Tao Mingzhu, Dou Kaixin, Xie Yijie, Hou Binghui, Xie Anmu
Department of Neurology, Affiliated Hospital of Qingdao University, Qingdao, China.
Department of Clinical Laboratory, Affiliated Hospital of Qingdao University, Qingdao, China.
Front Neurosci. 2022 Nov 23;16:1049118. doi: 10.3389/fnins.2022.1049118. eCollection 2022.
In Parkinson's disease (PD), levels of cerebrospinal fluid (CSF) biomarkers and progression of non-motor symptoms are associated, but the specifics are not yet clear.
The aim of this study was to investigate the associations of non-motor symptoms with CSF biomarkers in PD.
We assessed 487 individuals from the Parkinson's Progression Markers Initiative (PPMI), consisting of 155 healthy controls (HCs) and 332 individuals with PD. Patients with PD were grouped according to non-motor symptoms and compared CSF α-synuclein (α-syn), amyloid-beta 1-42 (Aβ), and total tau (t-tau) levels. Multiple linear regressions were used in baseline analysis and linear mixed-effects models in longitudinal analysis. Analyses of mediating effects between cognition and CSF biomarkers were also performed.
At baseline, PD patients with cognitive impairment (PDCI) exhibited significantly lower CSF α-syn (β = -0.1244; = 0.0469), Aβ (β = -0.1302; = 0.0447), and t-tau (β = -0.1260; = 0.0131) levels than PD patients without cognitive impairment (PDCU). Moreover, a faster decline of α-syn (β = -0.2152; = 0.0374) and Aβ (β = -0.3114; = 0.0023) and a faster rise of t-tau (β = -0.1534; = 0.0274) have been found in longitudinal analysis. The Aβ positive group showed an earlier decline in cognitive performance (β = -0.5341; = 0.0180) compared with the negative Aβ group in both analyses. In addition, we found that PD patients with probable rapid eye movement sleep behavior disorder (pRBD) showed decreased CSF α-syn (β = -0.1343; = 0.0033) levels. Finally, mediation analysis demonstrated that olfactory function partially mediated the relationship between cognition and CSF biomarkers levels.
Our study shows that CSF biomarkers are associated with cognition at baseline and longitudinally. Cognitive impairment is more severe in patients with a heavier Aβ burden. CSF α-syn decreased in PD patients with pRBD. This study suggests that early recognition of the increased risk of non-motor symptoms is important for disease surveillance and may be associated with the pathological progression of CSF markers.
在帕金森病（PD）中，脑脊液（CSF）生物标志物水平与非运动症状的进展相关，但具体情况尚不清楚。
本研究旨在探讨PD中非运动症状与CSF生物标志物之间的关联。
我们评估了帕金森病进展标志物计划（PPMI）中的487名个体，其中包括155名健康对照（HC）和332名PD患者。根据非运动症状对PD患者进行分组，并比较CSF中α-突触核蛋白（α-syn）、淀粉样β蛋白1-42（Aβ）和总tau蛋白（t-tau）水平。基线分析采用多元线性回归，纵向分析采用线性混合效应模型。还进行了认知与CSF生物标志物之间中介效应的分析。
在基线时，有认知障碍的PD患者（PDCI）的CSF中α-syn（β = -0.1244；P = 0.0469）、Aβ（β = -0.1302；P = 0.0447）和t-tau（β = -0.1260；P = 0.0131）水平显著低于无认知障碍的PD患者（PDCU）。此外，纵向分析发现α-syn（β = -0.2152；P = 0.0374）和Aβ（β = -0.3114；P = 0.0023）下降更快，t-tau（β = -0.1534；P = 0.0274）上升更快。在两项分析中，Aβ阳性组的认知表现下降早于Aβ阴性组（β = -0.5341；P = 0.0180）。此外，我们发现可能患有快速眼动睡眠行为障碍（pRBD）的PD患者CSF中α-syn水平降低（β = -0.1343；P = 0.0033）。最后，中介分析表明嗅觉功能部分介导了认知与CSF生物标志物水平之间的关系。
我们的研究表明，CSF生物标志物在基线和纵向都与认知相关。Aβ负担较重的患者认知障碍更严重。pRBD的PD患者CSF中α-syn降低。本研究表明，早期识别非运动症状风险增加对疾病监测很重要，且可能与CSF标志物的病理进展相关。
