Abstract
The heterogeneous specialisation of hippocampal subfields across memory functions has been widely shown in animal models. Yet, few in vivo studies in humans have explored correspondence between hippocampal subfield anatomy and memory performance in ageing. Here, we used a well-validated automated MR segmentation protocol to measure hippocampal subfield volumes in 436 non-demented adults aged 50+. We explored relationships between hippocampal subfield volume and verbal episodic memory, as indexed by word list recall at immediate presentation and following delay. In separate multilevel models for each task, we tested linearity and non-linearity of associations between recall performance and subfield volume. Fully-adjusted models revealed that immediate and delayed recall were both associated with cubic fits with respect to volume of subfields CA1, CA2/3, CA4, molecular layer, and granule cell layer of dentate gyrus; moreover, these effects were partly dissociable from quadratic age trends, observed for subiculum, molecular layer, hippocampal tail, and CA1. Furthermore, analyses of semantic fluency data revealed little evidence of robust associations with hippocampal subfield volumes. Our results show that specific hippocampal subfields manifest associations with memory encoding and retrieval performance in non-demented older adults; these effects are partly dissociable from age-related atrophy, and from retrieval of well-consolidated semantic categories.
Highlights
Hippocampus is among the most important brain structures involved in memory[1,2,3], and is a critical site of pathogenesis in dementing illnesses such as Alzheimer’s Disease[4,5,6,7]
We predicted relationships would emerge between verbal episodic memory and volumes of subfields CA1, CA2/3, CA4, and granule cell layer of dentate gyrus (GC-DG) – regions heavily implicated in encoding and retrieval processes[12,35]
Iterative addition of immediate recall (IR) interaction terms to the fully adjusted model revealed that the cubic IR terms and their interaction with subfield significantly improved the model fit, over quadratic (likelihood ratio [LR] test: χ2(11) = 555.6, p < 0.00001) and linear (LR: χ2(22) = 565.8, p < 0.00001) IR and their subfield interaction terms in the model
Summary
Hippocampus is among the most important brain structures involved in memory[1,2,3], and is a critical site of pathogenesis in dementing illnesses such as Alzheimer’s Disease[4,5,6,7]. Until recently, very few in vivo studies in humans had shown dissociable relationships between performance in different memory domains and hippocampal subfield anatomy or function[13,14,15]. Despite this, there remains a limited understanding of the role of hippocampal subfields in other memory domains relied on in daily life, such as verbal episodic memory (e.g., recalling a grocery list) or semantic memory (e.g., retrieving familiar nouns) [but see17]. Non-demented sample of community-dwelling older adults, we aimed to dissociate memory domains based on their expected patterning with hippocampal subfield volumes. We expected that fluency in semantic memory (retrieval of familiar category names) would show little if any relationship with subfield volumes[19]. We appraised these relationships in tandem with age-related differences in subfield volumes, by assessing the robustness of effects related to memory alongside fits for cross-sectional age
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