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SCIENTIFIC LITERATURE · MED

Nigral Iron Deposition Influences Disease Severity by Modulating the Effect of Parkinson's Disease on Brain Networks.

J Parkinsons Dis · 2022-01-01

DOI: 10.3233/jpd-223372PMID: 36336939

Open accessResearch Support, Non-U.S. Gov't; research-article; Journal ArticleOriginal source ↗

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The text below is the source article’s original abstract under a verified reuse license. cc by

BackgroundIn Parkinson's disease (PD), excessive iron deposition in the substantia nigra may exacerbate α-synuclein aggregation, facilitating the degeneration of dopaminergic neurons and their neural projection.ObjectiveTo investigate the interaction effect between nigral iron deposition and PD status on brain networks.MethodsEighty-five PD patients and 140 normal controls (NC) were included. Network function and nigral iron were measured using multi-modality magnetic resonance imaging. According to the median of nigral magnetic susceptibility of NC (0.095 ppm), PD and NC were respectively divided into high and low nigral iron group. The main and interaction effects were investigated by mixed effect analysis.ResultsThe main effect of disease was observed in basal ganglia network (BGN) and visual network (VN). The interaction effect between nigral iron and PD status was observed in left inferior frontal gyrus and left insular lobe in BGN, as well as right middle occipital gyrus, right superior temporal gyrus, and bilateral cuneus in VN. Furthermore, multiple mediation analysis revealed that the functional connectivity of interaction effect clusters in BGN and medial VN partially mediated the relationship between nigral iron and Unified Parkinson's Disease Rating Scale II score.ConclusionOur study demonstrates an interaction of nigral iron deposition and PD status on brain networks, that is, nigral iron deposition is associated with the change of brain network configuration exclusively when in PD. We identified a potential causal mediation pathway for iron to affect disease severity that was mediated by both BGN dysfunction and VN hyperfunction in PD.

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