Abstract
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. OBJECTIVE: To investigate the correlation of structural covariance networks with MBI-C checklist sub-scores in biologically-defined AD patients. METHODS: We analyzed 33 biologically-defined AD patients, ranging from mild cognitive impairment to early dementia, all characterized as amyloid-positive through cerebrospinal fluid analysis or amyloid positron emission tomography scans. Regional network properties were assessed through graph theory. 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 cingulate 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. The IFG's involvement is crucial for mood dysregulation, while the PCC could be involved in compensatory mechanisms for social cognition and impulse control. These findings underscore the significance of biomarker-based neuroimaging for the characterization of NPS across the AD spectrum.