Baseline concentration of misfolded α‐synuclein aggregates in cerebrospinal fluid predicts risk of cognitive decline in Parkinson's disease

BACKGROUND: The prognostic significance of misfolded α‐synuclein (α‐Syn) aggregates in Parkinson's disease (PD) has not been well investigated. The aim of this study was to reveal the relationship between misfolded α‐Syn aggregate concentration in cerebrospinal fluid (CSF) and cognitive decline risk in PD. METHODS: A total of 278 patients with PD were retrospectively included. They were diagnosed between 2011 and 2013. The end‐point was 2016, and the follow‐up period was 54.3 ± 10.0 months. Cognitive decline was defined as a 4‐point decrease in the Mini‐Mental State Examination score during follow‐up. Misfolded α‐Syn aggregate concentration in baseline CSF was measured using the protein misfolding cyclic amplification (PMCA) technique. Time to reach 50% of the maximum fluorescence value was recorded. RESULTS: The PMCA technique successfully detected the level of misfolded α‐Syn aggregates in CSF with a sensitivity of 85.3% and a specificity of 91.4%. The time to reach 50% of the maximum fluorescence value was shorter in the patients with cognitive decline than in the patients without cognitive decline (190.7 ± 40.1 h vs. 240.8 ± 45.6 h, P < 0.001). Multifactorial Cox regression analysis revealed that reaching 50% of the maximum fluorescence value in ≤219 h at baseline was associated with increased risk of cognitive decline during the follow‐up (HR: 4.90, 95% CI: 2.75–8.74, P < 0.001). CONCLUSION: Baseline concentration of misfolded α‐Syn aggregates in CSF measured by the PMCA technique predicts risk of cognitive decline in PD.