Department of Neurology, Tianjin Medical University General Hospital Airport Site, Tianjin, China.
Department of Neurology, Tianjin Medical University General Hospital, Tianjin, China.
J Parkinsons Dis. 2023;13(4):485-499. doi: 10.3233/JPD-223519.
Idiopathic rapid eye movement sleep behavior disorder (iRBD) is increasingly recognized as a manifestation preceding the α-synucleinopathies like Parkinson's disease (PD). Neurofilament light chain (NfL) have been reported to be higher in synucleinopathies as a sign of neurodegeneration.
To evaluate whether plasma NfL is valuable in reflecting cognitive and motor status in iRBD and PD with a premorbid history of RBD (PDRBD), and predicting disease progression in iRBD.
Thirty-one patients with iRBD, 30 with PDRBD, and 18 healthy controls were included in the cross-sectional and prospective study. Another cohort from the Parkinson's Progression Markers Initiative (PPMI) dataset was enrolled for verification analysis. All patients received evaluations of cognitive, motor, and autonomic function by a battery of clinical tests at baseline and follow-up. Blood NfL was measured by the Quanterix Simoa HD-1.
In our cohort, 26 patients with iRBD completed the follow-up evaluations, among whom eight (30.8%) patients displayed phenoconversion. Baseline plasma NfL cutoff value of 22.93 pg/mL performed best in distinguishing the iRBD converters from non-converters (sensitivity: 75.0%, specificity: 83.3%, area under the curve: 0.84). Cognitive and motor function were significantly correlated with NfL levels in PDRBD (correlation coefficients: -0.379, 0.399; respectively). Higher baseline NfL levels in iRBD were significantly associated with higher risks for cognitive, motor, autonomic function progression, and phenoconversion at follow-up (hazard ratios: 1.069, 1.065, 1.170, 1.065; respectively). The findings were supported by the PPMI dataset.
Plasma NfL is valuable in reflecting disease severity of PDRBD and predicting disease progression and phenoconversion in iRBD.
特发性快速眼动睡眠行为障碍（iRBD）越来越被认为是一种类似于帕金森病（PD）的α-突触核蛋白病的表现前状态。神经丝轻链（NfL）在突触核蛋白病中较高，作为神经退行性变的标志。
评估血浆 NfL 是否可用于反映有快速眼动睡眠行为障碍（iRBD）和有快速眼动睡眠行为障碍前期史（PDRBD）的 PD 患者的认知和运动状态，并预测 iRBD 患者的疾病进展。
纳入 31 例 iRBD 患者、30 例 PDRBD 患者和 18 名健康对照者进行横断面和前瞻性研究。另一个队列来自帕金森病进展标志物倡议（PPMI）数据集，用于验证分析。所有患者在基线和随访时接受一系列临床测试评估认知、运动和自主功能。通过 Quanterix Simoa HD-1 测量血液 NfL。
在我们的队列中，26 例 iRBD 患者完成了随访评估，其中 8 例（30.8%）患者出现了表型转化。基线血浆 NfL 截断值 22.93pg/mL 可最佳区分 iRBD 转化者与非转化者（灵敏度：75.0%，特异性：83.3%，曲线下面积：0.84）。在 PDRBD 中，认知和运动功能与 NfL 水平显著相关（相关系数：-0.379，0.399；分别）。iRBD 患者较高的基线 NfL 水平与随访时认知、运动、自主功能进展和表型转化的风险显著相关（风险比：1.069，1.065，1.170，1.065；分别）。这些发现得到了 PPMI 数据集的支持。
血浆 NfL 可用于反映 PDRBD 的疾病严重程度，并预测 iRBD 患者的疾病进展和表型转化。
