Brain functional network abnormalities in parkinson’s disease with mild cognitive impairment

Mild cognitive impairment in Parkinson’s disease (PD-M) is related to a high risk of dementia. This study explored the whole-brain functional networks in early-stage PD-M. Forty-one patients with PD classified as cognitively normal (PD-N, n = 17) and PD-M (n = 24) and 24 demographically matched healthy controls (HC) underwent clinical and neuropsychological evaluations and resting-state functional magnetic resonance imaging. The global, regional, and modular topological characteristics were assessed in the brain functional networks, and their relationships to cognitive scores were tested. At the global level, PD-M and PD-N exhibited higher characteristic path length and lower clustering coefficient, local and global efficiency relative to HC. At the regional level, PD-M and PD-N showed lower nodal centrality in sensorimotor regions relative to HC. At the modular level, PD-M showed lower intramodular connectivity in default mode and cerebellum modules, and lower intermodular connectivity between default mode and frontoparietal modules than PD-N, correlated with Montreal Cognitive Assessment scores. Early-stage PD patients showed weaker small-worldization of brain networks. Modular connectivity alterations were mainly observed in patients with PD-M. These findings highlight the shared and distinct brain functional network dysfunctions in PD-M and PD-N, and yield insight into the neurobiology of cognitive decline in PD.