Patterns of a structural covariance network associated with Mild Behavioural Impairment in biologically defined Alzheimer’s Disease

Background: The frequent presentation of Alzheimer’s disease (AD) with neuropsychiatric symptoms (NPS) in the context of normal or minimally-impaired cognitive function led to the concept of Mild Behavioral Impairment (MBI). While MBI's impact on subsequent cognitive decline is recognized, its association with brain network changes in biologically-defined AD remains unexplored. Methods: We investigated correlations between structural covariance networks and MBI-C checklist sub-scores in 33 biologically-defined AD patients (ranging from Mild Cognitive Impairment to early dementia). Network properties were assessed through graph theory analysis. The subjects were all characterized as amyloid-positive, whether assessed through cerebrospinal fluid (CSF) analysis or amyloid positron emission tomography (PET) scans. Results: Affective dysregulation correlated with decreased segregation and integration in the right inferior frontal gyrus (IFG). Impulse dyscontrol and social inappropriateness correlated positively with centrality and efficiency in the right posterior cingulum cortex (PCC). Global network properties showed a preserved small-world organization. Conclusions: This study reveals associations between MBI subdomains and structural brain network alterations in biologically-confirmed AD. Our data suggest that the IFG's involvement is crucial for mood dysregulation in AD, while PCC could be involved in compensatory mechanisms in respect to social cognition and impulse control. In conclusion, our findings provide further evidence that network changes in specific brain regions may be related to NPS across the AD spectrum and underscore the significance of biomarker-based neuroimaging for precise differential diagnosis of MBI.