurofilament light chain is associated with cognitive decline in non-dementia older adults

Scientific Reports ◽

10.1038/s41598-021-91038-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Lingxiao He ◽

John E. Morley ◽

Geetika Aggarwal ◽

Andrew D. Nguyen ◽

Bruno Vellas ◽

...

Keyword(s):

Older Adults ◽

Cognitive Decline ◽

Light Chain ◽

Cognitive Functions ◽

Linear Models ◽

Cognitive Status ◽

Neurofilament Light Chain ◽

Cross Sectional ◽

Neurofilament Light ◽

State Examination

AbstractNeurofilament light chain (NfL) has been associated with cognitive status in multiple neurodegenerative conditions. Studies about plasma NfL and cognitive decline in older adults are still limited. 504 older adults (median age 75 years) who expressed memory complaints were selected from the Multidomain Alzheimer’s Preventive Trial (MAPT) and were classified as normal cognition (NC) or mild cognitive impairment (MCI). Cognitive functions were measured as mini mental state examination (MMSE) and composite cognitive score (CCS) over a 4-year period. Plasma NfL was measured at the first or the second year of the MAPT. Mixed-effects linear models were performed to evaluate cross-sectional and longitudinal associations. In the whole population, higher plasma NfL was cross-sectionally associated with lower cognitive functions (MMSE: β = − 0.007, 95% CI [− 0.013, − 0.001]; CCS: β = − 0.003, 95% CI [− 0.006, − 0.001]). In adults with MCI, but not NC, higher plasma NfL was associated with lower CCS at the cross-sectional level (β = − 0.003, 95% CI [− 0.005, − 0.0002]). The upper quartile NfL group further demonstrated more over time decline in CCS (β = − 0.07, 95% CI [− 0.12, − 0.01]) under the MCI status. Plasma NfL can be a promising biomarker of progressive cognition decline in older adults with MCI.

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CSF and Circulating NFL as Biomarkers for the Discrimination of Parkinson Disease From Atypical Parkinsonian Syndromes: Meta-analysis

Neurology Clinical Practice ◽

10.1212/cpj.0000000000001116 ◽

2021 ◽

pp. 10.1212/CPJ.0000000000001116

Author(s):

Efthalia Angelopoulou ◽

Anastasia Bougea ◽

Andreas Papadopoulos ◽

Nikolaos Papagiannakis ◽

Athina-Maria Simitsi ◽

...

Keyword(s):

Diagnostic Accuracy ◽

Parkinson Disease ◽

Light Chain ◽

Meta Analysis ◽

Axonal Damage ◽

Neurofilament Light Chain ◽

Neurofilament Light ◽

Parkinsonian Syndromes ◽

High Diagnostic Accuracy ◽

Standard Deviations

Abstract:Purposeof review: To evaluate whether CSF and circulating neurofilament light chain (NFL), a marker of axonal damage, could discriminate Parkinson’s disease (PD) from atypical parkinsonian syndromes (APS).Recent findings:MEDLINE and SCOPUS were systematically searched, and fifteen studies were included (1035 PD patients,930 APS patients). CSF and circulating NFL levels were 1.26 and 1.53 standard deviations higher in APS compared to PD patients respectively [g=1.26 (95% CI 0.99-1.53);12 studies, 880 PD patients, 847 APS patients, g=1.53 (1.15-1.91);4 studies, 307 PD patients, 197 APS patients. Pooled areas under the curve were 0.941 (0.916-0.965) and 0.874 (0.802-0.946) for CSF and circulating NFL, corresponding to average sensitivities of 86% (79-90%) and 91% (86-95%), and specificity of 88% (82-92%) and 76% (62-85%), respectively.Summary:These results strongly support the high diagnostic accuracy of both CSF and circulating NFL in differentiating PD from APS, highlighting their usefulness as promising biomarkers.

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Neurofilament light chain related to longitudinal decline in frontotemporal lobar degeneration

Neurology Clinical Practice ◽

10.1212/cpj.0000000000000959 ◽

2020 ◽

pp. 10.1212/CPJ.0000000000000959

Author(s):

Jiasi Vicky Zhang ◽

David J. Irwin ◽

Kaj Blennow ◽

Henrik Zetterberg ◽

Edward B. Lee ◽

...

Keyword(s):

Cognitive Decline ◽

Light Chain ◽

Frontotemporal Lobar Degeneration ◽

Neurofilament Light Chain ◽

Neurofilament Light ◽

Cognitive Domains ◽

Diagnosis And Prognosis ◽

Language Measures ◽

Disease Modifying Treatment

ABSTRACTBackground:Accurate diagnosis and prognosis of frontotemporal lobar degeneration (FTLD) during life is an urgent concern in the context of emerging disease-modifying treatment trials. Few cerebrospinal fluid (CSF) markers have been validated longitudinally in patients with known pathology, and we hypothesized that CSF neurofilament light chain (NfL) would be associated with longitudinal cognitive decline in patients with known FTLD-TDP pathology.Methods:This case-control study evaluated CSF NfL, total-tau (tTau), phosphorylated-tau (pTau) and beta-amyloid (Aβ42) in known FTLD-Tau or FTLD-TDP pathology (n=50) and healthy controls (n=65), and an extended cohort of clinically-diagnosed patients with likely FTLD-Tau or FTLD-TDP (n=148). Regression analyses related CSF analytes to longitudinal cognitive decline (follow up ∼1 year), controlling for demographic variables and core AD CSF analytes.Results:In FTLD-TDP with known pathology, CSF NfL is significantly elevated compared to controls, and significantly associated with longitudinal decline on specific executive and language measures, after controlling for age, disease duration, and core AD CSF analytes. Similar findings are found in the extended cohort also including clinically-identified likely FTLD-TDP. While CSF NfL is elevated in FTLD-Tau compared to controls, the association between NfL and longitudinal cognitive decline is limited to executive measures.Conclusion:CSF NfL is associated with longitudinal clinical decline in relevant cognitive domains in patients with FTLD-TDP after controlling for demographic factors and core AD CSF analytes, and may also be related to longitudinal decline in executive functioning in FTLD-Tau.

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