Large-scale reorganization of cortical hierarchy, dynamics, and information processing in subjective cognitive decline

Subjective cognitive decline (SCD) represents a clinically important but mechanistically elusive stage along the Alzheimers disease (AD) continuum, characterized by persistent cognitive complaints despite preserved performance on standard neuropsychological tests. Individuals with SCD show an increased risk of progression to mild cognitive impairment and dementia; however, the large-scale functional architecture underlying subjective cognitive symptoms remains poorly defined. In this study, we investigated cortical functional hierarchy, hierarchical brain dynamics, and information-processing architecture in individuals with SCD using resting-state functional magnetic resonance imaging. We first characterized the principal functional gradient spanning sensory to transmodal association cortices and quantified its global dispersion. We then examined the directionality of hierarchical brain dynamics to assess alterations in bottom-up and top-down information flow. Finally, we applied an integrated information decomposition framework to quantify synergistic and redundant interactions across large-scale brain networks, and related these measures to clinical characteristics and molecular-cellular substrates. Compared with healthy controls, individuals with SCD exhibited significant regional alterations in functional gradient organization, predominantly affecting association cortices, alongside increased gradient dispersion, indicating a less compact and more heterogeneous cortical hierarchy. Hierarchical dynamics were shifted toward enhanced bottom-up information flow, suggesting increased reliance on sensory-driven processing. Integrated information decomposition revealed widespread reductions in both synergistic and redundant interactions, reflecting impaired integrative capacity and reduced informational robustness of distributed brain systems. These functional alterations were associated with symptom duration and depressive burden, and showed spatial correspondence with neurotransmitter receptor distributions and cell-type-specific gene expression profiles. Together, these findings demonstrate that SCD is characterized by coordinated disruptions in cortical hierarchy, hierarchical dynamics, and information-processing organization. Our results provide a systems-level account of early functional brain reorganization in SCD and support its conceptualization as an early functional manifestation of AD-related vulnerability, prior to objective cognitive impairment.