Characteristics of the default mode functional connectivity in normal ageing and Alzheimer's disease using resting state fMRI with a combined approach of entropy-based and graph theoretical measurements

Cognitive decline in normal ageing and Alzheimer's disease (AD) emerges from functional disruption in the coordination of large-scale brain systems sustaining cognition. Integrity of these systems can be examined by correlation methods based on analysis of resting state functional magnetic resonance imaging (fMRI).Here we investigate functional connectivity within the default mode network (DMN) in normal ageing and AD using resting state fMRI. Images from young and elderly controls, and patients with AD were processed using spatial independent component analysis to identify the DMN. Functional connectivity was quantified using integration and indices derived from graph theory. Four DMN sub-systems were identified: Frontal (medial and superior), parietal (precuneus-posterior cingulate, lateral parietal), temporal (medial temporal), and hippocampal (bilateral). There was a decrease in antero-posterior interactions (lower global efficiency), but increased interactions within the frontal and parietal sub-systems (higher local clustering) in elderly compared to young controls. This decreased antero-posterior integration was more pronounced in AD patients compared to elderly controls, particularly in the precuneus-posterior cingulate region. Conjoint knowledge of integration measures and graph indices in the same data helps in the interpretation of functional connectivity results, as comprehension of one measure improves with understanding of the other. The approach allows for complete characterisation of connectivity changes and could be applied to other resting state networks and different pathologies.