Leng Bing, Sun Hairong, Li Mengfan, Zhao Junwu, Liu Xiaoxiao, Yao Ran, Shen Tengqun, Li Zhenguang, Zhang Jinbiao
Department of Neurology, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, China.
Front Aging Neurosci. 2022 Aug 23;14:952368. doi: 10.3389/fnagi.2022.952368. eCollection 2022.
Rapid eye movement (REM) sleep behavior disorder (RBD) predicts cognitive decline in Parkinson's disease (PD) patients without dementia. However, underlying mechanisms remain unknown. Accumulating studies suggest glutamatergic system dysregulation is associated.
To examine the effect of RBD on the rate of cognitive decline in PD patients and investigate whether plasma levels of the neuroexosomal vesicular glutamate transporter-1 (VGLUT-1) and excitatory amino acid transporter-2 (EAAT-2) are altered in PD patients with RBD.
This study included 157 newly diagnosed cognitive normal PD patients and 70 healthy controls (HCs). Based on one-night polysomnography recordings, the PD subjects were divided into PD with and without RBD (PD-RBD and PD-nRBD) groups. All participants received a complete clinical and neuropsychological evaluation at baseline. Plasma levels of neuroexosomal VGLUT-1 and EAAT-2 were measured by ELISA kits. After a 3-year follow-up, we evaluated baseline plasma levels of neuroexosomal glutamate transporters in each group as a predictor of cognitive decline using MoCA score changes over 3 years in regression models.
Plasma levels of neuron-derived exosomal EAAT-2 and VGLUT-1 were significantly lower in PD patients than in HCs. Plasma levels of neuroexosomal EAAT-2 were significantly lower in PD-RBD than PD-nRBD group at baseline. At the 3-year follow-up, PD-RBD patients presented greater cognitive decline. Lower baseline blood neuroexosomal EAAT-2 predicted cognitive decline over 3 years in PD-RBD patients (β = 0.064, = 0.003).
These findings indicate that blood neuroexosomal EAAT-2 is associated with cognitive decline in PD with RBD.
快速眼动（REM）睡眠行为障碍（RBD）可预测无痴呆帕金森病（PD）患者的认知功能下降。然而，其潜在机制仍不清楚。越来越多的研究表明，谷氨酸能系统失调与之相关。
研究RBD对PD患者认知功能下降速度的影响，并调查RBD的PD患者血浆中神经外泌体囊泡谷氨酸转运体1（VGLUT-1）和兴奋性氨基酸转运体2（EAAT-2）水平是否发生改变。
本研究纳入157例新诊断的认知功能正常的PD患者和70例健康对照（HCs）。根据一晚的多导睡眠图记录，将PD受试者分为有RBD和无RBD的PD组（PD-RBD和PD-nRBD）。所有参与者在基线时接受了完整的临床和神经心理学评估。用ELISA试剂盒检测血浆中神经外泌体VGLUT-1和EAAT-2的水平。经过3年的随访，我们在回归模型中使用3年期间的蒙特利尔认知评估量表（MoCA）评分变化，将每组神经外泌体谷氨酸转运体的基线血浆水平评估为认知功能下降的预测指标。
PD患者神经元来源的外泌体EAAT-2和VGLUT-1的血浆水平显著低于HCs。基线时，PD-RBD组神经外泌体EAAT-2的血浆水平显著低于PD-nRBD组。在3年随访时，PD-RBD患者出现了更大程度的认知功能下降。较低的基线血液神经外泌体EAAT-2水平可预测PD-RBD患者3年内的认知功能下降（β = 0.064，P = 0.003）。
这些发现表明，血液神经外泌体EAAT-2与RBD的PD患者的认知功能下降有关。
