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特定认知领域的衰退与帕金森病患者的血浆和神经影像学标志物相关。

A task-specific cognitive domain decline is correlated with plasma and neuroimaging markers in patients with Parkinson's disease.

机构信息

Department of Neurology, College of Medicine, National Taiwan University Hospital, National Taiwan University, Taipei, 100, Taiwan.

Department of Neurology, National Taiwan University Hospital Hsinchu Branch, Hsin-chu, Taiwan.

出版信息

J Neurol. 2022 Dec;269(12):6530-6543. doi: 10.1007/s00415-022-11301-w. Epub 2022 Aug 14.

Abstract

BACKGROUND

Cognitive impairment is a disabling non-motor symptom of Parkinson's disease (PD). It remains uncertain whether declines in specific cognitive domains relate to imaging or plasma biomarkers across the disease continuum.

OBJECTIVE

We investigated whether neuroimaging and plasma biomarkers correlate with individual task-specific cognitive domain declines evidenced by computerized neuropsychological tests in PD patients.

METHODS

A total of 107 participants, including 87 PD patients (30 with normal cognition [PD-NC], 30 with mild cognitive impairment [PD-MCI], 27 with dementia [PDD]), and 20 healthy controls, were recruited. All received the Cambridge Neuropsychological Test Automatic Battery (CANTAB) test, brain MRI, and assays of plasma biomarkers, including α-synuclein, tau, Aβ42, and Aβ40.

RESULTS

PD patients had generally poorer cognitive performance than controls. Patients with PD-MCI and PDD had worse performance in visual, verbal, and working memory and executive function than those with PD-NC. After adjusting for covariates, PDD patients had global cortical thinning, especially in the temporal and parietal lobes, and higher plasma α-synuclein levels and tau:Aβ42 ratios than PD-NC group. Plasma α-synuclein level was associated with frontal lobe-mediated tasks, while the tau:Aβ42 ratio was associated with posterior cortical-mediated tasks. Facial emotion recognition tasks and visual pattern recognition associated with frontotemporal cortical thinning. The accuracy of predicting PDD using age alone (area under the curve [AUC] 0.756) increased by incorporating plasma biomarkers (AUC = 0.851, p = 0.025).

CONCLUSIONS

Cognitive decline in PD patients has a task-specific correlation with neuroimaging and plasma biomarkers, which may implicate the underlying neuropathological process of PDD.

摘要

背景

认知障碍是帕金森病(PD)的一种致残性非运动症状。目前尚不确定疾病连续体中特定认知领域的下降是否与影像学或血浆生物标志物相关。

目的

我们研究了神经影像学和血浆生物标志物是否与 PD 患者的计算机化神经心理学测试所证实的特定认知领域的个体任务下降相关。

方法

共招募了 107 名参与者,包括 87 名 PD 患者(30 名认知正常[PD-NC],30 名轻度认知障碍[PD-MCI],27 名痴呆[PDD])和 20 名健康对照者。所有参与者均接受了剑桥神经心理学测试自动电池(CANTAB)测试、脑部 MRI 和血浆生物标志物(包括α-突触核蛋白、tau、Aβ42 和 Aβ40)检测。

结果

PD 患者的认知表现普遍较差。与 PD-NC 相比,PD-MCI 和 PDD 患者的视觉、言语和工作记忆以及执行功能更差。在调整协变量后,PDD 患者的全脑皮质变薄,尤其是颞叶和顶叶,且血浆α-突触核蛋白水平和 tau:Aβ42 比值较高。血浆α-突触核蛋白水平与额叶介导的任务相关,而 tau:Aβ42 比值与皮质后区介导的任务相关。面部情绪识别任务和视觉模式识别与额颞皮质变薄相关。仅使用年龄预测 PDD 的准确率(曲线下面积[AUC]为 0.756),通过纳入血浆生物标志物(AUC 为 0.851,p 为 0.025)而提高。

结论

PD 患者的认知下降与神经影像学和血浆生物标志物具有特定任务相关性,这可能暗示了 PDD 的潜在神经病理学过程。

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