Background Excessive daytime sleepiness (EDS) is one of the most frequent non-motor symptoms in Parkinson's disease (PD); however, the pathogenesis of EDS is unclear, and there is a lack of information on plasma biomarkers for EDS in PD. We aimed to investigate the plasma biomarkers of EDS in a large PD cohort. Methods A total of 159 PD patients were included in the prospective cohort study and followed up annually for three years. Plasma biomarkers including glial fibrillary acidic protein, amyloid-beta, p-tau181, and neurofilament light chain (NfL), were measured using an ultrasensitive single-molecule array (SimoaTM) technology at each visit. EDS was evaluated using the Epworth Sleepiness Scale (ESS). Results The frequency of EDS in PD increased from 15.1% at baseline to 25.0% after three years. The mean ESS scores increased from 5.1 [Standard Deviation (SD): 4.8] at baseline to 6.1 [SD: 5.5] at the third year of follow-up. At baseline, compared with patients with PD without EDS, those with EDS were more likely to be male, had poorer cognitive performance, and more severe motor and non-motor symptoms. The adjusted generalized estimating equations models showed that higher plasma NfL levels (OR 1.047 [1.002-1.094], p = 0.042) were associated with EDS during follow-ups. The adjusted linear mixed-effects model showed that higher plasma NfL levels (β 0.097 [0.012–0.183], p = 0.026) were associated with ESS scores during follow-ups. Conclusions Higher plasma NfL levels were associated with EDS in PD, indicating an association between neuro-axonal degeneration and EDS in PD.

中文翻译：

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帕金森病白天过度嗜睡的纵向进化和血浆生物标志物

背景 白天过度嗜睡 (EDS) 是帕金森病 (PD) 最常见的非运动症状之一；然而，EDS的发病机制尚不清楚，并且缺乏有关PD中EDS的血浆生物标志物的信息。我们的目的是在大型 PD 队列中研究 EDS 的血浆生物标志物。方法 前瞻性队列研究纳入159例PD患者，每年随访3年。每次访视时均使用超灵敏单分子阵列 (SimoaTM) 技术测量血浆生物标志物，包括神经胶质原纤维酸性蛋白、β-淀粉样蛋白、p-tau181 和神经丝轻链 (NfL)。 EDS 使用 Epworth 嗜睡量表 (ESS) 进行评估。结果 PD 中的 EDS 频率从基线时的 15.1% 增加到三年后的 25.0%。平均 ESS 评分从基线时的 5.1 [标准差 (SD)：4.8] 增加到随访第三年的 6.1 [SD：5.5]。在基线时，与没有 EDS 的 PD 患者相比，患有 EDS 的患者更有可能是男性，认知能力较差，运动和非运动症状更严重。调整后的广义估计方程模型显示，较高的血浆 NfL 水平（OR 1.047 [1.002-1.094]，p = 0.042）与随访期间的 EDS 相关。调整后的线性混合效应模型显示，较高的血浆 NfL 水平（β 0.097 [0.012–0.183]，p = 0.026）与随访期间的 ESS 评分相关。结论 较高的血浆 NfL 水平与 PD 中的 EDS 相关，表明神经轴突变性与 PD 中的 EDS 之间存在关联。