Aberrant hippocampal subregional network associated with episodic memory decline in amnestic mild cognitive impairment.

Background: Amnestic mild cognitive impairment (aMCI) is characterized by marked episodic memory decline. The hippocampus is essential for episodic memory, and integration of information within its subregions is central to this process. This study examined how alterations in hippocampal subregional network relate to episodic memory impairment in aMCI.

Methods: Participants with aMCI (n = 32) were recruited between March 2021 and May 2022, with cognitively normal controls (n = 32) matched for age, sex, and years of education. Episodic memory was evaluated using the Logical Memory subtest of the Wechsler Memory Scale-Revised. Resting-state functional MRI data were acquired. Hippocampal subregional networks were constructed to characterize functional connectivity and topological alterations in aMCI. Pearson correlation analyses were used to assess the relationships between network metrics and episodic memory function.

Results: We found impaired integration of the hippocampal subregion network in aMCI, as reflected by increased path length and decreased global efficiency (p < 0.05). Longer path length correlated with lower Logical Memory scores. Functional connectivity decreased between the bilateral parasubiculum and the left granule and molecular layer of the dentate gyrus and between the right parasubiculum and left CA1 (connection-level threshold p < 0.001, network-level threshold pFDR < 0.05). Nodal analyses revealed reduced degree centrality and nodal efficiency in the bilateral parasubiculum and presubiculum (pFDR < 0.05), both positively associated with episodic memory in aMCI (pFDR < 0.05).

Conclusions: These findings suggest that episodic memory impairment in aMCI is linked to altered hippocampal subregional integration, with the parasubiculum and presubiculum as potential key regions.