脑淀粉样血管病介导的阿尔茨海默病患者海马体积缩小。

Mediation of Reduced Hippocampal Volume by Cerebral Amyloid Angiopathy in Pathologically Confirmed Patients with Alzheimer's Disease.

机构信息

Department of Neurology, College of Medicine, University of Florida, Gainesville, FL, USA.

Laboratory for Rehabilitation Neuroscience, Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL, USA.

出版信息

J Alzheimers Dis. 2023;93(2):495-507. doi: 10.3233/JAD-220624.

DOI:10.3233/JAD-220624

PMID:37038809

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11952816/

Abstract

BACKGROUND

Hippocampal atrophy in cerebral amyloid angiopathy (CAA) has been reported to be similar to that in Alzheimer's disease (AD).

OBJECTIVE

To evaluate if CAA pathology partly mediates reduced hippocampal volume in patients with AD.

METHODS

Patients with a clinical diagnosis of AD and neuropathological confirmation of AD+/-CAA in the National Alzheimer's Coordinating Center database were included in the study. The volumes of temporal lobe structures were calculated on T1-weighted imaging (T1-MRI) using automated FreeSurfer software, from images acquired on average 5 years prior to death. Multivariate regression analysis was performed to compare brain volumes in four CAA groups. The hippocampal volume on T1-MRI was correlated with Clinical Dementia Rating sum of boxes (CDRsb) score, apolipoprotein E (APOE) genotype, and hippocampal atrophy at autopsy.

RESULTS

The study included 231 patients with no (n = 45), mild (n = 70), moderate (n = 67), and severe (n = 49) CAA. Among the four CAA groups, patients with severe CAA had a smaller mean left hippocampal volume (p = 0.023) but this was not significant when adjusted for APOE ɛ4 (p = 0.07). The left hippocampal volume on MRI correlated significantly with the hippocampal atrophy grading on neuropathology (p = 0.0003). Among patients with severe CAA, the left hippocampal volume on T1-MRI: (a) decreased with an increase in the number of APOE ɛ4 alleles (p = 0.04); but (b) had no evidence of correlation with CDRsb score (p = 0.57).

CONCLUSION

Severe CAA was associated with smaller left hippocampal volume on T1-MRI up to five years prior to death among patients with neuropathologically confirmed AD. This relationship was dependent on APOE ɛ4 genotype.

摘要

背景

脑淀粉样血管病（CAA）中的海马萎缩与阿尔茨海默病（AD）中的相似。

目的

评估 CAA 病理学是否部分介导了 AD 患者海马体积的减少。

方法

本研究纳入了国家阿尔茨海默病协调中心数据库中临床诊断为 AD 且 AD 伴或不伴 CAA 神经病理学确诊的患者。使用自动 Freesurfer 软件在 T1 加权成像（T1-MRI）上计算颞叶结构的体积，这些图像是在死亡前平均 5 年采集的。采用多元回归分析比较了四个 CAA 组的脑容量。T1-MRI 上的海马体积与临床痴呆评定量表总和分（CDRsb）评分、载脂蛋白 E（APOE）基因型以及尸检时的海马萎缩相关。

结果

本研究纳入了 231 名无（n=45）、轻度（n=70）、中度（n=67）和重度（n=49）CAA 的患者。在四个 CAA 组中，重度 CAA 患者的左侧海马平均体积较小（p=0.023），但在调整 APOE ɛ4 后无统计学意义（p=0.07）。MRI 上的左侧海马体积与神经病理学上的海马萎缩分级显著相关（p=0.0003）。在重度 CAA 患者中，T1-MRI 上的左侧海马体积：（a）随着 APOE ɛ4 等位基因数的增加而减少（p=0.04）；但（b）与 CDRsb 评分无相关性（p=0.57）。