The Effect Of Age Of Onset On The Brain Functional Connectivity In Alzheimer’s Disease: A Graph Analysis Study (P6.312)

OBJECTIVE: To examine the relation between the topological organization of functional brain networks and the age of onset in patients with Alzheimer’s disease (AD) using a network-based approach. BACKGROUND: Brain connectomics opened new horizons to the understanding of brain organization and could add significant advances to the understanding of AD at different age of onset. DESIGN/METHODS: Graph theoretical analysis was applied to resting state functional MRI data from 36 late onset AD (LOAD) patients (age:75± 5, CDR-SB:6±2), 23 early onset (EOAD) patients (age:60±5, CDR-SB 5±2) and two groups of old (N:16, age:73±4) and young (N:22, age:59±3) healthy individuals. Functional connectivity between 90 cortical and subcortical brain regions was estimated using bivariate correlation analysis and thresholded to construct a set of undirected graphs. Measures of global and local network organization were obtained. RESULTS: Small-worldness was verified in controls and patients. Globally, the functional brain networks of LOAD patients were characterized by a significantly lower local and global efficiency, lower clustering coefficient and higher assortativity compared with age-matched controls. In contrast, functional brain networks of EOAD patients were characterized by a significantly higher hierarchy and lower assortativity compared with age-matched controls. Locally, lower nodal degree and local efficiency, and higher betweeness centrality were observed in both AD groups compared to the age-matched controls. However, while LOAD showed local alterations (in terms of decreased nodal degree and increased betweeness centrality) in the medial temporal, parietal and occipital lobes, EOAD patients showed a widespread pattern of damage involving also the frontal regions. CONCLUSIONS: Graph analysis showed that global functional network organization was abnormal in AD patients. Compared to LOAD, the EOAD patients showed a widespread pattern of local network alterations involving also the frontal regions. The topological differences between patient groups may represent the effect of age of onset on functional connections. Study Supported by: Italian Ministry of Health (Grant #GR-2010-2303035).