RESEARCHERS have identified p-tau217 as a powerful prognostic marker for cognitive impairment in people with idiopathic REM sleep behaviour disorder, a condition strongly linked to future neurodegenerative disease.
Why p-tau217 Matters in Idiopathic REM Sleep Behaviour Disorder
Idiopathic REM sleep behaviour disorder is widely recognised as a prodromal stage of synucleinopathies such as Parkinson’s disease and dementia with Lewy bodies. However, predicting which individuals will develop cognitive impairment remains challenging. The identification of p-tau217 as a blood-based biomarker offers a potential way to stratify risk earlier, reflecting underlying Alzheimer type co pathology that may influence cognitive trajectories in this population.
p-tau217 Performance Across Cohorts
This retrospective cross-sectional study analysed serum samples from four polysomnographically confirmed cohorts of individuals with idiopathic REM sleep behaviour disorder. A total of 300 participants were included, with recruitment spanning July 2013 to February 2024 and biomarker analysis completed between May 2024 and April 2025. Among 307 participants analysed, the mean age was 66.59 years with 268 men and 39 women.
Phenoconversion occurred to Parkinson’s disease in 51 individuals, dementia with Lewy bodies in 22, and multiple system atrophy in five. Serum p-tau217 levels were higher in participants with cognitive impairment defined by Montreal Cognitive Assessment scores below 26. p-tau217 differentiated those who developed Parkinson’s disease with cognitive impairment or dementia with Lewy bodies from Parkinson’s disease phenoconverters with normal cognition, with an area under the curve of 0.82 and a 95% confidence interval from 0.70 to 0.93. Similar discrimination was seen versus non phenoconverters with normal cognition, with an area under the curve of 0.83 and a 95% confidence interval from 0.77 to 0.89. Individuals in the top quartile of p-tau217 were eight times more likely to phenoconvert to dementia phenotypes, with a hazard ratio of 8.30 and a 95% confidence interval from 2.49 to 27.65. Neurofilament light chain added minimal predictive value.
Implications For Clinical Practice
These findings position p-tau217 as a clinically relevant biomarker for identifying patients with idiopathic REM sleep behaviour disorder who are at heightened risk of cognitive decline or dementia. Incorporating p-tau217 into multimodal prognostic models could support earlier counselling, monitoring, and enrolment into targeted clinical trials, moving practice closer to personalised risk stratification.
Reference
Yan S et al. Serum p‐tau217 is a prognostic indicator of cognitive impairment in idiopathic REM sleep behavior disorder. ANN NEUROL. 2025;DOI:10.1002/ana.78109.
