Hippocampal subfield volumes in mild cognitive impairment and alzheimer's disease: a systematic review and meta-analysis

The hippocampus is a complex structure that consists of several subfields with distinct and specialized functions. Although numerous studies have been performed to explore hippocampal atrophy at the sub-regional level in mild cognitive impairment (MCI) and Alzheimer's disease (AD), the results have been inconsistent especially for whether and which subfields can be served as the most potential biomarkers in MCI and AD. Herein, we used a meta-analytic approach to synthesize the extant literatures on hippocampal subfields in MCI and AD through PubMed, Web of Science, and Embase (PROSPERO CRD42021257586). As a result, a total of twenty studies using Freesurfer 5 and Freesurfer 6 were included in this investigation. These studies revealed that at the sub-regional level, hippocampal subfield volume reductions in MCI and AD were not restricted to specific subfields, and subiculum and presubiculum had the largest z-scores across most comparisons. However, none of the subfield performed much better in discriminating MCI and HC, AD and MCI, AD and HC as compared to whole hippocampus volume. These results suggested that we should explore the changes in the hippocampal subfields in subtypes of MCI or even at an earlier stage, that is subjective cognitive impairment.