Evaluating the position of the uncal apex as a predictor of episodic memory across the adult lifespan

Abstract

AbstractStructural decline of the hippocampus occurs in heterogeneous patterns across its spatial extent, and is an important determinant of episodic memory dysfunction in aging. However, evidence indicate that the anatomical landmark uncal apex, used to demarcate anterior and posterior hippocampal subregions, changes position as the hippocampus atrophies. This emphasizes a risk of misclassifying gray matter into the incorrect subregion when using standard demarcation methods, contributing to over- and underestimation of age effects on anterior and posterior hippocampal volume. Yet, it remains unexplored whether inter-individual differences in uncal apex position predict episodic memory performance in itself. Here, we manually identified the uncal apex in anatomical MRI data from a healthy adult-lifespan sample (n=180; 20-79 years), assessed age differences in its position, and associations with word recollection performance. Increasing age was linked to a more anteriorly located uncal apex (retracting ∼0.041 mm/year). Importantly, a more anterior uncal apex position was linked to lower memory performance. Whereas anterior hippocampal volume remained stable with increasing age, posterior volume displayed non-linear decline with an infliction point at approximately 45 years. Neither anterior nor posterior hippocampal volumes predicted memory performance, but the ratio of posterior to anterior volume showed a significant association with memory when taking the position of the uncal apex into account. These results indicate that uncal apex position may provide an estimate of hippocampal integrity sensitive to inter-individual differences in memory, independent of limitations associated with different segmentation methods.