Unveiling the Hippocampal Subfield Changes Across the Alzheimer’s Disease Continuum: a Systematic Review of Neuroimaging Studies

Studies exploring the hippocampal subfield atrophy in Alzheimer’s disease (AD) have shown contradictory results. This review aims to disentangle such heterogeneity by investigating the dynamic changes of hippocampal subfields across the AD continuum. We systematically searched the PubMed and EMBASE databases for case-control studies. Selected studies included investigations of biomarker-based amyloid status and reported data on hippocampal subfield atrophy using advanced MRI techniques. Twelve studies were included. Despite high heterogeneity, a distinguishable pattern of vulnerability of hippocampal subfields can be recognized from the cognitively unimpaired phase to the dementia stage, shedding light on hippocampal changes with disease progression. Consistent findings revealed atrophy in the subiculum and presubiculum, along with a potential increase in volume in the cornu ammonis (CA) among the cognitively unimpaired group, a feature not observed in patients experiencing subjective cognitive decline. Atrophy in the subiculum, presubiculum, CA 1–4, and the dentate gyrus characterized the mild cognitive impairment stage, with a more pronounced severity in the progression to dementia.