Structural imaging of hippocampal subfields in healthy aging and Alzheimer’s disease

Abstract

Hippocampal atrophy, as evidenced using magnetic resonance imaging (MRI), is one of the most validated, easily accessible and widely used biomarkers of Alzheimer's disease (AD). However, its imperfect sensitivity and specificity have highlighted the need to improve the analysis of MRI data. Based on neuropathological data showing a differential vulnerability of hippocampal subfields to AD processes, neuroimaging researchers have tried to capture corresponding morphological changes within the hippocampus. The present review provides an overview of the methodological developments that allow the assessment of hippocampal subfield morphology in vivo, and summarizes the results of studies looking at the effects of AD and normal aging on these structures. Most studies highlighted a focal atrophy of the CA1 subfield in the early (predementia or even preclinical) stages of AD, before atrophy becomes more widespread at the dementia stage, consistent with the pathological literature. Preliminary studies have indicated that looking at this focal atrophy pattern rather than standard whole hippocampus volumetry improves diagnostic accuracy at the mild cognitive impairment (MCI) stage. However, controversies remain regarding changes in hippocampal subfield structure in normal aging and regarding correlations between specific subfield volume and memory abilities, very likely because of the strong methodological variability between studies. Overall, hippocampal subfield analysis has proven to be a promising technique in the study of AD. However, harmonization of segmentation protocols and studies on larger samples are needed to enable accurate comparisons between studies and to confirm the clinical utility of these techniques.

Individual differences in associative memory among older adults explained by hippocampal subfield structure and function

“…If individual subfields are differentially vulnerable to age-related change, then averaging activity across regions could produce variable findings. Importantly, research in aged rodents suggests focal changes, indicating selective synaptic weakening among perforant path inputs from ERC to DG and CA3, as well as representational rigidity in CA3 place cells (8,9,11).…”

“…We aimed to determine whether variability in associative memory performance could be explained by variability in a specific combination of structural and functional metrics. Based on prior structural findings, we hypothesized that ERC (15)(16)(17)(18)(19) and CA1-SRLM (11,28) thickness would be positively linked to associative memory performance. Motivated by prior functional findings, we hypothesized that taskrelated activity in DG/CA3 (31,(33)(34)(35) and ERC (36)(37)(38)(39)(40)(41) would be negatively linked to associative memory performance.…”

“…1A). Moreover, evidence in rodents and humans suggests that these subfields are differentially affected by age, as well as by age-related disease (8,9,11).…”

“…Similarly, in vivo imaging studies of patients with mild cognitive impairment (MCI) (a clinical precursor to AD) and mild AD demonstrate focal atrophy in ERC (23)(24)(25) and CA1 (e.g., ref. 26), although some studies demonstrate targeted atrophy of subiculum or broader atrophy in multiple hippocampal subfields (11).…”

P2‐231: Systematic Comparison of Different Techniques to Measure Hippocampal Subfield Volumes in ADNI2

“…These techniques were applied to a variety of diseases in small single-site studies and usually found subfield volumetry to be superior to standard whole hippocampal volumetry for the detection of hippocampal damage in the early stages of the disease process, for differentiating between diseases or for the investigation of structure/function relationships (e.g., Wang et al, 2006;Ballmaier et al, 2008;Mueller et al, 2008;Schobel et al, 2009;Neylan et al, 2010;Bender et al, 2013;Kerchner et al, 2014;SchoeneBake et al, 2014;Chao et al, 2014;Hsu et al, 2015;De Flores et al, 2015;Pluta et al, 2012;Yushkevich et al, 2015b). The promise of hippocampal subfield volumetry techniques however led to two unexpected developments that could potentially limit the usefulness of this approach.…”