Journal Article DZNE-2025-01302

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Serum p‐tau217 Is a Prognostic Indicator of Cognitive Impairment in Idiopathic REM Sleep Behavior Disorder

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2025
Wiley-Blackwell Hoboken, NJ

Annals of neurology AOP, ana.78109 () [10.1002/ana.78109]

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Abstract: ObjectiveAssess 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.MethodsWe 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).ResultsSerum 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).InterpretationSerum 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. ANN NEUROL 2025

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Contributing Institute(s):
  1. Vascular Neurology (AG Petzold)
Research Program(s):
  1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

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 Record created 2025-12-01, last modified 2025-12-01