Differential associations of age with volume and microstructure of hippocampal subfields in healthy older adults

Abstract

Hippocampal atrophy in advanced healthy aging has frequently been reported. However, the vulnerability of different hippocampal subfields to age-related atrophy is still a source of debate. Moreover, the association of age with the microstructural integrity of subfields is largely unknown. In this study, we investigated the associations between age and volume as well as microstructural integrity of hippocampal subfields using a three-dimensional (3D) surface mapping approach. Forty-three healthy older adults spanning the age range from 60 to 85 years underwent T1-weighted and diffusion-tensor imaging. Analyses demonstrated an association of age with hippocampal volume predominantly in the most anterior part of the hippocampal head, mainly corresponding to the subiculum. In contrast, the association of age with hippocampal microstructural integrity was mainly confined to regions located in the hippocampal body and tail, corresponding to the subiculum and CA1. Results indicate that age-related volumetric and microstructural alterations within hippocampal subfields provide complementary information and reflect different age-related processes. Potential mechanisms underlying the differential associations of age with volume and microstructure of hippocampal subfields are discussed.

Lifespan trajectories and relationships to memory of the macro- and microstructure of the anterior and posterior hippocampus – a longitudinal multi-modal imaging study

“…The age-relationships of volume and MD were not weakened the least by including both in the same model. Even though not previously addressed in a lifespan sample, this finding is in line with previous studies showing that micro- and macrostructural measures of hippocampal subfields are complementary in their aging-relationships (Pereira et al, 2014; Wolf et al, 2015). Thus, the cellular processes responsible for the micro-and macro-structural changes in hippocampal sub-regions across life appear to be completely unrelated.…”

“…Both aHC and pHC volume and MD were strongly and independently related to age through the lifespan, with better model fits for aHC suggesting a somewhat tighter relationship with age. While studies of adults have shown increases in hippocampal MD with age (Anblagan et al, 2018); den Heijer et al (2012); (Pereira et al, 2014; Wolf et al, 2015), we are not aware of any lifespan studies of hippocampal microstructure. The volumetric findings are in line with previous developmental studies showing differential (DeMaster et al, 2014; Lin et al, 2013; Riggins et al, 2018; Wang et al, 2003; Yang et al, 2013) and non-linear (Daugherty et al, 2017; Gogtay et al, 2006) age-relationships for sub-regions along the AP axis.…”

“…Several of these will likely affect water diffusion in hippocampal tissue, which can be measured by diffusion tensor imaging (DTI). Evidence so far suggests that higher mean diffusivity (MD) in the hippocampus is positively related to aging (den Heijer et al, 2012; Pereira et al, 2014; Wolf, Fischer, de Flores, Chetelat, & Fellgiebel, 2015), increases over time in older adults (Anblagan et al, 2018) and correlates more strongly with poorer memory function than hippocampal volume (Aribisala et al, 2014; Carlesimo, Cherubini, Caltagirone, & Spalletta, 2010; den Heijer et al, 2012; van Norden et al, 2012). Evidence also suggests that hippocampal MD and volume could be inversely related, with studies reporting nominal negative correlations that usually are not statistically significant (Anblagan et al, 2018; den Heijer et al, 2012; Pereira et al, 2014).…”

“…Evidence also suggests that hippocampal MD and volume could be inversely related, with studies reporting nominal negative correlations that usually are not statistically significant (Anblagan et al, 2018; den Heijer et al, 2012; Pereira et al, 2014). Although few studies have directly tested micro- vs. macro-structural measures of hippocampal subfields, the tendency seems to be that they are related but complimentary in their aging-relationships (Pereira et al, 2014; Wolf et al, 2015). We could not find any published studies of hippocampal MD changes along the AP axis in development.…”

Associations of hippocampal subfields in the progression of cognitive decline related to Parkinson's disease

“…The Bayesian inferential method deployed on FreeSurfer 6.0 has not been robustly validated against a gold standard method, such as manual segmentation (Wolf et al, 2015). Furthermore, even with ultra-high resolution MRI, there are boundaries such as the interfaces between the CA fields along the pyramidal layer of the hippocampus or the CA4/GC-DG interface that cannot be seen.…”