CSF Aβ(1–42) level is associated with cognitive decline in early Parkinson’s disease with rapid eye movement sleep behavior disorder

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.