Journal article
Serum p-tau217 is a prognostic indicator of cognitive impairment in idiopathic REM sleep behavior disorder
- Abstract:
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Objective: Assess the performance of serum phosphorylated tau 217 (p-tau217) and neurofilament light chain (NfL) in predicting risk of cognitive impairment or phenoconversion to dementia in individuals with iRBD.
Methods: We measured serum p-tau217 and NfL levels by electrochemiluminescence across 4 polysomnographically confirmed iRBD cohorts (n = 300), including individuals who phenoconverted to Parkinson's disease (PD) (n = 51), dementia with Lewy bodies (DLB) (n = 22), and multiple system atrophy (MSA) (n = 5).
Results: Serum p-tau217 levels were increased in individuals with iRBD and cognitive impairment (CI) on testing defined as Montreal Cognitive Assessment <26 or subthreshold parkinsonism. p-Tau217 differentiated individuals with iRBD who developed PD with CI (PD-CI) or DLB from PD phenoconverters with normal cognition (area under curve [AUC] = 0.82; 95% confidence interval, 0.70–0.93) and from iRBD non-phenoconverters with normal cognition (AUC = 0.83; 95% confidence interval, 0.77–0.89). NfL levels did not correlate with cognitive or motor scores and marginally improved p-tau217 performance (AUC = 0.85; 95% confidence interval, 0.78–0.92), but were notably elevated in iRBD individuals who phenoconverted to MSA. Individuals with p-tau217 in the top quartile were 8 times more likely to phenoconvert to PD-CI or DLB compared to the bottom quartile (hazard ratio = 8.30; 95% confidence interval, 2.49–27.65).
Interpretation: Serum p-tau217, but not NfL, is a useful biomarker of cognitive impairment in iRBD that could be integrated into a multimodal prognostic indicator when stratifying risk of phenoconversion.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 888.2KB, Terms of use)
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- Publisher copy:
- 10.1002/ana.78109
Authors
- Funder identifier:
- https://ror.org/03x94j517
- Grant:
- MR/V007068/1
- MR/Y019415/1
- Funder identifier:
- https://ror.org/03arq3225
- Grant:
- MJFF-025283
- Publisher:
- Wiley
- Journal:
- Annals of Neurology More from this journal
- Volume:
- 99
- Issue:
- 4
- Pages:
- 912-921
- Publication date:
- 2025-11-28
- Acceptance date:
- 2025-10-23
- DOI:
- EISSN:
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1531-8249
- ISSN:
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0364-5134
- Language:
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English
- Keywords:
- Pubs id:
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2336859
- UUID:
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uuid_2ec6af01-2524-4fed-a899-8365e542beb1
- Local pid:
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pubs:2336859
- Source identifiers:
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W4416784668
- Deposit date:
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2025-11-28
- ARK identifier:
Terms of use
- Copyright holder:
- Yan et al.
- Copyright date:
- 2025
- Rights statement:
- © 2025 The Author(s). Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Licence:
- CC Attribution (CC BY)
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