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. 2025 Jan;31(1):e70198.
doi: 10.1111/cns.70198.

Olfactory Network Disruptions as Mediators of Cognitive Impairment in De Novo Parkinson's Disease

Yi Xing  1 , Hao Zhou  1 , Shuoying Chen  1 , Yajie Wang  2 , Jingru Ren  1 , Yiting Cao  1 , Jingzhe Li  1 , Weiguo Liu  1
Affiliations

Olfactory Network Disruptions as Mediators of Cognitive Impairment in De Novo Parkinson's Disease

Yi Xing et al. CNS Neurosci Ther. 2025 Jan.

Abstract

Objectives: Parkinson's disease (PD) is characterized by olfactory dysfunction (OD) and cognitive deficits at its early stages, yet the link between OD and cognitive deficits is also not well-understood. This study aims to examine the changes in the olfactory network associated with OD and their relationship with cognitive function in de novo PD patients.

Methods: A total of 116 drug-naïve PD patients and 51 healthy controls (HCs) were recruited for this study. Graph theoretical approaches were employed to reveal the abnormalities of topological characteristics in the olfactory network. Network-based statistics (NBS) analysis was employed to identify the abnormal subnetworks within the olfactory network. Moreover, partial correlation analysis and mediation analysis were performed to examine the relationship between the abnormal network metrics, olfactory function, and cognitive function.

Results: Graph theoretical approaches revealed reduced betweenness centrality of the left insula in PD patients with OD. NBS analysis identified a disrupted subnetwork with decreased functional connectivity, primarily involving limbic regions. The average functional connectivity of this subnetwork partially mediated the relationship between olfactory and cognitive performance. Higher-granularity network analysis further highlighted the insula's key role and revealed reduced efficiency of information integration within the olfactory network.

Conclusions: OD was associated with specific changes in the functional olfactory network, which, in turn, affects cognitive function. These findings underscore the importance of assessing and addressing OD. Understanding the neural correlates of OD could provide novel insights into the management and comprehension of cognitive impairment in PD.

Keywords: NBS; Parkinson's disease; cognitive impairment; olfactory dysfunction; olfactory network.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
(A) Unilateral 17 nodes in olfactory network: Olfactory cortex, Anterior cingulate cortex pregenual (ACCpre), Anterior cingulate cortex subgenual (ACCsub), Anterior cingulate cortex supracollasal (ACCsup), Amygdala, Caudate nucleus, Hippocampus, Nucleus Accumbens (NAcc), nucleus Pallidum, ParaHippocampal gyrus, Putamen, Anterior orbital gyrus (OFCant), Lateral orbital gyrus (OFClat), Medial orbital gyrus (OFCmed), Posterior orbital gyrus (OFCpost), Insula and Thalamus. (B) The correlation between the MoCA and SST scores among PD patients. (C) The intergroup differences in aBc of the left insula. *p < 0.05, **p < 0.01, **p < 0.001.
FIGURE 2
FIGURE 2
(A) The subnetwork exhibiting decreased functional connectivity in the OD group compared to the NOD group in Analysis Part I. (B) The correlation between the aBC of the left insula and the SST score. (C–E) The correlation between the average FC of the identified subnetwork and the SST, MoCA scores, and z‐score of the memory domain.
FIGURE 3
FIGURE 3
Mediation models with the average FC of the identified subnetwork as a mediator between SST and MoCA scores. *p < 0.05, **p < 0.01, **p < 0.001.
See this image and copyright information in PMC

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