Functional Connectome Organization is Altered in PD Patients with Mild Cognitive Impairment (P4.108)

Background: Investigation of the brain wiring architecture is a powerful approach in the examination of the pathogenic mechanisms of neurodegenerative disease. Objective: To investigate the functional brain connectome organization in patients with Parkinson’s disease (PD) with mild cognitive impairment (MCI). Methods: 54 PD-MCI patients, 54 demographically matched PD patients with no cognitive impairment (PD-ncog), and 41 healthy controls underwent resting state functional MRI (fMRI). Graph theory analysis was used to measure the global topological properties of functional brain networks in patients and controls. Differences in regional functional networks among groups were investigated using Network-based statistic (NBS). Results: PD-ncog patients did not show altered global graph theory measures and regional functional connections relative to controls. The analysis of the global graph theoretical measures showed that PD-MCI had significantly lower mean network degree, connections density, and global efficiency as well as higher path length when compared to controls and PD-ncog. No significant differences in clustering coefficient and assortativity were found. NBS analysis revealed that, relative to healthy subjects, PD-MCI patients showed a large network of reduced functional connectivity that included precentral, superior and inferior frontal (pars triangularis) gyri, anterior and posterior cingulate cortices, and supramarginal gyri and insula bilaterally. Left putamen and superior parietal gyrus, as well as right inferior frontal (pars opercularis), postcentral and paracentral gyri were also included in the network. Conclusions: The topological properties of brain networks are altered in PD patients with cognitive deficits, suggesting a loss of efficiency of long-distance functional connections. The pattern of these alterations and their anatomical distribution suggest that they might reflect the neuropathological substrate underlying PD-related cognitive impairment. Assessing functional brain network abnormalities in PD patients with cognitive impairment could improve our understanding of the relationship between PD pathology and cognitive deficits. Supported by: Italian Ministry of Health (Grant #GR091577482).