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Sci Rep. 2019 Mar 12;9(1):4191. doi: 10.1038/s41598-019-40544-3.

Cerebrospinal Fluid Spermidine, Glutamine and Putrescine Predict Postoperative Delirium Following Elective Orthopaedic Surgery.

Author information

1
Institute for Global Food Security, School of Biological Sciences, Queen's University Belfast, 8 Malone Road, Belfast, BT9 5BN, Northern Ireland.
2
Centre for Public Health, Queen's University Belfast, Block B, Institute of Clinical Sciences, Royal Victoria Hospital site, Grosvenor Road, Belfast, BT12 6BA, Northern Ireland. emma.cunningham@qub.ac.uk.
3
Centre for Public Health, Queen's University Belfast, Block B, Institute of Clinical Sciences, Royal Victoria Hospital site, Grosvenor Road, Belfast, BT12 6BA, Northern Ireland.
4
Centre for Experimental Medicine, Queen's University Belfast, Wellcome-Wolfson Institute for Experimental Medicine, 97 Lisburn Road, Belfast, BT9 7BL, Northern Ireland.
5
Outcomes Assessment Unit, Musgrave Park Hospital, Belfast Trust, Stockman's Lane, Belfast, BT9 7JB, Northern Ireland.
6
Cardiac Surgical Intensive Care Unit, Belfast Trust, Royal Victoria Hospital, Grosvenor Road, Belfast, BT12 6BA, Northern Ireland.
7
Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology, UK, Box 16, National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, UK.
8
UK Dementia Research Institute at UCL, Cruciform Building, Gower Street, London, London, WC1E 6BT, UK.
9
Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK, Box 16, National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, UK.
10
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, House V, S-431 80 Mölndal, Göteborg, Sweden.
11
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Blå Stråket 15, S-413 45, Gothenburg, Sweden.
12
Core Technology Unit for Mass Spectrometry, Faculty of Medicine, Health and Life Sciences, Queen's University Belfast, Belfast, UK.

Abstract

Delirium is a marker of brain vulnerability, associated with increasing age, pre-existing cognitive impairment and, recently, cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease. This nested case-control study used a targeted quantitative metabolomic methodology to profile the preoperative CSF of patients (n = 54) who developed delirium following arthroplasty (n = 28) and those who did not (n = 26). The aim was to identify novel preoperative markers of delirium, and to assess potential correlations with clinical data. Participants without a diagnosis of dementia (≥65 years) undergoing elective primary hip or knee arthroplasty were postoperatively assessed for delirium once-daily for three days. Groups were compared using multivariate, univariate and receiving operator characteristic (ROC) methods. Multivariate modelling using Orthogonal Partial Least Squares-Discriminant Analysis (OPLS-DA) of metabolomic data readily distinguished between delirium and control groups (R2 ≤ 0.56; Q2 ≤ 0.10). Three metabolites (spermidine, putrescine and glutamine) significantly differed between groups (P < 0.05; FDR < 0.07), and performed well as CSF biomarkers (ROC > 0.75). The biomarker performance of the two polyamines (spermidine/putrescine) was enhanced by ratio with CSF Aβ42 (ROC > 0.8), and spermidine significantly correlated with Aβ42 (pearson r = -0.32; P = 0.018). These findings suggest that spermidine and putrescine levels could be useful markers of postoperative delirium risk, particularly when combined with Aβ42, and this requires further investigation.

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