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Association of insulin resistance with delirium and CSF biomarkers of Alzheimer’s disease in elderly patients with hip fracture

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Abstract

Background

Delirium is associated with dementia, which shares symptoms of cognitive dysfunctions. Notably, pathological mechanisms of Alzheimer's disease (AD) appear involved in both conditions. Insulin resistance has been reported to be a risk factor for AD, leading to neurodegeneration and cognitive impairment by affecting amyloid-beta (Aβ) metabolism, tau phosphorylation, and neuro-inflammation. Thus, insulin resistance may provide pathophysiological clues to the occurrence of delirium.

Aim

To investigate the relationship between preoperative insulin resistance, insulin concentrations in the cerebrospinal fluid (CSF), and delirium in elderly patients with hip fracture.

Methods

The study included 138 elderly patients with or without pre-existing dementia who underwent hip fracture surgery. Delirium was diagnosed with the confusion assessment method performed daily from pre-operation to 5 days post-operation. CSF and blood samples were collected at the beginning of spinal anesthesia. The concentrations of insulin, amyloid-beta1-42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau)181 were determined by ELISA. Homeostasis model assessment (HOMA-IR) was used to assess insulin resistance.

Results

Sixty-one (44%) of 138 hip fracture patients developed delirium peri-operatively. Compared to non-delirium group, the preoperative HOMA-IR index in delirium was much higher (median 3.3 vs 2.8, p = 0.001), but the CSF insulin concentration was significantly decreased (median 1.5 vs 2.2 mU/L, p < 0.001). Binary logistic regression analysis showed that HOMA-IR index and CSF insulin concentration were independent risk factors for delirium (p < 0.05). HOMA-IR index was negatively correlated with CSF insulin concentrations (rho =  − 0.55, p < 0.001). Multiple linear regression analysis showed that AD core biomarkers were significantly correlated with HOMA-IR index and CSF insulin level (p < 0.05).

Conclusion

This study innovatively examined insulin concentrations in serum and cerebrospinal fluid in patients with delirium. Our findings suggest that preoperative insulin resistance may affect the occurrence of delirium. The potential association between insulin resistance and delirium may be related to insulin resistance affecting the metabolism of AD biomarkers.

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Data Availability Statement

The data have not been previously presented orally or by poster at scientific meetings.

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Acknowledgements

Foremost, we would like to thank all the patients included in this study. We would like to thank the staff at the Department of Orthopedic Surgery, Department of Anesthesiology, Department of Internal Medicine, as well as Department of Neurology. We would also like to thank the Department of Liver Disease for the help in the storage of specimens

Funding

The study was funded by the Provincial Science and Technology Program of Hebei Province (No. 22377732D).

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Authors and Affiliations

  1. Department of Anesthesiology, The Third Hospital of Hebei Medical University, No. 139 Ziqiang Road, Shijiazhuang, 050051, China

    Jie Wang, Pengzhan Shuang, Zhao Li, Longbiao Zhao, Xiuli Wang & Peng Liu

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  1. Jie Wang
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  2. Pengzhan Shuang
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  3. Zhao Li
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Contributions

LP and WJ contributed to the study concept and design, data acquisition, data analysis and interpretation, and drafting and revising the manuscript. LZ and ZLB contributed in the data acquisition, study coordination, data interpretation, and revising of the manuscript. SPZ contributed in the data acquisition, data interpretation, and revising of the manuscript. WXL contributed to the study concept and design, data analysis and interpretation, and revising of the manuscript. All the authors have read and approved the final manuscript.

Corresponding author

Correspondence to Peng Liu.

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Conflict of interest

The authors report no conflicts with any product mentioned or concept discussed in this article.

Statement of human and animal rights

The study was conducted in accordance with the Declaration of Helsinki. The ethics committee of the Third Hospital of Hebei Medical University approved the study (Ethics Committee No.: Department 2021-063-1).

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Informed consent was obtained from the patients and their closest relative.

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Wang, J., Shuang, P., Li, Z. et al. Association of insulin resistance with delirium and CSF biomarkers of Alzheimer’s disease in elderly patients with hip fracture. Aging Clin Exp Res 35, 1521–1529 (2023). https://doi.org/10.1007/s40520-023-02429-4

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