Chen Ying, Xue Nai-Jia, Fang Yi, Jin Chong-Yao, Li Yao-Lin, Tian Jun, Yan Ya-Ping, Yin Xin-Zhen, Zhang Bao-Rong, Pu Jia-Li
Department of Neurology, Second Affiliated Hospital, School of Medicine Zhejiang University Zhejiang China.
Mov Disord Clin Pract. 2022 Jul 22;9(7):909-919. doi: 10.1002/mdc3.13511. eCollection 2022 Oct.
Parkinson's disease (PD), with either rapid eye movement sleep behavior disorder (RBD) or olfactory dysfunction (OD), has been associated with disease progression. However, there is currently heterogeneity in predicting prognosis.
To identify whether the concurrent presence of OD and probable RBD (pRBD) in PD (Dual hit in PD, PD-DH) is associated with disease progression.
We included 420 patients with de novo PD from the Parkinson's Progression Markers Initiative: 180 PD only (PD), 82 PD with OD (PD-OD), 94 PD with pRBD (PD-pRBD), and 64 PD with both OD and pRBD (PD-DH). Participants underwent motor and nonmotor evaluations, dopamine transporter imaging, and cerebrospinal fluid (CSF) assessment. Data were analyzed with generalized estimating equations and Cox proportional hazards analysis.
The PD-DH subtype was associated with higher scores and faster progression rates in Movement Disorder Society-Unified PD Rating Scale (MDS-UPDRS) Parts II and III. Also, patients in PD-DH group had faster deterioration in nonmotor symptoms, including MDS-UPDRS Part I score, Montreal Cognitive Assessment, Hopkins Verbal Learning Test-Revised, Wechsler Memory Scale-Third edition (WMS-III) Letter Number Sequencing score, Symbol Digit Modalities Test, and Scales for Outcomes in PD-Autonomic scores, with all values <0.002. Moreover, the PD-DH subtype had a higher mild cognitive impairment risk (hazard ratio = 1.756, 95% confidence interval [CI] = 1.132-2.722; = 0.012), faster decline in caudate standard uptake values (β = -0.03, 95% CI = -0.06 to -0.008, = 0.012), and CSF α-synuclein levels (β = -77, 95% CI = -149 to -5, = 0.034) than the PD group.
Coexisting pRBD and OD in patients with PD may be associated with faster progressions in motor measurements and in cognitive and autonomic symptoms, indicating PD-DH as a more aggressive subtype for PD.
帕金森病（PD）伴有快速眼动睡眠行为障碍（RBD）或嗅觉功能障碍（OD）与疾病进展相关。然而，目前在预测预后方面存在异质性。
确定PD患者中OD与可能的RBD（pRBD）同时存在（PD双重打击，PD-DH）是否与疾病进展相关。
我们纳入了帕金森病进展标志物计划中的420例新发PD患者：180例仅患有PD（PD组），82例患有OD的PD患者（PD-OD组），94例患有pRBD的PD患者（PD-pRBD组），以及64例同时患有OD和pRBD的PD患者（PD-DH组）。参与者接受了运动和非运动评估、多巴胺转运体成像以及脑脊液（CSF）评估。数据采用广义估计方程和Cox比例风险分析进行分析。
PD-DH亚型在运动障碍协会统一PD评定量表（MDS-UPDRS）第二部分和第三部分中的得分更高且进展速度更快。此外，PD-DH组患者的非运动症状恶化更快，包括MDS-UPDRS第一部分得分、蒙特利尔认知评估、霍普金斯言语学习测试修订版、韦氏记忆量表第三版（WMS-III）字母数字序列得分、符号数字模态测试以及PD自主神经症状量表得分，所有P值均<0.002。此外，与PD组相比，PD-DH亚型发生轻度认知障碍的风险更高（风险比=1.756，95%置信区间[CI]=1.132-2.722；P=0.012），尾状核标准摄取值下降更快（β=-0.03，95%CI=-0.06至-0.008，P=0.012），CSFα-突触核蛋白水平下降更快（β=-77，95%CI=-149至-5，P=0.034）。
PD患者中同时存在pRBD和OD可能与运动指标以及认知和自主神经症状的更快进展相关，表明PD-DH是PD中一种更具侵袭性的亚型。
