Polygenic Hazard Score Associated Multimodal Brain Networks Along the Alzheimer's Disease Continuum.
Polygenic Hazard Score Associated Multimodal Brain Networks Along the Alzheimer's Disease Continuum.
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DOI：
10.3389/fnagi.2021.725246
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发表时间：
2021
影响因子：
4.8
通讯作者：
Calhoun VD
中科院分区：
文献类型：
--
作者：
Li K;Fu Z;Qi S;Luo X;Zeng Q;Xu X;Huang P;Zhang M;Calhoun VD
晚发性阿尔茨海默病（AD）是一种多基因神经退行性疾病。识别AD遗传易感性背后的神经影像学表型对于理解AD发病机制至关重要。先前的研究已经导致了两个主要问题：（1）一般的“多基因危险评分”（PHS）是一个很好的选择，以确定个人的遗传风险为AD;（2）研究人员是否还应包括模态间的关系，考虑到这些可能提供补充信息的AD病因分析。我们收集了88名健康对照，77名轻度认知障碍（MCI）患者和22名AD患者，以模拟ADNI数据库中的AD连续体。PHS引导的多模态融合被用来研究PHS对AD连续体中多模态脑网络的影响，通过最大化模态间关联和参考模态相关性。低频波动的分数振幅、灰质（GM）体积和淀粉样蛋白标准摄取值比值被纳入神经影像学特征。最后，神经影像学特征的变化沿着AD连续体进行了调查，并建立认知性能和识别PHS相关的多模态组件之间的关系。我们发现PHS与多模态脑网络相关，在淀粉样蛋白沉积增加的情况下，多模态脑网络表现出不同的功能和结构损伤。值得注意的是，沿着AD进展，功能损害发生在GM萎缩之前，淀粉样蛋白沉积从MCI阶段开始并在整个疾病连续体中进行性增加。PHS与AD连续体沿着多方面脑损伤相关，包括认知功能障碍、病理沉积，这可能是AD发病机制的基础。
Late-onset Alzheimer’s disease (AD) is a polygenic neurodegenerative disease. Identifying the neuroimaging phenotypes behind the genetic predisposition of AD is critical to the understanding of AD pathogenesis. Two major questions which previous studies have led to are: (1) should the general “polygenic hazard score” (PHS) be a good choice to identify the individual genetic risk for AD; and (2) should researchers also include inter-modality relationships in the analyses considering these may provide complementary information about the AD etiology. We collected 88 healthy controls, 77 patients with mild cognitive impairment (MCI), and 22 AD patients to simulate the AD continuum included from the ADNI database. PHS-guided multimodal fusion was used to investigate the impact of PHS on multimodal brain networks in AD-continuum by maximizing both inter-modality association and reference-modality correlation. Fractional amplitude of low frequency fluctuations, gray matter (GM) volume, and amyloid standard uptake value ratios were included as neuroimaging features. Eventually, the changes in neuroimaging features along AD continuum were investigated, and relationships between cognitive performance and identified PHS associated multimodal components were established. We found that PHS was associated with multimodal brain networks, which showed different functional and structural impairments under increased amyloid deposits. Notably, along with AD progression, functional impairment occurred before GM atrophy, amyloid deposition started from the MCI stage and progressively increased throughout the disease continuum. PHS is associated with multi-facets of brain impairments along the AD continuum, including cognitive dysfunction, pathological deposition, which might underpin the AD pathogenesis.
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DOI：
10.1109/tsp.2009.2021636
发表时间：
2009-10-01
期刊：
IEEE transactions on signal processing : a publication of the IEEE Signal Processing Society
影响因子：
--
作者：
Li YO;Adalı T;Wang W;Calhoun VD
通讯作者：
Calhoun VD
影响因子：
4.3
作者：
Kauppi K;Fan CC;McEvoy LK;Holland D;Tan CH;Chen CH;Andreassen OA;Desikan RS;Dale AM;Alzheimer's Disease Neuroimaging Initiative
通讯作者：
Alzheimer's Disease Neuroimaging Initiative
影响因子：
5.1
作者：
Li, Jie-Qiong;Wang, Hui-Fu;Yu, Jin-Tai
通讯作者：
Yu, Jin-Tai
影响因子：
3.7
作者：
Mormino, Elizabeth C.;Smiljic, Andre;Jagust, William J.
通讯作者：
Jagust, William J.
影响因子：
5.2
作者：
Andrews-Hanna JR;Smallwood J;Spreng RN
通讯作者：
Spreng RN