REM behavior disorder predicts motor progression and cognitive decline in Parkinson disease

Objective To investigate whether REM sleep behavior disorder (RBD) is associated with worse motor and cognitive decline in Parkinson disease (PD) Methods Four-hundred twenty-one drug-naive patients with early-stage PD and 196 controls without PD were included in this study. All participants underwent a [I-123] FP-CIT SPECT scan, CSF assessment, 3-tesla MRI, and thorough clinical assessments. Results At cross-sectional analyses, patients with PD and probable RBD (PD-RBD) had lower CSF beta-amyloid 1-42 (A beta 42) levels and higher total tau to A beta 42 CSF ratio, higher nonmotor symptoms burden, and worse scores on neuropsychological tests of processing speed, visuo-spatial functioning, and delayed recognition memory compared to patients with PD without RBD. At longitudinal analyses, the presence of RBD was associated with faster motor progression (hazard ratio [HR] = 1.368, 95% confidence Interval [CI] = 1.036-1.806; p = 0.027) and cognitive decline (HR = 1.794, 95% CI = 1.163-2.768; p = 0.008) over 60-month follow-up. The presence of RBD was a predictor for motor progression only in patients with PD who had both low a-synuclein levels and low [I-123] FP-CIT uptake in the striatum (HR = 2.091, 95% CI = 1.116-3.918; p = 0.021) and a predictor for cognitive decline only in patients with PD who had both low A beta 42 and low a-synuclein levels (HR = 2.810, 95% CI = 1.462-5.400; p = 0.002). In the population of controls without PD, the presence of RBD was not associated with cognitive decline or any baseline pathologic changes. Conclusion The presence of RBD in PD is associated with faster motor progression in patients with greater synuclein and dopaminergic pathology, and with higher risk of cognitive decline in patients with greater synuclein and amyloid pathology. Our findings provide an important direction toward understanding phenotypes and their prognosis in PD.