Alzheimer’s disease is associated with increased modularity and assortativity: Evidence from structural and metabolic connectivity

Abstract

AbstractBackgroundAlzheimer’s disease (AD) is a progressive disorder associated with cognitive dysfunction that alters brain connectivity and assessing these altered connectivity patterns has become a topic of increasing interest. In this study, we examine the structural and metabolic connectivity using cortical thickness and [18F] Flouro deoxyglucose (FDG)‐positron emission tomography (PET) to identify the network modification in patient with AD when compared to mild cognitive impairment (MCI). To examine our hypothesis; we quantified a relatively newer graph theory measures including assortativity and modularity. We aimed to unravel the multimodal network alterations using simultaneous MRI‐PET acquisitions.MethodsPatients who underwent simultaneous FDG‐PET and MRI study on a 3T MRI were recruited for this exploratory study. After appropriate pre‐processing of structural‐MRI and PET‐metabolic data, graph measures were obtained using the BRAPH toolbox, and subsequently; global and nodal network measures were used to derive group‐level differences (corrected p<0.05). Regions that revealed significant differences were correlated with the cognitive scores (ACE‐III).Results83 demographically matched patients [MCI (n = 27), and AD (n = 56)] were analysed. There were no significant differences between the groups in the mean age (MCI 63.52 ±9.19 years and AD 63.73 ±9.60 years), gender (M: F) MCI 20:7 and AD 26:30, or the mean duration of disease (MCI 2.23±1.92 and AD 2.95 years) other than ACE scores (MCI‐87.30±5.53 and AD 46.02 ±20.61, p value <0.001) and the CDR (MCI‐very mild and AD‐Moderate and Severe). Patients with AD revealed significantly increased assortativity at the global level in both structural and metabolic connectivity analysis. In addition, metabolic connectivity revealed increased modularity and decreased participation coefficient in patients with AD. Cortical thickness and SUV abnormalities in several regions in bilateral parietotemporal lobes were proportional with the cognitive scores (ACE‐III).ConclusionProbable erroneous and homophilic network segregation paralleling the aging associated loss of whole brain integration was found proportional to the memory scores. Further studies in larger cohorts are required to ascertain the clinical relevance of these findings as an imaging biomarker.