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Serum p-tau217 is a prognostic indicator of cognitive impairment in idiopathic REM sleep behavior disorder

Abstract:

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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Publisher copy:
10.1002/ana.78109

Authors

More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Clinical Neurosciences
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Clinical Neurosciences
Role:
Author


More from this funder
Funder identifier:
https://ror.org/03x94j517
Grant:
MR/V007068/1
MR/Y019415/1
More from this funder
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:
1531-8249
ISSN:
0364-5134


Language:
English
Keywords:
Pubs id:
2336859
UUID:
uuid_2ec6af01-2524-4fed-a899-8365e542beb1
Local pid:
pubs:2336859
Source identifiers:
W4416784668
Deposit date:
2025-11-28
ARK identifier:

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