Fully-automated sleep staging: multicenter validation of a generalizable deep neural network for Parkinson's disease and isolated REM sleep behavior disorder

Isolated REM sleep behavior disorder (iRBD) is a key prodromal marker of Parkinson's disease (PD), and video-polysomnography (vPSG) remains the diagnostic gold standard. However, manual sleep staging is particularly challenging in neurodegenerative diseases due to EEG abnormalities and fragmented sleep, making PSG assessments a bottleneck for deploying new RBD screening technologies at scale. We adapted U-Sleep, a deep neural network, for generalizable sleep staging in PD and iRBD. A pretrained U-Sleep model, based on a large, multisite non-neurodegenerative dataset (PUB; 19,236 PSGs across 12 sites), was fine-tuned on research datasets from two centers (Lundbeck Foundation Parkinson's Disease Research Center (PACE) and the Cologne-Bonn Cohort (CBC); 112 PD, 138 iRBD, 89 age-matched controls. The resulting model was evaluated on an independent dataset from the Danish Center for Sleep Medicine (DCSM; 81 PD, 36 iRBD, 87 sleep-clinic controls). A subset of PSGs with low agreement between the human rater and the model (Cohen's $κ$ < 0.6) was re-scored by a second blinded human rater to identify sources of disagreement. Finally, we applied confidence-based thresholds to optimize REM sleep staging. The pretrained model achieved mean $κ$ = 0.81 in PUB, but $κ$ = 0.66 when applied directly to PACE/CBC. By fine-tuning the model, we developed a generalized model with $κ$ = 0.74 on PACE/CBC (p < 0.001 vs. the pretrained model). In DCSM, mean and median $κ$ increased from 0.60 to 0.64 (p < 0.001) and 0.64 to 0.69 (p < 0.001), respectively. In the interrater study, PSGs with low agreement between the model and the initial scorer showed similarly low agreement between human scorers. Applying a confidence threshold increased the proportion of correctly identified REM sleep epochs from 85% to 95.5%, while preserving sufficient (> 5 min) REM sleep for 95% of subjects.

ActiTect: A Generalizable Machine Learning Pipeline for REM Sleep Behavior Disorder Screening through Standardized Actigraphy

Isolated rapid eye movement sleep behavior disorder (iRBD) is a major prodromal marker of $α$-synucleinopathies, often preceding the clinical onset of Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy. While wrist-worn actimeters hold significant potential for detecting RBD in large-scale screening efforts by capturing abnormal nocturnal movements, they become inoperable without a reliable and efficient analysis pipeline. This study presents ActiTect, a fully automated, open-source machine learning tool to identify RBD from actigraphy recordings. To ensure generalizability across heterogeneous acquisition settings, our pipeline includes robust preprocessing and automated sleep-wake detection to harmonize multi-device data and extract physiologically interpretable motion features characterizing activity patterns. Model development was conducted on a cohort of 78 individuals, yielding strong discrimination under nested cross-validation (AUROC = 0.95). Generalization was confirmed on a blinded local test set (n = 31, AUROC = 0.86) and on two independent external cohorts (n = 113, AUROC = 0.84; n = 57, AUROC = 0.94). To assess real-world robustness, leave-one-dataset-out cross-validation across the internal and external cohorts demonstrated consistent performance (AUROC range = 0.84-0.89). A complementary stability analysis showed that key predictive features remained reproducible across datasets, supporting the final pooled multi-center model as a robust pre-trained resource for broader deployment. By being open-source and easy to use, our tool promotes widespread adoption and facilitates independent validation and collaborative improvements, thereby advancing the field toward a unified and generalizable RBD detection model using wearable devices.