AbstractDepressive symptoms occur commonly in Alzheimer’s disease (AD). Although abnormalities in the amygdala-frontal circuit have been linked to emotional dysregulation and cognitive impairment, the neurological basis underlying these associations in AD patients with depressive symptoms (ADD) is unclear.

摘要抑郁症状常见于阿尔茨海默病（AD）。尽管杏仁核-额叶回路异常与情绪失调和认知障碍有关，但AD患者抑郁症状（ADD）中这些关联的神经基础尚不清楚。

We aimed to investigate the relationship between the amygdala-frontal circuit and depressive symptoms and cognitive function in ADD. We recruited 60 ADD, 60 AD patients without depressive symptoms (ADND), and 60 healthy controls (HC). Functional connectivity (FC) maps of the bilateral amygdala were compared.

我们旨在调查ADD中杏仁核-额叶回路与抑郁症状和认知功能之间的关系。我们招募了60名ADD，60名无抑郁症状（ADND）的AD患者和60名健康对照（HC）。比较双侧杏仁核的功能连接（FC）图。

Fractional anisotropy (FA) of the amygdala-frontal circuit connected by the uncinate fasciculus (UF) was calculated using automated fiber quantification (AFQ). In addition, mediation analysis was performed to explore the effects of the amygdala-frontal circuit on the relationship between depressive symptoms and cognitive function.

使用自动纤维定量（AFQ）计算由钩状束（UF）连接的杏仁核额叶回路的分数各向异性（FA）。此外，还进行了中介分析，以探讨杏仁核-额叶回路对抑郁症状与认知功能之间关系的影响。

We found decreased bilateral amygdala FC with the inferior frontal gyrus (IFG) in the ADD group compared to the ADND and HC groups. Moreover, FA in the left frontal UF (nodes 64–97) was significantly lower in the ADD group than ADND group. Notably, amygdala-based FC with IFG and the left frontal UF FA mediated the relationship between depressive symptoms and cognitive function in ADD, with mediating effects ranging between 15 and 18%.

与ADND和HC组相比，我们发现ADD组双侧杏仁核FC与额下回（IFG）减少。此外，ADD组左额叶UF（节点64-97）的FA显着低于ADND组。。

Our study is the first to demonstrate the mediating effect of functional and microstructural abnormalities in the amygdala-frontal circuit in ADD. The findings suggest that the amygdala-frontal circuit may underlie emotional dysregulation in ADD, providing potential targets for treatment strategies..

我们的研究首次证明了ADD中杏仁核-额叶回路功能和微观结构异常的介导作用。研究结果表明，杏仁核-额叶回路可能是ADD情绪失调的基础，为治疗策略提供了潜在的目标。。

IntroductionAlzheimer’s disease (AD) is a neurodegenerative disorder with the primary clinical manifestation of cognitive impairment [1]. Moreover, up to 80% of patients with AD also exhibit behavioral and psychological symptoms of dementia (BPSD) [2]. Depressive symptoms are among the most common BPSD in AD patients, with a prevalence ranging from 37 to 46% [3].

引言阿尔茨海默病（AD）是一种神经退行性疾病，主要临床表现为认知障碍（1）。此外，高达80%的AD患者也表现出痴呆（BPSD）的行为和心理症状（2）。抑郁症状是AD患者中最常见的BPSD之一，患病率从37%到46%不等（3）。

Evidence that depressive symptoms are associated with more impaired cognitive function and faster subsequent cognitive decline [4]. Considering the high prevalence and poor prognosis of depressive symptoms in AD, the pathophysiological mechanisms of depressive symptoms and cognitive function need to be explored.

有证据表明抑郁症状与认知功能受损和随后认知能力下降更快有关（4）。考虑到AD中抑郁症状的高患病率和预后不良，需要探索抑郁症状和认知功能的病理生理机制。

The amygdala-frontal circuit involves emotional dysregulation and cognitive integration, the microstructural and functional abnormalities of this circuit are strongly associated with both depression and AD [5]. However, it is not clear how functional and microstructural alterations in the amygdala-frontal circuit contribute to depressive symptoms in AD.Resting-state functional magnetic resonance imaging (rs-fMRI) is a non-invasive technique to examine the neural connectivity of the human brain [6].

杏仁核-额叶回路涉及情绪失调和认知整合，该回路的微观结构和功能异常与抑郁症和AD密切相关（5）。然而，目前尚不清楚杏仁核-额叶回路的功能和微观结构改变如何导致AD的抑郁症状。静息状态功能磁共振成像（rs-fMRI）是一种非侵入性技术，用于检查人脑的神经连接性〔6〕。

Seed-based functional connectivity (FC) could reflect stimulus-independent temporal correlations of neuronal activity patterns between the seed with other spatially segregated brain areas [7]. One previous fMRI study found that AD patients with depressive symptoms (ADD) showed decreased amygdala-based FC with medial prefrontal cortex and inferior frontal gyrus (IFG) compared to AD patients without depressive symptoms (ADND) [8], which may reflect impaired amygdala-frontal circuit leading to abnormal emotional regulation in ADD.

。先前的一项功能磁共振成像研究发现，与没有抑郁症状（ADND）的AD患者相比，患有抑郁症状（ADD）的AD患者表现出基于杏仁核的FC减少，内侧前额叶皮层和额下回（IFG）[8]，这可能反映了杏仁核-额叶回路受损，导致ADD异常情绪调节。

Current neuroimaging studies have found that abnormal amygdala FC with brain regio.

目前的神经影像学研究发现杏仁核FC异常与大脑区域有关。

Data availability

数据可用性

The data that support the findings of this study are available from the corresponding author upon reasonable request.

根据合理的要求，通讯作者可以提供支持本研究结果的数据。

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Jacob Y，Morris LS，Verma G，Rutter SB，Balchandani P，Murrough JW。重性抑郁症中海马和杏仁核亚区连接体层次的改变。Transl精神病学。2022年；12https://doi.org/10.1038/s41398-022-01976-0.Download参考文献资助本研究得到了上海市科学技术委员会（22DZ2205800），国家自然科学基金委员会（81671402），上海市第五轮公共卫生三年行动计划（GWV-9.2），国家重点研发计划（2017YFC1310500）的资助。作者信息作者和附属机构上海交通大学医学院上海精神卫生中心老年精神病学系，上海，中国杨杜，张少伟，齐秋，袁芳，赵璐，凌跃，王京华，冯燕和夏立德浙江大学医学院第一附属医院精神科，杭州，中国杨杜作者杨杜作者出版物你也可以在中搜索这位作者。

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PubMed Google ScholarContributionsXL and YD conceived and designed the study. YD, SWZ, LZ, and QQ acquired and analyzed the data. LY, YF, and JHW performed and checked the image quality of amygdala segmentation. YD, FY, and XL interpreted the results. YD and JY drafted the manuscript.

PubMed Google ScholarContributionsXL和YD构思并设计了这项研究。YD，SWZ，LZ和QQ获取并分析了数据。LY，YF和JHW执行并检查了杏仁核分割的图像质量。YD，FY和XL解释了结果。YD和JY起草了手稿。

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Reprints and permissionsAbout this articleCite this articleDu, Y., Zhang, S., Qiu, Q. et al. The mediating effect of the amygdala-frontal circuit on the association between depressive symptoms and cognitive function in Alzheimer’s disease.

转载和许可本文引用本文Du，Y.，Zhang，S.，Qiu，Q。等人。杏仁核-额叶回路在阿尔茨海默病抑郁症状与认知功能之间的中介作用。

Transl Psychiatry 14, 301 (2024). https://doi.org/10.1038/s41398-024-03026-3Download citationReceived: 14 September 2023Revised: 14 July 2024Accepted: 16 July 2024Published: 23 July 2024DOI: https://doi.org/10.1038/s41398-024-03026-3Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

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