Self-Reported REM Sleep Behavior Disorder in Patients With Progressive Supranuclear Palsy: Clinical and F-Florzolotau PET Imaging Findings.

Background And Objectives: Rapid eye movement sleep behavior disorder (RBD) is increasingly recognized in patients with tauopathies, but its significance and underpinnings remain unclear. To address this gap, we investigated the prevalence of self-reported RBD in patients with progressive supranuclear palsy (PSP) and explored its clinical and imaging correlates using F-florzolotau PET imaging.

Methods: We consecutively enrolled patients meeting the 2017 Movement Disorder Society clinical criteria for PSP at a Chinese tertiary hospital between May 2019 and March 2022. Patients underwent comprehensive clinical assessments and F-florzolotau PET to investigate tau deposition patterns. The presence of self-reported RBD was identified using the RBD Single-Question Screen, while its frequency was retrospectively collected from medical history.

Results: We examined 148 patients recruited in the ongoing Progressive Supranuclear Palsy Neuroimage Initiative cohort. Self-reported RBD was identified in 18.2% of the participants (27/148). Patients with PSP-Richardson syndrome and PSP-parkinsonism reported the highest frequencies of self-reported RBD (21.7% and 18.5%, respectively), compared with PSP-progressive gait freezing (9.7%). While age and sex were similar in patients with and without self-reported RBD, the former group exhibited greater disease severity, as indicated by higher PSP Rating Scale (PSPrs) scores (38.0 vs 27.0, effect size = 0.256, = 0.002). Furthermore, patients with RBD had significantly higher F-florzolotau binding in the locus coeruleus (LC) (1.50 vs 1.38, effect size = 0.231, = 0.003), which remained significant after false discovery rate correction ( = 0.042). The frequency of RBD was found to be correlated with tau pathology in the LC (n = 8, = 0.752, = 0.002). Notably, the presence of self-reported RBD symptoms mediated the relationship between LC tau pathology and PSPrs total scores (proportion-mediated = 2.09%, 95% CI 0.01%-10.00%, = 0.044).

Discussion: Approximately one-fifth of patients with PSP reported RBD and exhibited more severe motor and nonmotor symptoms. The elevated F-florzolotau binding in the LC and its association with the presence of RBD symptoms underscore the critical role of tau pathology in disrupting sleep-regulating neural circuits. Future studies with larger sample sizes should incorporate polysomnography in patients with PSP with self-reported RBD to further elucidate this relationship.