Higher Glymphatic System Activity Is Linked to Longer Prodromal Stage in Isolated REM Sleep Behavior Disorder: A Possible Protective Factor

Isolated rapid eye movement sleep behavior disorder (iRBD) is commonly recognized as a prodromal stage of alpha-synucleinopathies. Dysfunction of glymphatic system was previously investigated in Parkinson’s disease, however in iRBD it has been understudied to this date. This study aimed to evaluate the association between the glymphatic function and the duration of RBD symptoms, to investigate the predictive effect and speed modulating effect to alpha-synucleionpathy conversion.Fifty-six patients (67.2 ± 7.1 [mean age ± SD]) with an iRBD diagnosis confirmed by polysomnography underwent magnetic resonance imaging of the brain. Glymphatic function was evaluated using the diffusion tensor imaging along the perivascular space (DTI-ALPS) method with manual acquisition of the ALPS-index.We identified a positive correlation between the ALPS-index and the duration of iRBD symptoms (rho = 0.409, p = 0.002). Although ALPS-index did not show significant predictive effect to conversion in the whole group, among the patients who eventually converted, patients with higher ALPS-index exhibited more than nine years longer time to conversion than patients with lower ALPS-index (χ² = 13.075, p < 0.001).We imply that the glymphatic system may serve as a protective factor, preserving the prodromal stage of the disease, and slowing the clinical conversion.