Abstract
BACKGROUND: Rapid eye movement sleep behavior disorder (RBD) is associated with cognitive decline in early Parkinson's disease (PD). However, the underlyling basis for this association remains unclear. METHODS: Parkinson's Progression Marker's Initiative (PPMI) subjects underwent baseline RBD testing with RBD sleep questionnaire (RBDSQ). Serial assessments included measures of motor symptoms, non-motor symptoms (NMS), neuropsychological assessment, blood and cerebrospinal fluid (CSF) biomarkers. Up to three years follow-up data were included. We stratified early PD subjects into PD with RBD (RBDSQ score > 5) and PD without RBD groups. Then, we evaluated baseline biomarkers in each group as a predictor of cognitive decline using Montreal Cognitive Assessment (MoCA) score changes over three years in regression models. RESULTS: Four hundred twenty-three PD subjects were enrolled at baseline, and a total of 350 PD subjects had completed 3 years of study follow-up with completely serial assessments. We found that at baseline, only CSF β-amyloid 1-42 (Aβ(1-42)) was significantly lower in PD subjects with RBD. On three years follow-up analysis, PD subjects with RBD were more likely to develop incident mild cognitive impairment (MCI) and presented greater cognitive decline in MoCA score. Lower baseline CSF Aβ(1-42) predicted cognitive decline over 3 years only in PD subjects with RBD (β = - 0.03, P = 0.003). A significant interaction between Aβ(1-42) and the 2 groups confirmed that this effect was indeed higher in PD with RBD than the other individual (β = - 2.85, P = 0.014). CONCLUSION: These findings indicate that CSF Aβ(1-42) level is associated with global cognitive decline in early PD with RBD. The addition of CSF Aβ(1-42) to RBD testing increase the likelihood of identifying those at high risk for cognitive decline in early PD.