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ORIGINAL RESEARCH article

Front. Neurol.

Sec. Applied Neuroimaging

Study on the Relationship Between Insomnia Disorder, PET/CT, and Gut Microbiota in Patients with Alzheimer's Disease

Provisionally accepted
Jian  KangJian KangJianwen  ChenJianwen ChenPeixue  LiPeixue LiShiqi  ZhaoShiqi ZhaoFangfang  JingFangfang JingJinghui  XieJinghui XieChunbo  DongChunbo Dong*
  • The First Affiliated Hospital of Dalian Medical University, Dalian, China

The final, formatted version of the article will be published soon.

Objective: Previous studies on Alzheimer's disease (AD) have focused on the relationships between brain pathology and gut microbiota, brain pathology and sleep, and sleep and gut microbiota, but no study has explored the relationship between these three factors. Therefore, we integrated these three factors into a unified framework and aimed to provide a reference for treating insomnia disorders (ID) in patients with AD. Patients/Methods: The 65 patients diagnosed with AD were categorized into ID group (n = 30) and non-ID group (n = 35) according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality. 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) and 18F-florbetapir (AV45)-PET scan were performed. Fecal samples were analyzed using 16S rRNA amplicon sequencing. Basic data, PET, and gut microbiota were compared between the ID and non-ID groups. Finally, the relationships among the data, with differences including PSQI, were analyzed. All p-values were corrected using the False Discovery Rate (FDR) method to obtain q-values. Results: Data with significant differences (p < 0.05 or q < 0.05) included PSQI, left middle frontal cortex-FDG, left Broca's area-FDG, right thalamus (rTh)-FDG, left thalamus (lTh)-FDG, Roseburia, Prevotella 7, and Bifidobacterium. However, no differences were found between groups in AV45-PET. In the ID group, PSQI scores were significantly correlated with rTh-FDG (r = -0.612, q < 0.05), lTh-FDG (r = -0.585, q < 0.05), and Bifidobacterium(r = -0.637, q < 0.05). Partial least squares structural equation modeling (PLS-SEM) revealed that Bifidobacterium had no direct effect on PSQI scores, but it influenced PSQI scores through the mediating effect of Thalamic-FDG. Conclusions: In AD patients with ID, there may be both a direct and an indirect association between Bifidobacterium and sleep quality, with thalamic glucose metabolism mediating the indirect association, indicating that treatments aimed at enhancing brain metabolism and probiotic supplementation may improve sleep quality in this population.

Keywords: Alzheimer's disease, Gut Microbiota, positron emission tomography, insomnia disorder, brainpathology

Received: 20 Jul 2025; Accepted: 29 Oct 2025.

Copyright: © 2025 Kang, Chen, Li, Zhao, Jing, Xie and Dong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Chunbo Dong, dcb101@sina.com

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