Unraveling the role of polyamine metabolism in postoperative delirium: insights into biochemical mechanisms and biomarker potential
Postoperative delirium (POD) is a common complication in older surgical patients, linked to long-term cognitive decline and progression to dementia, yet its mechanisms remain unclear. We investigated arginine-related metabolites (ARMs) in cerebrospinal fluid (CSF) from 248 patients undergoing elective-surgery: 25 developed POD. Targeted mass spectrometry, gene expression profiling, and machine learning were applied to identify metabolic predictors. POD patients showed significant correlations with citrulline, ornithine, and glutamine, while models highlighted glutamine, glutamic acid, putrescine, N1-acetylspermidine, and spermidine as key biomarkers, achieving >77% predictive accuracy. Cluster and pathway analyses revealed POD-specific shifts in GABA synthesis and polyamine metabolism, contrasting with urea cycle dominance in non-POD cases. Associations persisted after adjusting for age and CSF Aβ42. Preoperative profiles in polyamine metabolism, ammonia detoxification, and neurotransmitter regulation suggest underlying neuroinflammatory and oxidative stress vulnerabilities that reduce resilience. Targeting polyamine biosynthesis may offer novel preventative and therapeutic strategies to mitigate POD and dementia risk.
Authors
- Brian D. Green (ORCID: https://orcid.org/0000-0003-3331-0032)
- Miroslava Čuperlović‐Culf (ORCID: https://orcid.org/0000-0002-9483-8159)
- Jyothi Dhuguru
- Xiaobei Pan (ORCID: https://orcid.org/0000-0002-6526-1338)
- Vaibhav Kumar Pandya (ORCID: https://orcid.org/0000-0002-8500-9009)
- Marie E. Migaud (ORCID: https://orcid.org/0000-0002-9626-2405)
- Shiva Kant
- Anthony Peter Passmore
- Henrik Zetterberg
- Leiv Otto Watne
- Emma L. Cunningham
- Bernadette McGuinness
- Nadia Ashrafi
- Stewart F. Graham
- Nazia Saiyed
Institutions
- Queen's University Belfast (GB)
- University of Wisconsin–Madison (US)
- University of Ulster (GB)
- Oakland University (US)
- University of Oslo (NO)
- Beaumont Health (US)
- Akershus University Hospital (NO)
- Sahlgrenska University Hospital (SE)
- USA Mitchell Cancer Institute (US)
- Research Complex at Harwell (GB)
- UK Dementia Research Institute (GB)
- Sugen Life Sciences (India) (IN)
- Beaumont Hospital, Royal Oak (US)
- Royal Victoria Hospital (GB)
- Royal Oak Community Coalition (US)
- National Research Council Canada (CA)
- Beaumont Hospital, Troy (US)
- University College London (GB)
- Indian Institute of Science Bangalore (IN)
- University of Gothenburg (SE)
- Auburn University at Montgomery (US)
Publication Details
- Journal
- npj Aging
- Published
- 2026-02-21
- DOI
- https://doi.org/10.1038/s41514-025-00324-y
- Primary Topic
- Intensive Care Unit Cognitive Disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Institute for Health and Care Research
- University College London
- European Commission
- Vetenskapsrådet
- Nasjonalforeningen for Folkehelsen
- UK Dementia Research Institute
- National Institutes of Health
- HORIZON EUROPE Framework Programme
- National Institute on Aging