The mediating role of hippocampal networks on stress regulation in amnestic mild cognitive impairment

Objectives: To examine the role of the hippocampus in stress regulation in older adults with amnestic mild cognitive impairment (aMCI). Methods: This study combined resting-state functional MRI, structural MRI, self-reported chronic stress exposure, and an electrocardiography-based acute stress protocol to compare aMCI group (n = 17) to their cognitively healthy counterparts (HC, n = 22). Results: For the entire sample, there was a positive correlation between chronic stress exposure and acute stress regulation. The aMCI group showed significantly smaller volumes in the right hippocampus than HC. The two groups did not differ in chronic stress exposure or acute stress regulation. In the HC group, the left hippocampal connectivity with inferior parietal lobe was significantly correlated with both the chronic stress and acute stress. In the aMCI group, the left hippocampal connectivity with both the right insula and the left precentral gyrus was significantly correlated to chronic stress exposure and acute stress regulation. Additionally, the left hippocampal connectivity with right insula significantly mediated the relationship between chronic stress exposure and acute stress regulation in aMCI group. Conclusions: Extra hippocampal networks may be recruited as compensation to attend the maintenance of relatively normal stress regulation in aMCI by alleviating the detrimental effects of chronic stress exposure on acute stress regulation.