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Exploring the causal relationship between delirium and sarcopenia using bidirectional two-sample Mendelian

Rui Zhou¹, Yumeng Fu¹, Peiling Wan¹

¹Department of Anesthesiology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China.

Progress in Neuro-Psychopharmacology & Biological Psychiatry

|March 13, 2025

Summary

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This study found a causal link between low hand-grip strength and delirium, suggesting sarcopenia may contribute to delirium development. However, medications did not appear to mediate this relationship.

Area of Science:

Gerontology
Genetics
Epidemiology

Background:

Population studies show associations between delirium and sarcopenia, but causality is unclear.
Understanding the causal links is crucial for effective prevention and treatment strategies.
Investigating the role of medication use in these conditions is also important.

Purpose of the Study:

To investigate the causal relationship between delirium and sarcopenia using Mendelian randomization.
To explore the causal effects of medication use on delirium and sarcopenia.
To clarify the potential mediating role of medications in the delirium-sarcopenia relationship.

Main Methods:

Bidirectional two-sample Mendelian randomization (MR) analysis using public genome-wide association studies (GWAS) data.

Keywords:

Appendicular lean mass Delirium GWAS Low hand-grip strength Mendelian randomization

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Inverse-variance weighted (IVW) method as the primary analysis, supported by weighted median and weighted mode.

Sensitivity analyses including Cochran's Q test, MR-Egger regression, MR-PRESSO, and leave-one-out methods were performed.

Main Results:

Genetically predicted low hand-grip strength showed a causal relationship with delirium (OR=1.31, P=0.032).
Diuretics and glucocorticoids were associated with appendicular lean mass; diabetes medications and immunosuppressants were associated with low hand-grip strength.
Sensitivity analyses confirmed the primary findings, despite evidence of heterogeneity and pleiotropy.

Conclusions:

Evidence suggests a causal link between low hand-grip strength (sarcopenia) and delirium.
Medication use did not appear to mediate the causal relationship between sarcopenia and delirium.
Further large-scale population studies are recommended to validate these findings.