Altered Whole-Brain Structural Covariance of the Hippocampal Subfields in Subcortical Vascular Mild Cognitive Impairment and Amnestic Mild Cognitive Impairment Patients

The hippocampus plays important roles in memory processing. However, the hippocampus is not a homogeneous structure, which consists of several subfields. The hippocampal subfields are differently affected by many neurodegenerative diseases, especially mild cognitive impairment (MCI). Amnestic mild cognitive impairment (aMCI) and subcortical vascular mild cognitive impairment (svMCI) are the two subtypes of MCI. aMCI is characterized by episodic memory loss, and svMCI is characterized by extensive white matter hyperintensities and multiple lacunar infarctions on magnetic resonance imaging. The primary cognitive impairment in svMCI is executive function, attention and semantic memory. Some variations or disconnections within specific largescale brain networks have been observed in aMCI and svMCI patients. The aim of this study was to investigate abnormalities in structural connections (SCNs) between hippocampal subfields and the whole cerebral cortex in aMCI and svMCI patients and whether these abnormalities are different between the two groups. Automated segmentation of hippocampal subfields was performed with FreeSurfer 5.3, and we selected five hippocampal subfields as the seeds of SCN analysis: CA1, CA2/3, CA4/DG, subiculum, and presubiculum. SCNs were constructed based on these hippocampal subfield seeds for each group. Significant correlations between hippocampal subfields, fusiform gyrus, and entorhinal cortex in gray matter volume were found in each group. We also compared the differences in the strength of structural covariance between any two groups. In the aMCI group, compared to the NC group, we observed an increased association between the left CA1/CA4/DG/subiculum and the left temporal pole. Additionally, the hippocampal subfields (bilateral CA1, left CA2/3) significantly covaried with the orbitofrontal cortex in the svMCI group compared to the NC group. In the aMCI group compared to the svMCI group, we observed decreased association between hippocampal subfields and the right fusiform gyrus, while we also observed an increased association between the bilateral subiculum/presubiculum and bilateral entorhinal cortex. These findings provide new evidence that there is altered whole-brain structural covariance of the hippocampal subfields in svMCI and aMCI patients and provide insights to the pathological mechanisms of different MCI subtypes.