Emma L Cunningham, Bernadette McGuinness, Daniel F McAuley, Jamie Toombs, Tim Mawhinney, Seamus O'Brien, David Beverland, Jonathan M Schott, Michael P Lunn, Henrik Zetterberg, Anthony P Passmore
Annals of Surgery
doi: 10.1097/SLA.0000000000002684
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Objective
To test the hypothesis that APOE ε4 status and cerebrospinal fluid (CSF) Aβ42, T-tau and P-tau would independently predict the risk of postoperative delirium.

Background
Delirium following surgery is common and associated with adverse outcomes. Age and cognitive impairment are consistent risk factors for postoperative delirium.

Methods
This observational cohort study recruited 282 participants aged 65 years or older, without a diagnosis of dementia, admitted for primary elective hip or knee arthroplasty. Cognitive tests were undertaken preoperatively, blood and CSF were sampled at the time of spinal anesthesia, and participants were assessed daily postoperatively for delirium.

Results
Increasing age (P = 0.04), preoperative comorbidity (P = 0.03), type of surgery (P = 0.05), intravenous opioid usage (P = 0.04), and low CSF Aβ42 (P < 0.01) were independent predictors of postoperative delirium.

Conclusions
This study is the first to show an independent association between CSF Aβ42 and delirium incidence in an elective surgical population, suggesting that postoperative delirium may indicate incipient Alzheimer disease.

Xiaobei Pan, Emma L Cunningham, Anthony P Passmore, Bernadette McGuinness, Daniel F McAuley, David Beverland, Seamus O'Brien, Tim Mawhinney, Jonathan M Schott, Henrik Zetterberg, Brian D Green
Scientfic Reports
DOI: 10.1038/s41598-019-40544-3
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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.

Emma Louise Cunningham, Tim Mawhinney, David Beverland, Seamus O'Brien, Daniel F McAuley, Rebecca Cairns, Peter Passmore, Bernadette McGuinness
Age Ageing
DOI: 10.1093/ageing/afx042
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Introduction: delirium following surgery is common and is associated with negative outcomes. Preoperative cognitive impairment has been shown to be a risk factor for post-operative delirium. Often the cognitive tests used are cumbersome. This study tests the hypothesis that the quantification of brain vulnerability, using Apolipoprotein E (ApoE) status and neuropsychological tests, both traditional and more easily administered, can quantify the risk of post-operative delirium following elective primary arthroplasty surgery.

Keywords: Alzheimer's disease; cognition; delirium; executive dysfunction; older people; orthopaedic; post-operative cognitive dysfunction; post-operative delirium; subsyndromal; surgery.