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Meta-Analysis
. 2025 Jan 15;272(2):124.
doi: 10.1007/s00415-024-12871-7.

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

Ziyue Zhu  1 , Dennis Cordato  1   2 , Renfen Chen  3 , Ying Hua Xu  1   4 , Boaz Shulruf  1 , Daniel Kam Yin Chan  5   6
Affiliations
Meta-Analysis

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

Ziyue Zhu et al. J Neurol. .

Erratum in

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.

Keywords: Alpha-synuclein; Cognitive impairment; Parkinson’s disease; Plasma.

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Conflict of interest statement

Declarations. Conflict of interest: The authors did not receive support from any organisations for this submitted work. There are no competing interests to declare that are relevant to the content of this article.

References

    1. Emre M, Aarsland D, Brown R, Burn DJ, Duyckaerts C, Mizuno Y, Broe GA, Cummings J, Dickson DW, Gauthier S, Goldman J, Goetz C, Korczyn A, Lees A, Levy R, Litvan I, McKeith I, Olanow W, Poewe W, Quinn N, Sampaio C, Tolosa E, Dubois B (2007) Clinical diagnostic criteria for dementia associated with Parkinson’s disease. Mov Disord 22:1689–1707 - PubMed - DOI
    1. Aarsland D, Kurz MW (2010) The epidemiology of dementia associated with Parkinson’s disease. Brain Pathol 20:633–639 - PubMed - PMC - DOI
    1. Litvan I, Goldman JG, Tröster AI, Schmand BA, Weintraub D, Petersen RC, Mollenhauer B, Adler CH, Marder K, Williams-Gray CH, Aarsland D, Kulisevsky J, Rodriguez-Oroz MC, Burn DJ, Barker RA, Emre M (2012) Diagnostic criteria for mild cognitive impairment in Parkinson’s disease: movement disorder society task force guidelines. Mov Disord 27:349–356 - PubMed - PMC - DOI
    1. Baiano C, Barone P, Trojano L, Santangelo G (2020) Prevalence and clinical aspects of mild cognitive impairment in Parkinson’s disease: a meta-analysis. Mov Disord 35:45–54 - PubMed - DOI
    1. Aarsland D, Andersen K, Larsen JP, Lolk A, Nielsen H, Kragh-Sørensen P (2001) Risk of dementia in Parkinson’s disease: a community-based, prospective study. Neurology 56:730–736 - PubMed - DOI

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