The presence or absence of clinically probable RBD (pRBD) was screened through medical record review of patients in our brain bank from 1998 to 2023. When available, polysomnography (PSG) confirmed RBD was included. Clinical and pathological diagnoses were compared between patients with and without RBD.

We identified 1,391 patients (36% female, age at death 72.9±9.0 years) with RBD documentation, of whom, 728 (52%) had pRBD. A pathologic diagnosis of α-synucleinopathy was 7 times more likely in those with pRBD (78% of 728) than in those without RBD (32% of 663; odds ratio: 7.4 [95%CI: 5.9-9.5]; P<0.0001). In the 22% (160/728) of pRBD patients without α-synuclein pathology, tauopathies were most common (60 progressive supranuclear palsy, 18 corticobasal degeneration, and 23 Alzheimer's disease). In those without α-synuclein pathology, a clinical diagnosis including α-synucleinopathy was more frequent in those with pRBD compared to those without pRBD (33% vs 13%; P<0.0001). PSG was conducted in 150 of 1,391 patients, of whom 18 did not achieve REM sleep, and 38% (50/132) had PSG-confirmed RBD. Those with PSG-confirmed RBD (86% of 50) were nearly 5 times more likely to have α-synuclein pathology than those without it (56% of 82; odds ratio: 4.8 [1.9-11.9]; P=0.0005). Of the 7 patients with PSG-confirmed RBD lacking α-synuclein pathology, 3 had progressive supranuclear palsy.