Differential Atrophy in the Hippocampal Subfield Volumes in Four Types of Mild Dementia.

Lin Huang,Xiaochen Hu,Qihao Guo,Keliang Chen

doi:10.3389/fnins.2020.00699

Abstract

ObjectivesTo investigate the bilateral hippocampal subfield volumetric differences in four types of mild dementia, namely typical Alzheimer’s disease (tAD), dementia with Lewy bodies (DLB), semantic dementia (SD), and posterior cortical atrophy (PCA), to assist differential diagnosis.MethodsOne hundred three participants, including 22 tAD, 34 SD (17 left SD and 17 right SD), 15 DLB, 12 PCA patients, and 20 normal controls (NC), were recruited. All subjects received standard neuropsychological assessments and magnetic resonance imaging (MRI). The hippocampal subfields were automatically segmented via Freesurfer. The study compared the volumetric differences and used the receiver operating characteristic (ROC) curves to estimate the efficacy of each hippocampal subfield to distinguish between groups. Spearman correlation analysis was used to investigate the relationship between memory recall scores and hippocampal subfield volumes.ResultsThe hippocampal subfield atrophy varied in different groups: tAD, SD, and PCA patients had subregional atrophy in bilateral hippocampi compared to NC, and DLB patients showed preserved volumes; left SD patients suffered the most severe atrophy of the left hippocampus, and right SD patients were atrophied mostly in the right hippocampus. There was no significant difference in the volume of hippocampal subregions between tAD and PCA subjects, but the former tended to be atrophied more asymmetrically. ROC analysis showed that, for discrimination, the areas under the curve (AUC) of some subfields were larger than the total hippocampus, but none observed significant difference. In addition, immediate recall scores were correlated to left CA1, CA2/3, CA4/DG, subiculum, and presubiculum (p < 0.05), and delayed recall scores were strongly related to bilateral CA2/3, CA4/DG, subiculum, and presubiculum (r = 0.38–0.52, p < 0.05).ConclusionDifferential atrophy patterns in the bilateral hippocampal subfield volumes could serve the differential diagnosis in patients with different causes of mild dementia: left CA1 for tAD; left presubiculum for LSD; right CA4/DG, right presubiculum, and right subiculum for RSD; CA4/DG and right CA2/3 for DLB; right CA2/3 and right CA4/DG for PCA. Additionally, several hippocampal subfield volumes were significantly associated with memory scores, further highlighting the essential role of the hippocampus in memory decline.

Highlights

Structural magnetic resonance imaging (MRI) and volumetric studies can be helpful in the differential diagnosis by demonstrating focal changes in the brain volumes with different causes of dementia
The results addressed in particular (Mu and Gage, 2011) typical Alzheimer’s disease (tAD), left SD (LSD), right SD (RSD), and Posterior cortical atrophy (PCA) patients had widespread subregional atrophy in bilateral hippocampi compared to normal controls (NC) while the volume of the bilateral hippocampi and subfields tended to be preserved in Dementia with Lewy bodies (DLB) patients; (Hatanpaa et al, 2014) among all groups, atrophy of the left hippocampal subfields in the LSD group was the most serious of all, and RSD patients were the most severely atrophied in the right hippocampus; (Freundl and Buzsi, 2015) no significant difference was found in the volume of subregions between tAD and PCA patients
Using an automated image analysis pipeline to explore the subfields of the hippocampus, our study reveals that patients with tAD, LSD, RSD, DLB, and PCA have different atrophy patterns in bilateral hippocampi at mild stages of dementia

Summary

Introduction

Structural magnetic resonance imaging (MRI) and volumetric studies can be helpful in the differential diagnosis by demonstrating focal changes in the brain volumes with different causes of dementia. The hippocampus consists of several anatomically and functionally diverse subfields, including the dentate gyrus (DG), the cornu ammonis (CA) areas 1–4, the subiculum, and the presubiculum (Freundl and Buzsi, 2015). These subfields might be selectively damaged in patients with different causes of dementia. A recent study comparing 30 AD patients, 41 MCI patients, and 38 healthy controls with an automated segmentation protocol for the volumetric analysis of hippocampal subfields reports a prevalent atrophy of the presubicular-subicular complex from the early phases of AD (Carlesimo et al, 2015). Given the complexity of the internal structure of the hippocampus, the different patterns of hippocampal subfield atrophy in different dementias has not been clarified

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