Local Brain Connectome Parameters Across the Spectrum of Clinical Cognitive Decline

Abstract

Neurological disorders such as Alzheimer’s disease, Parkinson’s disease, and autism disrupt the brain’s structural and functional organization, particularly in specific regions, and ultimately lead to cognitive impairments. In Alzheimer’s disease-related dementia, neuronal degeneration impairs structural connectivity between brain regions, which in turn leads to functional breakdowns. This phenomenon, referred to as disconnection syndrome, manifests as connectivity breakdowns in a􀀀ected regions, with these localized changes indirectly influencing the entire brain network. As the disease progresses, patterns consistent with compensatory-type reorganization have been described in the literature, accompanied by structural and functional changes that have been hypothesized to transiently mitigate cognitive decline during early stages. This study examines the structural and functional reorganization of the brain across the clinical spectrum of Alzheimer’s disease by analyzing local nodal changes using measures such as degree, strength, clustering coe cient, and betweenness centrality. Our findings show that early-stage nodal patterns are consistent with this hypothesized reorganization, whereas later-stage changes are dominated by progressive structural decline alongside persistent functional reorganization. Because the present study is cross-sectional and group-level, the compensatory interpretation should be regarded as a working hypothesis rather than a confirmed mechanism, and these exploratory patterns require validation in independent and longitudinal cohorts before clinical translation.