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.
this study challenges the assertion that ApoE4 genotype predicts post-operative delirium. It replicates previous work suggesting cognitive impairment predicts post-operative delirium and shows for the 1st time that simple cognitive tests can be as effective as more detailed tests.
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.
Central alpha(1)-adrenoceptors are differentially regulated after chronic haloperidol and clozapine treatment. It is suggested that thalamic alpha(1)-adrenoceptors may represent a common anatomical locus contributing to the antipsychotic activity and/or alpha(1)-adrenoceptor centrally mediated side effects of both drugs, whereas the selective upregulation of cortical alpha(1)-adrenoceptor density by clozapine may contribute, in part, to its superior atypical properties.
BackgroundBetween 2012‐2014, an observational cohort study of postoperative delirium (POD) in an elective arthroplasty population recruited 315 individuals aged over 65, without a diagnosis of dementia. We are now conducting a follow‐up study to determine what effect POD has on cognition years later.MethodIn the baseline study, neuropsychological testing was undertaken preoperatively, cerebrospinal fluid (CSF) was sampled at the time of spinal anaesthesia and delirium was assessed daily on days 1‐3 postoperatively. Stored CSF (n = 270) was analysed for markers of inflammation and neurodegeneration. In 2020, all surviving participants were invited to take part in the follow‐up study.ResultThe average age of the cohort at baseline was 74.4 (5.8) years. Eight years later, 84% (n=264) of the observational study participants are still alive. Mortality rates in the intervening years are higher in those who developed POD (14/44, 32%) than those who did not (37/271, 14%), but is not statistically significant (p=0.13). Significant predictors of mortality in all participants included multi‐morbidity (p=0.007), age at surgery (p<0.001), performance on Colour Trails 2, a test of executive function(p<0.001); CSF glial fibrillary acidic protein (GFAP), a marker of inflammation (p=0.01); CSF neurofilament light (NFL), a marker of axonal degeneration (p=0.019); CSF interleukin‐8 (IL‐8), a marker of inflammation (p=0.007) and CSF triggering receptor expressed on myeloid cells 2 (sTREM2), a marker of age‐related neuroinflammation and tau‐related neurodegeneration (p=0.002).ConclusionThe majority of participants in this elective arthroplasty observational cohort are still alive eight years later. Older age at time of surgery, multimorbidity, lower neuropsychological performance and increased preoperative CSF measures of inflammation and neurodegeneration were associated with mortality in adults eight years following elective orthopaedic surgery.
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