Evidence mapPaperPMID 40922636Full record

ArticleBrain and behavior2025

The Relationship Between Human Cerebrospinal Fluid Proteins and the Risk of Delirium: A Study Based on Genetic Data.

Zhihui Xu, Fei Ye, Zhantang Yuan, Chiyi Liu, Simin Zhu, Binfei Li, Qibiao Wu

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Article in Brain and behavior, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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3 · Its place in the literature

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1 citing paper in PubMed.

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5 · Who and what money

Authors and funding

7 authors.

Zhihui XuFaculty of Chinese Medicine, Macau University of Science and Technology, Macau, China.ORCID https://orcid.org/0009-0000-3919-1527
Fei YeFaculty of Chinese Medicine, Macau University of Science and Technology, Macau, China.
Zhantang YuanDepartment of Emergency Medicine, Zhongshan Stomatological Hospital, Zhongshan City, Guangdong, China.
Chiyi LiuDepartment of Anesthesiology, Zhongshan People's Hospital, Zhongshan City, Guangdong, China.
Simin ZhuDepartment of Anesthesiology, Zhongshan People's Hospital, Zhongshan City, Guangdong, China.
Binfei LiFaculty of Chinese Medicine, Macau University of Science and Technology, Macau, China.
Qibiao WuFaculty of Chinese Medicine, Macau University of Science and Technology, Macau, China.

Funding

Chinese Medicine Guangdong Laboratory HQCML-C-2024006Science and Technology Development Fund, Macau SAR 0048/2023/AFJScience and Technology Development Fund, Macau SAR 0098/2021/A2
6 · The paper itself

Abstract

backgroundDelirium is an acute cognitive disturbance that is linked to increased healthcare costs, extended hospitalization, and a greater incidence of adverse outcomes, including cognitive decline. Despite its clinical importance, existing strategies for predicting and managing delirium remain inadequate. This study, therefore, sought to investigate the potential relationship between cerebrospinal fluid proteins and delirium via Mendelian randomization (MR) and to identify potential therapeutic targets.

methodsGenetic data related to delirium were obtained from the 11th iteration of the FinnGen Biobank, which includes a total of 431,880 individuals of Finnish ancestry consisting of 3827 cases and 428,053 controls. Data on 910 cerebrospinal fluid proteins from 970 samples were collected via the ONTIME platform (https://ontime.wustl.edu/hg38/). MR analysis was used to evaluate genetic associations between cerebrospinal fluid proteins and delirium. Additionally, enrichment analysis was performed on cerebrospinal fluid proteins with genetic associations to identify potential cellular pathways and therapeutic targets.

resultsWe identified 46 cerebrospinal fluid proteins associated with the occurrence of delirium. Among these, insulin (odds ratio [OR]: 1.35, 95% confidence interval [CI]: 1.07-1.70, p = 0.01), interleukin-7 (OR: 0.56, 95% CI: 0.37-0.85, p = 0.01), and B-cell lymphoma/leukemia 2-like protein 1 (OR: 0.63, 95% CI: 0.45-0.88, p = 0.01) were identified as key proteins. Horizontal pleiotropy had a minimal impact on establishing causal relationships, with p values of 0.08, 0.26, and 0.32, respectively. Additionally, no evidence of heterogeneity in genetic variation was found between these three cerebrospinal fluid proteins and delirium, with p values of 0.07, 0.45, and 0.96, respectively. Leave-one-out analysis further confirmed the stability and robustness of these associations. The enrichment analysis indicated that the cytokine-mediated signaling pathway plays a significant role in the pathogenesis of delirium.

conclusionOur study identified a genetic causal relationship between specific cerebrospinal fluid proteins and delirium, with insulin being a key factor. We also found that cytokine-mediated signaling pathways may contribute to the pathophysiology of delirium. Future research should focus on the roles of peripheral and central glucose metabolism, as well as cellular immunity, in the pathological processes of delirium.

Indexed as

Cerebrospinal Fluid ProteinsDeliriumAgedFemaleFinlandGenetic Predisposition to DiseaseHumansMaleMendelian Randomization AnalysisMiddle AgedCerebrospinal Fluid Proteinscerebrospinal fluid proteinscytokine signaling pathwaydeliriumMendelian randomization

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PMID40922636
PMCPMC12417801

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