Background: The hippocampus and hippocampal subfields have been found to be diversely affected in Alzheimer’s Disease (AD) and early stages of Alzheimer’s disease by neuroimaging studies. However, our knowledge is still lacking about the trajectories of the hippocampus and hippocampal subfields atrophy with the progression of Alzheimer’s disease.

Objective: To identify which subfields of the hippocampus differ in the trajectories of Alzheimer’s disease by magnetic resonance imaging (MRI) and to determine whether individual differences on memory could be explained by structural volumes of hippocampal subfields.

Methods: Four groups of participants including 41 AD patients, 43 amnestic mild cognitive impairment (aMCI) patients, 35 subjective cognitive decline (SCD) patients and 42 normal controls (NC) received their structural MRI brain scans. Structural MR images were processed by the FreeSurfer 6.0 image analysis suite to extract the hippocampus and its subfields. Furthermore, we investigated relationships between hippocampal subfield volumes and memory test variables (AVLT-immediate recall, AVLT-delayed recall, AVLT-recognition) and the regression model analyses were controlled for age, gender, education and eTIV.

Results: CA1, subiculum, presubiculum, molecular layer and fimbria showed the trend toward significant volume reduction among four groups with the progression of Alzheimer’s disease. Volume of left subiculum was most strongly and actively correlated with performance across AVLT measures.

Conclusion: The trend changes in the hippocampus subfields and further illustrates that SCD is the preclinical stage of AD earlier than aMCI. Future studies should aim to associate the atrophy of the hippocampal subfields in SCD with possible conversion to aMCI or AD with longitudinal design.