title: Exploring Patterns of Alteration in Alzheimer's Disease Brain Networks: A Combined Structural and Functional Connectomics Analysis.
abstract: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a severe derangement of cognitive functions, primarily memory, in elderly subjects. As far as the functional impairment is concerned, growing evidence supports the "disconnection syndrome" hypothesis. Recent investigations using fMRI have revealed a generalized alteration of resting state networks (RSNs) in patients affected by AD and mild cognitive impairment (MCI). However, it was unclear whether the changes in functional connectivity were accompanied by corresponding structural network changes. In this work, we have developed a novel structural/functional connectomic approach: resting state fMRI was used to identify the functional cortical network nodes and diffusion MRI to reconstruct the fiber tracts to give a weight to internodal subcortical connections. Then, local and global efficiency were determined for different networks, exploring specific alterations of integration and segregation patterns in AD and MCI patients compared to healthy controls (HC). In the default mode network (DMN), that was the most affected, axonal loss, and reduced axonal integrity appeared to compromise both local and global efficiency along posterior-anterior connections. In the basal ganglia network (BGN), disruption of white matter integrity implied that main alterations occurred in local microstructure. In the anterior insular network (AIN), neuronal loss probably subtended a compromised communication with the insular cortex. Cognitive performance, evaluated by neuropsychological examinations, revealed a dependency on integration and segregation of brain networks. These findings are indicative of the fact that cognitive deficits in AD could be associated not only with cortical alterations (revealed by fMRI) but also with subcortical alterations (revealed by diffusion MRI) that extend beyond the areas primarily damaged by neurodegeneration, toward the support of an emerging concept of AD as a "disconnection syndrome." Since only AD but not MCI patients were characterized by a significant decrease in structural connectivity, integrated structural/functional connectomics could provide a useful tool for assessing disease progression from MCI to AD.
authors.affiliation: Department of Physics, University of PaviaPavia, Italy; Brain Connectivity Center, C. Mondino National Neurological InstitutePavia, Italy.
authors.forename: Fulvia
authors.initials: F
authors.lastname: Palesi
authors.affiliation: Brain Connectivity Center, C. Mondino National Neurological InstitutePavia, Italy; Department of Electrical, Computer and Biomedical Engineering, University of PaviaPavia, Italy.
authors.forename: Gloria
authors.initials: G
authors.lastname: Castellazzi
authors.affiliation: Brain Connectivity Center, C. Mondino National Neurological InstitutePavia, Italy; Department of Brain and Behavioural Sciences, University of PaviaPavia, Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: Casiraghi
authors.affiliation: Neuroradiology Unit, C. Mondino National Neurological Institute Pavia, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Sinforiani
authors.affiliation: Neuroradiology Unit, C. Mondino National Neurological InstitutePavia, Italy; Brain MRI 3T Mondino Research Center, C. Mondino National Neurological InstitutePavia, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Vitali
authors.affiliation: Department of Brain and Behavioural Sciences, University of PaviaPavia, Italy; Brain MRI 3T Mondino Research Center, C. Mondino National Neurological InstitutePavia, Italy; NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of NeurologyLondon, UK.
authors.forename: Claudia A M
authors.initials: CA
authors.lastname: Gandini Wheeler-Kingshott
authors.affiliation: Brain Connectivity Center, C. Mondino National Neurological InstitutePavia, Italy; Department of Brain and Behavioural Sciences, University of PaviaPavia, Italy.
authors.forename: Egidio
authors.initials: E
authors.lastname: D'Angelo
keywords: AD; connectomics; disconnection syndrome; probabilistic tractography; resting state networks