Understanding how different parts of the hippocampus shrink in Alzheimer’s disease (AD) patients can provide insight into their cognitive decline. While previous research has shown a link between overall hippocampal degeneration and memory problems, this study aimed to determine how specific parts of the hippocampus are affected and how this relates to cognitive decline in AD. Using high-resolution brain scans and neuropsychological tests, researchers examined 29 AD patients and 17 healthy individuals. The results revealed that the CA1, dentate gyrus, and subiculum regions of the hippocampus were significantly smaller in AD patients compared to healthy controls, while CA2 and CA3 were not affected. Furthermore, degeneration of the subiculum was associated with declines in overall cognitive function, while degeneration in CA1 and dentate gyrus was linked to declines in learning and memory. These findings suggest that assessing specific subfield atrophy patterns along with cognitive assessments could serve as a valuable prognostic tool for tracking disease progression in individuals on the AD spectrum.

IntroductionPeople with Alzheimer’s disease (AD) experience more rapid declines in their ability to form hippocampal-dependent memories than cognitively normal healthy adults. Degeneration of the whole hippocampal formation has previously been found to covary with declines in learning and memory, but the associations between subfield-specific hippocampal neurodegeneration and cognitive impairments are not well characterized in AD. To improve prognostic procedures, it is critical to establish in which hippocampal subfields atrophy relates to domain-specific cognitive declines among people along the AD spectrum. In this study, we examine high-resolution structural magnetic resonance imaging (MRI) of the medial temporal lobe and extensive neuropsychological data from 29 amyloid-positive people on the AD spectrum and 17 demographically-matched amyloid-negative healthy controls.MethodsParticipants completed a battery of neuropsychological exams including select tests of immediate recollection, delayed recollection, and general cognitive status (i.e., performance on the Mini-Mental State Examination [MMSE] and Montreal Cognitive Assessment [MoCA]). Hippocampal subfield volumes (CA1, CA2, CA3, dentate gyrus, and subiculum) were measured using a dedicated MRI slab sequence targeting the medial temporal lobe and used to compute distance metrics to quantify AD spectrum-specific atrophic patterns and their impact on cognitive outcomes.ResultsOur results replicate prior studies showing that CA1, dentate gyrus, and subiculum hippocampal subfield volumes were significantly reduced in AD spectrum participants compared to amyloid-negative controls, whereas CA2 and CA3 did not exhibit such patterns of atrophy. Moreover, degeneration of the subiculum along the AD spectrum was linked to a significant decline in general cognitive status measured by the MMSE, while degeneration scores of the CA1 and dentate gyrus were more widely associated with declines on the MMSE and tests of learning and memory.DiscussionThese findings provide evidence that subfield-specific patterns of hippocampal degeneration, in combination with cognitive assessments, may constitute a sensitive prognostic approach and could be used to better track disease trajectories among individuals on the AD spectrum.

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