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.