Hippocampal-cortical structural networks in the progression of cognitive impairment: A source-based morphometry analysis in individuals with subjective cognitive decline, mild cognitive impairment and Alzheimer's disease

Neural plasticity and memory mechanisms progressively change during pathological aging. This study aimed to identify patterns of structural covariance across Alzheimer’s disease (AD) stages and their relationship with episodic memory performance. Fifty-nine AD patients, 59 patients with amnestic Mild Cognitive Impairment (a-MCI), 46 individuals with Subjective Cognitive Decline (SCD), and 49 Healthy Controls (HC) underwent neuropsychological assessment, including verbal episodic memory tests (15-Word List and Short Story) and 3 T Magnetic Resonance Imaging (MRI). T1-weighted images were processed using the Source-Based Morphometry (SBM) pipeline to extract structural covariance networks. Group differences were assessed using ANCOVA, and correlations with memory performance were examined using Pearson’s coefficients. Three hippocampal–cortical networks were identified: the hippocampal–diencephalic network (HDN), hippocampal–anterior cingulate–occipital network (HACON), and mesiotemporal–orbitofrontal network (MTON). AD patients showed marked reductions in grey matter connectivity across all networks, while a-MCI patients exhibited intermediate values, particularly in HDN and MTON. Network-memory correlations showed distinct patterns across groups: in HC, HDN and HACON correlated with recall and recognition, whereas MTON connectivity correlated with memory performance in SCD, a-MCI, and AD. These findings indicate a stage-dependent disruption of hippocampal–cortical networks and suggest that MTON integrity supports long-term memory, with progressive disconnection contributing to severe impairment in AD.