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早期帕金森病中海马亚区萎缩与脑脊液生物标志物及认知的关系:一项横断面研究

Hippocampal subfield atrophy in relation to cerebrospinal fluid biomarkers and cognition in early Parkinson's disease: a cross-sectional study.

作者信息

Stav Ane Løvli, Johansen Krisztina Kunszt, Auning Eirik, Kalheim Lisa Flem, Selnes Per, Bjørnerud Atle, Hessen Erik, Aarsland Dag, Fladby Tormod

机构信息

Department of Neurology, Akershus University Hospital, Lørenskog, Norway.

Faculty Division Akershus University Hospital, University of Oslo, Oslo, Norway.

出版信息

NPJ Parkinsons Dis. 2016 Jan 14;2:15030. doi: 10.1038/npjparkd.2015.30. eCollection 2016.

Abstract

Cognition is often affected early in Parkinson's disease (PD). Lewy body and amyloid β (Aβ) pathology and cortical atrophy may be involved. The aim of this study was to examine whether medial temporal lobe structural changes may be linked to cerebrospinal fluid (CSF) biomarker levels and cognition in early PD. PD patients had smaller volumes of total hippocampus, presubiculum, subiculum, CA2-3, CA4-DG, and hippocampal tail compared with normal controls (NCs). In the PD group, lower CSF Aβ38 and 42 were significant predictors for thinner perirhinal cortex. Lower Aβ42 and smaller presubiculum and subiculum predicted poorer verbal learning and delayed verbal recall. Smaller total hippocampus, presubiculum and subiculum predicted poorer visuospatial copying. Lower Aβ38 and 40 and thinner perirhinal cortex predicted poorer delayed visual reproduction. In conclusion, smaller volumes of hippocampal subfields and subhippocampal cortex thickness linked to lower CSF Aβ levels may contribute to cognitive impairment in early PD. Thirty-three early PD patients (13 without, 5 with subjective, and 15 with mild cognitive impairment) and NC had 3 T magnetic resonance imaging (MRI) scans. The MRI scans were post processed for volumes of hippocampal subfields and entorhinal and perirhinal cortical thickness. Lumbar puncture for CSF biomarkers Aβ38, 40, 42, total tau, phosphorylated tau (Innogenetics), and total α-synuclein (Meso Scale Diagnostics) were performed. Multiple regression analyses were used for between-group comparisons of the MRI measurements in the NC and PD groups and for assessment of CSF biomarkers and neuropsychological tests in relation to morphometry in the PD group.

摘要

认知功能在帕金森病(PD)早期常受影响。路易小体和淀粉样β(Aβ)病理改变以及皮质萎缩可能与之相关。本研究旨在探讨内侧颞叶结构变化是否与早期PD患者的脑脊液(CSF)生物标志物水平及认知功能有关。与正常对照(NC)相比,PD患者的海马总体积、前扣带回、内嗅皮质、CA2 - 3、CA4 - 齿状回以及海马尾部体积较小。在PD组中,脑脊液Aβ38和42水平较低是梨状周围皮质变薄的显著预测因素。Aβ42水平较低以及前扣带回和内嗅皮质体积较小预示着言语学习能力较差和言语回忆延迟。海马总体积、前扣带回和内嗅皮质体积较小预示着视觉空间复制能力较差。Aβ38和40水平较低以及梨状周围皮质较薄预示着延迟视觉再现能力较差。总之,海马亚区体积减小以及海马旁皮质厚度与脑脊液Aβ水平降低相关,这可能导致早期PD患者出现认知障碍。33例早期PD患者(13例无认知障碍、5例有主观认知障碍、15例有轻度认知障碍)和正常对照接受了3T磁共振成像(MRI)扫描。对MRI扫描结果进行后处理,以测量海马亚区体积以及内嗅和梨状周围皮质厚度。进行腰椎穿刺以检测脑脊液生物标志物Aβ38、40、42、总tau蛋白、磷酸化tau蛋白(Innogenetics公司)以及总α - 突触核蛋白(Meso Scale Diagnostics公司)。采用多元回归分析对NC组和PD组的MRI测量结果进行组间比较,并评估PD组中脑脊液生物标志物与神经心理学测试结果之间的形态学关系。

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