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000282539 0247_ $$2doi$$a10.1002/ana.78109
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000282539 1001_ $$aYan, Shijun$$b0
000282539 245__ $$aSerum p‐tau217 Is a Prognostic Indicator of Cognitive Impairment in Idiopathic REM Sleep Behavior Disorder
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000282539 520__ $$aObjectiveAssess 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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000282539 7001_ $$aSahoo, Anis$$b1
000282539 7001_ $$aZerenner, Tanja$$b2
000282539 7001_ $$aMarek, Kenneth$$b3
000282539 7001_ $$0P:(DE-2719)9003277$$aSommerauer, Michael$$b4$$udzne
000282539 7001_ $$0P:(DE-2719)9000908$$aOertel, Wolfgang$$b5
000282539 7001_ $$aHu, Michele T.$$b6
000282539 7001_ $$00000-0002-9252-5933$$aTofaris, George K.$$b7
000282539 773__ $$0PERI:(DE-600)2037912-2$$a10.1002/ana.78109$$gp. ana.78109$$pana.78109$$tAnnals of neurology$$vAOP$$x0364-5134$$y2025
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