Stage-dependent differential impact of network communication on cognitive function across the continuum of cognitive decline in Parkinson's disease

Our objective was to explore the patterns of resting-state network (RSN) connectivity alterations and investigate how the influences of individual-level network connections on cognition varied across clinical stages without assuming a constant relationship. 108 PD patients with continuum of cognitive decline (PD-NC = 46, PD-MCI = 43, PDD = 19) and 34 healthy controls (HCs) underwent resting-state functional MRI and neuropsychological tests. Independent component analysis (ICA) and graph theory analyses (GTA) were employed to explore RSN connection changes. Additionally, stage-dependent differential impact of network communication on cognitive performance were examined using sparse varying coefficient modeling. Compared to HCs, the dorsal attention network (DAN) and dorsal sensorimotor network (dSMN) were central networks with decreased connections in PD-NC and PD-MCI stage, while the lateral visual network (LVN) emerged as a central network in patients with dementia. Additionally, connectivity of the cerebellum network (CBN) increased in the PD-NC and PD-MCI stages. GTA demonstrated decreased nodal metrics for DAN and dSMN, coupled with an increase for CBN. Moreover, the degree centrality (DC) values of DAN and dSMN exhibited a stage-dependent differential impact on cognitive performance across the continuum of cognitive decline. Our findings suggest that across the progression of cognitive impairment, the LVN gradually transitions into a core node with reduced connectivity, while the enhancement of connections in CBN diminishes. Furthermore, the non-linear relationship between the DC values of RSNs and cognitive decline indicates the potential for tailored interventions targeting specific stages.