Volumetric changes within hippocampal subfields in Alzheimer's disease continuum

Neurodegeneration in Alzheimer's disease continuum (ADC) starts from the transentorhinal cortex and progresses within hippocampal circuitry following the connectivity of its subfields transsynaptically. We aimed to track volumetric changes of the hippocampal subfields by comparing three stages of the ADC. MRI data of 15 patients diagnosed with Alzheimer's disease dementia (ADD), 15 patients with amnestic mild cognitive impairment (MCI), and 15 individuals with subjective cognitive impairment (SCI) were analyzed. The hippocampal formation was subdivided into CA1, CA3, subiculum (SUB), and dentate gyrus (DG) using FreeSurfer and volumetric values were obtained. The volumetric values were analyzed with ANCOVA and intracranial volume was selected as a covariate. ANCOVA results of the hippocampal subfields displayed statistically significant differences among the three groups in bilateral CA1, SUB, and DG volumes (Right CA1: F = 7.316, p = 0.002; left CA1: F = 6.768, p = 0.003; right SUB: F = 9.390, p < 0.001; left SUB: F = 5.925, p = 0.005; right DG: F = 9.469, p < 0.001; left DG: F = 9.354, p < 0.001), while CA3 volumes were not significantly different among the groups. Post hoc comparisons revealed that volume reductions in bilateral CA1, DG, and SUB were present in ADD compared to both MCI and SCI groups. No significant volumetric changes were found between the SCI and MCI groups. While our results are generally consistent with the literature in terms of the CA1 and SUB findings, they additionally point to the importance of the significant volume loss in DG and the resilience of the CA3 sector.