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 aggregates in Parkinson's disease has not been well investigated. The aim of this study was to reveal the relationship between misfolded α-synuclein aggregate concentration in cerebrospinal fluid and cognitive decline risk in Parkinson's disease.

METHODS: A total of 278 patients with Parkinson's disease 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-synuclein aggregate concentration in baseline cerebrospinal fluid was measured using the protein misfolding cyclic amplification technique. Time to reach 50% of the maximum fluorescence value was recorded.

RESULTS: The protein misfolding cyclic amplification technique successfully detected the level of misfolded α-synuclein aggregates in cerebrospinal fluid 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 hours vs. 240.8 ± 45.6 hours, P < 0.001). Multifactorial Cox regression analysis revealed that reaching 50% of the maximum fluorescence value in ≤ 219 hours 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-synuclein aggregates in cerebrospinal fluid measured by the protein misfolding cyclic amplification technique predicts risk of cognitive decline in Parkinson's disease. This article is protected by copyright. All rights reserved.