Plasma alpha-synuclein predicts cognitive impairment in Parkinson's disease: a systematic review and meta-analysis.

IF 4.8 2区 医学 Q1 CLINICAL NEUROLOGY Journal of Neurology Pub Date : 2025-01-15 DOI:10.1007/s00415-024-12871-7
Ziyue Zhu, Dennis Cordato, Renfen Chen, Ying Hua Xu, Boaz Shulruf, Daniel Kam Yin Chan
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Abstract

Background: Alpha-synuclein (ɑ-syn) plays a key role in Parkinson's disease (PD) pathogenesis, but existing studies have found mixed results regarding the associations between plasma ɑ-syn and the development of cognitive impairment. We aim to clarify the potentially important relationship between ɑ-syn level in plasma and development of cognitive impairment in PD through systematic review and meta-analysis.

Methods: A systematic search was conducted in the PubMed, Embase and Web of Science databases for studies reporting plasma ɑ-syn concentrations and cognitive impairment in PD. Effect directions were plotted to investigate methodological factors, and a meta-analysis was performed comparing PD patients with dementia (PDD) to PD patients with normal cognition (PDNC).

Results: Twenty-five studies were identified for the systematic review, involving 1,888 PD patients. Studies using the clinical diagnostic Movement Disorder Society (MDS) criteria for PD with mild cognitive impairment and PDD found consistently positive associations with plasma ɑ-syn level. This was further supported by a meta-analysis which found a significant standardised mean difference (g = 1.770, 95% CI: 0.749-2.790, p < 0.001) between PDD and PDNC patients in 10 studies. Furthermore, studies using emerging immunomagnetic reduction or single-molecule array techniques to quantify ɑ-syn reported strong positive associations. In contrast, studies using enzyme-linked immunoassay and cognitive screening tests alone found mixed results.

Conclusion: There is an overall positive effect between plasma ɑ-syn levels and cognitive impairment in PD. As methodological factors can significantly affect associations, future studies should carefully select ɑ-syn immunoassays and utilise the MDS diagnostic criteria for cognitive impairment in PD.

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血浆α -突触核蛋白预测帕金森病的认知障碍:一项系统回顾和荟萃分析
背景:α -突触核蛋白在帕金森病(PD)发病机制中起着关键作用,但现有研究发现血浆中α -突触蛋白与认知功能障碍之间的关系好坏参半。我们旨在通过系统综述和荟萃分析来阐明血浆中α -syn水平与PD患者认知功能障碍发展之间的潜在重要关系。方法:系统检索PubMed、Embase和Web of Science数据库中有关PD患者血浆中α -syn浓度与认知功能障碍的研究。绘制影响方向以调查方法学因素,并对PD合并痴呆(PDD)患者与PD认知正常(PDNC)患者进行meta分析。结果:25项研究被纳入系统评价,涉及1888名PD患者。使用临床诊断运动障碍协会(MDS)标准对PD合并轻度认知障碍和PDD的研究发现血浆中* * -syn水平始终呈正相关。一项荟萃分析进一步支持了这一观点,发现标准化平均差异显著(g = 1.770, 95% CI: 0.749-2.790, p)。结论:血浆中α -syn水平与PD患者认知功能障碍之间存在总体正相关。由于方法学因素可以显著影响关联,未来的研究应谨慎选择免疫分析方法,并利用MDS诊断PD患者认知障碍的标准。
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来源期刊
Journal of Neurology
Journal of Neurology 医学-临床神经学
CiteScore
10.00
自引率
5.00%
发文量
558
审稿时长
1 months
期刊介绍: The Journal of Neurology is an international peer-reviewed journal which provides a source for publishing original communications and reviews on clinical neurology covering the whole field. In addition, Letters to the Editors serve as a forum for clinical cases and the exchange of ideas which highlight important new findings. A section on Neurological progress serves to summarise the major findings in certain fields of neurology. Commentaries on new developments in clinical neuroscience, which may be commissioned or submitted, are published as editorials. Every neurologist interested in the current diagnosis and treatment of neurological disorders needs access to the information contained in this valuable journal.
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