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Serum Neurofilament Light Chain as a Marker of Progression in Parkinson's Disease : Long-Term Observation and Implications of Clinical Subtypes

Ygland Rödström, Emil LU ; Mattsson-Carlgren, Niklas LU orcid ; Janelidze, Shorena LU ; Hansson, Oskar LU orcid and Puschmann, Andreas LU orcid (2022) In Journal of Parkinson's Disease 12(2). p.571-584
Abstract

Background: Biochemical and clinical biomarkers correlate with progression rate and disease severity in Parkinson's disease (PD) but are not sufficiently studied in late PD. Objective: To examine how serum neurofilament light chain (S-NfL) alone or combined with clinical classifications predicts PD outcome in later disease stages. Methods: Eighty-five patients with 7.9±5.1 years of PD duration were included in an observational cohort. Clinical scores were obtained at two separate examinations 8.2±2.0 years apart. S-NfL levels were determined with single molecule array (SiMoA). Five predefined disease progression milestones were assessed. After affirming combination potential of S-NfL and either of two clinical classifications, three... (More)

Background: Biochemical and clinical biomarkers correlate with progression rate and disease severity in Parkinson's disease (PD) but are not sufficiently studied in late PD. Objective: To examine how serum neurofilament light chain (S-NfL) alone or combined with clinical classifications predicts PD outcome in later disease stages. Methods: Eighty-five patients with 7.9±5.1 years of PD duration were included in an observational cohort. Clinical scores were obtained at two separate examinations 8.2±2.0 years apart. S-NfL levels were determined with single molecule array (SiMoA). Five predefined disease progression milestones were assessed. After affirming combination potential of S-NfL and either of two clinical classifications, three combined models were constructed based on these factors and age at onset in different combinations. Results: S-NfL levels showed significant hazard ratios for four out of five disease progression milestones: walking-aid usage (HR 3.5; 95% CI 1.4-8.5), nursing home living (5.1; 2.1-12.5), motor end-stage (6.2; 2.1-17.8), and death (4.1; 1.7-9.7). Higher S-NfL levels were associated with lower ability in activities of daily living and poorer cognition at baseline and/or at follow-up. Combined models showed significantly improved area under receiver operating characteristic curves (0.77-0.91) compared to S-NfL levels alone (0.68-0.71) for predicting the five disease milestones. Conclusion: S-NfL levels stratified patients according to their likelihood to reach clinically relevant progression milestones during this long-term observational study. S-NfL alone reflected motor and social outcomes in later stages of PD. Combining S-NfL with clinical factors was possible and exploratory combined models improved prognostic accuracy.

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Please use this url to cite or link to this publication:
author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
biomarkers, dementia, mortality, neurofilament proteins, Parkinson's disease, prognosis
in
Journal of Parkinson's Disease
volume
12
issue
2
pages
14 pages
publisher
IOS Press
external identifiers
  • scopus:85125000117
  • pmid:34806619
ISSN
1877-7171
DOI
10.3233/JPD-212866
language
English
LU publication?
yes
id
240aa12b-58e9-46da-8da1-333f63125502
date added to LUP
2022-04-12 15:48:12
date last changed
2024-06-17 00:17:52
@article{240aa12b-58e9-46da-8da1-333f63125502,
  abstract     = {{<p>Background: Biochemical and clinical biomarkers correlate with progression rate and disease severity in Parkinson's disease (PD) but are not sufficiently studied in late PD. Objective: To examine how serum neurofilament light chain (S-NfL) alone or combined with clinical classifications predicts PD outcome in later disease stages. Methods: Eighty-five patients with 7.9±5.1 years of PD duration were included in an observational cohort. Clinical scores were obtained at two separate examinations 8.2±2.0 years apart. S-NfL levels were determined with single molecule array (SiMoA). Five predefined disease progression milestones were assessed. After affirming combination potential of S-NfL and either of two clinical classifications, three combined models were constructed based on these factors and age at onset in different combinations. Results: S-NfL levels showed significant hazard ratios for four out of five disease progression milestones: walking-aid usage (HR 3.5; 95% CI 1.4-8.5), nursing home living (5.1; 2.1-12.5), motor end-stage (6.2; 2.1-17.8), and death (4.1; 1.7-9.7). Higher S-NfL levels were associated with lower ability in activities of daily living and poorer cognition at baseline and/or at follow-up. Combined models showed significantly improved area under receiver operating characteristic curves (0.77-0.91) compared to S-NfL levels alone (0.68-0.71) for predicting the five disease milestones. Conclusion: S-NfL levels stratified patients according to their likelihood to reach clinically relevant progression milestones during this long-term observational study. S-NfL alone reflected motor and social outcomes in later stages of PD. Combining S-NfL with clinical factors was possible and exploratory combined models improved prognostic accuracy.</p>}},
  author       = {{Ygland Rödström, Emil and Mattsson-Carlgren, Niklas and Janelidze, Shorena and Hansson, Oskar and Puschmann, Andreas}},
  issn         = {{1877-7171}},
  keywords     = {{biomarkers; dementia; mortality; neurofilament proteins; Parkinson's disease; prognosis}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{571--584}},
  publisher    = {{IOS Press}},
  series       = {{Journal of Parkinson's Disease}},
  title        = {{Serum Neurofilament Light Chain as a Marker of Progression in Parkinson's Disease : Long-Term Observation and Implications of Clinical Subtypes}},
  url          = {{http://dx.doi.org/10.3233/JPD-212866}},
  doi          = {{10.3233/JPD-212866}},
  volume       = {{12}},
  year         = {{2022}},
}