Distinct Atrophy Pattern of Hippocampal Subfields in Patients with Progressive and Stable Mild Cognitive Impairment: A Longitudinal MRI Study

Abstract

Background: Predicting the prognosis of mild cognitive impairment (MCI) has outstanding clinical value, and the hippocampal volume is a reliable imaging biomarker of AD diagnosis.

Objective: We aimed to longitudinally assess hippocampal sub-regional difference (volume and asymmetry) among progressive MCI (pMCI), stable MCI (sMCI) patients, and normal elderly.

Methods: We identified 29 pMCI, 52 sMCI, and 102 normal controls (NC) from the ADNI database. All participants underwent neuropsychological assessment and 3T MRI scans three times. The time interval between consecutive MRI sessions was about 1 year. Volumes of hippocampal subfield were measured by Freesurfer. Based on the analysis of variance, repeated measures analyses, and receiver operating characteristic curves, we compared cross-sectional and longitudinal alteration sub-regional volume and asymmetry index.

Results: Compared to NC, both MCI groups showed significant atrophy in all subfields. At baseline, pMCI have a smaller volume than sMCI in the bilateral subiculum, molecular layer (ML), the molecular and granule cell layers of the dentate gyrus, cornu ammonis 4, and right tail. Furthermore, repeated measures analyses revealed that pMCI patients showed a faster volume loss than sMCI in bilateral subiculum and ML. After controlling for age, gender, and education, most results remained unchanged. However, none of the hippocampal sub-regional volumes performed better than the whole hippocampus in ROC analyses, and no asymmetric difference between pMCI and sMCI was found.

Conclusion: The faster volume loss in subiculum and ML suggest a higher risk of disease progression in MCI patients. The hippocampal asymmetry may have smaller value in predicting the MCI prognosis.

Keywords: Alzheimer’s disease; hippocampal subfields; mild cognitive impairment; molecular layer; subiculum.