Studying APOE ɛ4 Allele Dose Effects with a Univariate Morphometry Biomarker.
Studying APOE ɛ4 Allele Dose Effects with a Univariate Morphometry Biomarker.
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DOI：
10.3233/jad-215149
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发表时间：
2022
影响因子：
4
通讯作者：
Wang, Yalin
中科院分区：
文献类型：
--
作者：
Wang, Gang;Zhou, Wenju;Kong, Deping;Qu, Zongshuai;Ba, Maowen;Hao, Jinguang;Yao, Tao;Dong, Qunxi;Su, Yi;Reiman, Eric M.;Caselli, Richard J.;Chen, Kewei;Wang, Yalin
关键词：
本文提出了一种子空间分解方法，该方法能够利用单变量形态测量生物标志物来表示与阿尔茨海默病（AD）的 APOE-e4 遗传风险相关的海马形态变化，该方法基于老年认知未受损（CU）个体的磁共振成像（MRI）数据。等级最小化和稀疏约束理论驱动我们的方法。采用秩最小化机制结合改进的部分奇异值分解(SVD)来提取群体公共结构，降低大规模矩阵SVD的计算成本。此外，考虑海马萎缩区域的局部连续性的稀疏约束被应用于恢复个体形态差异。基于淀粉样蛋白-β (Aβ) 阳性 AD 患者和 Aβ 阴性 CU 受试者的群体共同结构，我们确定了感兴趣区域 (ROI)，其反映了 AD 发展引起的显着形态测量变化。然后根据这些 ROI 构建单变量形态测量指数 (UMI)。利用大量具有2个、1个和无APOE-e4等位基因的认知功能未受损的中老年晚期成年人的研究，我们设置了三个实验来研究纵向APOE-e4纯合子（HM，N=30）、杂合子（HT，N=49）和非携带者（NC，N=49）海马形态变化的差异。 N=61）。结果表明，与我们之前的工作相比，所提出的 UMI 具有更高的计算效率，并且表现出比原始表面和体积测量更重要的识别 APOE-e4 剂量效应的能力。我们的工作可能会提供一种具有成本效益的 UMI，帮助评估 AD 负担、进展和对干预措施的反应，从而有可能促进 AD 临床试验的注册。
This paper proposes a subspace decomposition method capable of exploiting a univariate morphometry biomarker to represent the hippocampal morphological changes associated with APOE-e4 genetic risk for Alzheimer’s disease (AD) based on magnetic resonance imaging (MRI) data of the elderly cognitively unimpaired (CU) individuals. Rank minimization and sparsity constraint theory drive our method. Rank minimization mechanism combined with improved partial singular value decomposition (SVD) is used to extract group common structures and reduce the computational cost of SVD of the large-scale matrix. Further, sparse constraint considering the local continuity of the hippocampal atrophy regions is applied to recover individual morphological differences. Based on the group common structures of amyloid-β (Aβ) positive AD patients and Aβ negative CU subjects, we identified the regions-of-interest (ROI), which reflect significant morphometry changes caused by the AD development. Then univariate morphometry index (UMI) is constructed from these ROIs. Capitalizing on the study of a large number of cognitively unimpaired late middle-aged and older adults with two, one, and no APOE-e4 alleles, we set up three experiments to study the differences of hippocampal morphological changes among the longitudinal APOE-e4 homozygotes (HM, N=30), heterozygotes (HT, N=49) and non-carriers (NC, N=61). The results show that the proposed UMI enjoys improved computational efficiency comparing to our prior work and demonstrates a more vital ability to identify APOE-e4 dose effects than the raw surface and volume measurements. Our work may provide a cost-effective UMI that helps evaluate AD burden, progression, and response to interventions, potentially facilitating AD clinical trial enrollments.