Uncal apex position varies with normal aging

Abstract

The uncal apex is an anatomical landmark frequently used for segmenting the hippocampus into its anterior and posterior segments, a necessary step for computing many measurements of its long axis. It functions well, as it is both local to the hippocampus and easy to identify. However, in spite of widespread use and definition in the EADC‐ADNI Harmonized Hippocampal Protocol (HarP), how the uncal apex is influenced by gross hippocampal changes during normal aging has not been established, nor has the possible impact on measures of anterior hippocampus (aHPC) and posterior hippocampus (pHPC) volume. Here I drew upon three large data sets to describe and confirm these relationships, investigating them in one large data set and replicating my findings in the two others, evaluating a total of 4,434 hippocampi. I found the uncal apex fell in an increasingly more anterior position with increasing age. This age‐related retraction of the uncus began after age 36, with the sharpest effects arising after age 60. This phenomenon exaggerates age‐related aHPC volume decreases while simultaneously underestimating age‐related pHPC volume decreases, a pattern I confirmed by juxtaposing uncal apex and MNI space‐based landmarking. A hippocampally based reference frame was also rendered unstable by age‐related shifts in the posterior extent of the hippocampus. Both the uncal apex and hippocampal reference frame should therefore be used with caution in aging research, or in research involving other demographic or disease factors known to evoke gross changes in the hippocampus. Instead, MNI coordinate‐based heuristics may be appropriate for segmenting the hippocampus in study designs involving such factors. Apex‐based segmentation is still attractive, however, in study designs where advanced age and atrophy are not used as regressors, including investigations into long‐axis effects in healthy young adults. Progress toward localizing functional divisions within the hippocampus is needed to identify best practices for the field.

High resolution diffusion tensor imaging of the hippocampus across the healthy lifespan

“…Although it has clear advantages over automated methods, manual segmentation of the hippocampus into the head/body/tail by way of external landmarks (Olsen et al, 2019) is still limited by age‐related changes in the positions of these landmarks. For instance, the uncal apex has been shown to move in the anterior direction from 18 to 87 years, a change which can effectively reduce hippocampal head volume and increase body volume (Poppenk, 2020). A continuous evaluation along the axis would be ideal, though diffusion metrics are less affected by these divisions than measures of volume.…”

Hippocampal volume and navigational ability: The map(ping) is not to scale

“…Posterior to anterior hippocampal comparisons also depend critically on how one defines the anterior vs. posterior hippocampus. There are several different ways to identify the anterior hippocampus as distinct from the posterior hippocampus including the presence of the collateral sulcus and the uncal apex (Duvernoy et al, 2013;Poppenk, 2020). Identifying the uncal apex is one of the more common ways to segment the hippocampus into anterior, medial, and posterior sections and was employed in the original Poppenk and Moscovitch (2011) study as well as Weisberg and colleagues (2019) in exploratory analyses.…”

“…Identifying the uncal apex is one of the more common ways to segment the hippocampus into anterior, medial, and posterior sections and was employed in the original Poppenk and Moscovitch (2011) study as well as Weisberg and colleagues (2019) in exploratory analyses. An issue, however, is that identification of the apex is variable with age (Poppenk, 2020), raising the question if white matter tracts or other brain-wide changes may be producing some of the variability in anterior vs. hippocampal volume. Indeed, as we will explore in the next sections, white matter and connectivity differences are also strong candidates for mediating navigation skill.…”

An axis-referenced morphometric model reshaping the hippocampus following its longitudinal organization

“…As a result, the correspondence established based on proportions is no longer valid, even if the effect may not so extreme. In (Poppenk J et al, 2020), the author describes a similar mis-correspondence example that due to the contraction of the uncus, a larger portion of anterior is redefined as posterior of hippocampus, leading to incorrect conclusion that the posterior segments grow. One possible solution is to use the long axis of the healthy hippocampus, and fit the corresponded ARMM coordinates directly to the atrophied hippocampus to the same subject, followed by eroding extra elements outside the boundary surface (i.e., using the longitudinal strategy proposed in this paper).…”