Age-Related Perioperative Neurocognitive Disorders: Experimental Models and Druggable Targets.

With the worldwide increase in life span, surgical patients are becoming older and have a greater propensity for postoperative cognitive impairment, either new onset or through deterioration of an existing condition; in both conditions, knowledge of the patient's preoperative cognitive function and postoperative cognitive trajectory is imperative. We describe the clinical utility of a tablet-based technique for rapid assessment of the memory and attentiveness domains required for executive function. The pathogenic mechanisms for perioperative neurocognitive disorders have been investigated in animal models in which excessive and/or prolonged postoperative neuroinflammation has emerged as a likely contender. The cellular and molecular species involved in postoperative neuroinflammation are the putative targets for future therapeutic interventions that are efficacious and do not interfere with the surgical patient's healing process.

An exploratory research report on brain mineralization in postoperative delirium and cognitive decline.

Delirium is a severe postoperative complication associated with poor overall and especially neurocognitive prognosis. Altered brain mineralization is found in neurodegenerative disorders but has not been studied in postoperative delirium and postoperative cognitive decline. We hypothesized that mineralization-related hypointensity in susceptibility-weighted magnetic resonance imaging (SWI) is associated with postoperative delirium and cognitive decline. In an exploratory, hypothesis-generating study, we analysed a subsample of cognitively healthy patients ≥65 years who underwent SWI before (N = 65) and 3 months after surgery (N = 33). We measured relative SWI intensities in the basal ganglia, hippocampus and posterior basal forebrain cholinergic system (pBFCS). A post hoc analysis of two pBFCS subregions (Ch4, Ch4p) was conducted. Patients were screened for delirium until the seventh postoperative day. Cognitive testing was performed before and 3 months after surgery. Fourteen patients developed delirium. After adjustment for age, sex, preoperative cognition and region volume, only pBFCS hypointensity was associated with delirium (regression coefficient [90% CI]: B = -15.3 [-31.6; -0.8]). After adjustments for surgery duration, age, sex and region volume, perioperative change in relative SWI intensities of the pBFCS was associated with cognitive decline 3 months after surgery at a trend level (B = 6.8 [-0.9; 14.1]), which was probably driven by a stronger association in subregion Ch4p (B = 9.3 [2.3; 16.2]). Brain mineralization, particularly in the cerebral cholinergic system, could be a pathomechanism in postoperative delirium and cognitive decline. Evidence from our studies is limited because of the small sample and a SWI dataset unfit for iron quantification, and the analyses presented here should be considered exploratory.

Treatment of Delirium During Critical Illness.

Delirium, an acute disturbance in mental status due to another medical condition, is common and morbid in the intensive care unit. Despite its clear association with multiple common risk factors and important outcomes, including mortality and long-term cognitive impairment, both the ultimate causes of and ideal treatments for delirium remain unclear. Studies suggest that neuroinflammation, hypoxia, alterations in energy metabolism, and imbalances in multiple neurotransmitter pathways contribute to delirium, but commonly used treatments (e.g., antipsychotic medications) target only one or a few of these potential mechanisms and are not supported by evidence of efficacy. At this time, the optimal treatment for delirium during critical illness remains avoidance of risk factors, though ongoing trials may expand on the promise shown by agents such as melatonin and dexmedetomidine.

Risk factors and associated outcomes of postoperative delirium after open abdominal aortic aneurysm repair.

OBJECTIVE: Open abdominal aortic aneurysm repair (OAR) is a major vascular procedure that incurs a large physiologic demand, increasing the risk for complications such as postoperative delirium (POD). We sought to characterize POD incidence, identify delirium risk factors, and evaluate the effect of delirium on postoperative outcomes. We hypothesized that POD following OAR would be associated with increased postoperative complications and resource utilization. METHODS: This was a retrospective study of all OAR cases from 2012 to 2020 at a single tertiary care center. POD was identified via a validated chart review method based on key words and Confusion Assessment Method assessments. The primary outcome was POD, and secondary outcomes included length of stay, non-home discharge, 90-day mortality, and 1-year survival. Bivariate analysis as appropriate to the data was used to assess the association of delirium with postoperative outcomes. Multivariable binary logistic regression was used to identify risk factors for POD and Cox regression for variables associated with worse 1-year survival. RESULTS: Overall, 198 OAR cases were included, and POD developed in 34% (n = 67). Factors associated with POD included older age (74 vs 69 years; P < .01), frailty (50% vs 28%; P < .01), preoperative dementia (100% vs 32%; P < .01), symptomatic presentation (47% vs 27%; P < .01), preoperative coronary artery disease (44% vs 28%; P = .02), end-stage renal disease (89% vs 32%; P < .01) and Charlson Comorbidity Index score >4 (42% vs 26%; P = .01). POD was associated with 90-day mortality (19% vs 5%; P < .01), non-home discharge (61% vs 30%; P < .01), longer median hospital length of stay (14 vs 8 days; P < .01), longer median intensive care unit length of stay (6 vs 3 days; P < .01), postoperative myocardial infarction (7% vs 2%; P = .045), and postoperative pneumonia (19% vs 8%; P = .01). On multivariable analysis, risk factors for POD included older age, history of end-stage renal disease, lack of epidural, frailty, and symptomatic presentation. A Cox proportional hazards model revealed that POD was associated with worse survival at 1 year (hazard ratio, 3.8; 95% confidence interval, 1.6-9.0; P = .003). CONCLUSIONS: POD is associated with worse postoperative outcomes and increased resource utilization. Future studies should examine the role of improved screening, implementation of delirium prevention bundles, and multidisciplinary care for the most vulnerable patients undergoing OAR.

A Toolkit for Delirium Identification and Promoting Partnerships Between Carers and Nurses: A Pilot Pre-Post Feasibility Study.

BACKGROUND: Delirium is frightening for people experiencing it and their carers, and it is the most common hospital-acquired complication worldwide. Delirium is associated with higher rates of morbidity, mortality, residential care home admission, dementia, and carer stress and burden, yet strategies to embed the prevention and management of delirium as part of standard hospital care remain challenging. Carers are well placed to recognize subtle changes indicative of delirium, and partner with nurses in the prevention and management of delirium. OBJECTIVE: To evaluate a Prevention & Early Delirium Identification Carer Toolkit (PREDICT), to support partnerships between carers and nurses to prevent and manage delirium. DESIGN: A pre-post-test intervention and observation study. MAIN MEASURES: Changes in carer knowledge of delirium; beliefs about their role in partnering with nurses and intended and actual use of PREDICT; carer burden and psychological distress. Secondary measures were rates of delirium. PARTICIPANTS: Participants were carers of Indigenous patients aged 45 years and older and non-Indigenous patients aged 65 years and older. INTERVENTION: Nurses implemented PREDICT, with a view to provide carers with information about delirium and strategies to address caregiving stress and burden. KEY RESULTS: Participants included 25 carers (43% response rate) (n = 17, 68% female) aged 29-88 (M = 65, SD = 17.7 years). Carer delirium knowledge increased significantly from pre-to-post intervention (p = < .001; CI 2.07-4.73). Carers' intent and actual use of PREDICT was (n = 18, 72%; and n = 17, 68%). Carer burden and psychological distress did not significantly change. The incidence of delirium in the intervention ward although not significant, decreased, indicating opportunity for scaling up. CONCLUSION: The prevention and management of delirium are imperative for safe and quality care for patients, carers, and staff. Further comprehensive and in-depth research is required to better understand underlying mechanisms of change and explore facets of nursing practice influenced by this innovative approach.

Fish oil omega-3 Fatty Acids Alleviate Postoperative delirium-like Behavior in aged mice by Attenuating Neuroinflammation and Oxidative Stress.

Postoperative delirium (POD) is a common and serious neuropsychiatric syndrome among older patients, and lacks effective therapies. Omega-3 fatty acids, possessing anti-inflammatory and antioxidant properties, have shown potent neuroprotective effects in several diseases. The present study investigated whether omega-3 fatty acids could exert a neuroprotective role against POD in aged mice. A mouse model of POD was established to explore the role of omega-3 fatty acids in laparotomy-induced delirium-like behavior by evaluating systemic inflammatory changes, neuroinflammation, oxidative stress, and behavior at different time points in aged mice. Oral gavage with omega-3 fatty acids (300 mg/kg) for 3 weeks before surgery significantly attenuated anesthesia/surgery-induced POD-like behavior and the accumulation of proinflammatory cytokines from the peripheral blood in aged mice. Moreover, it also remarkably mitigated neuroinflammation and the oxidative stress response (malondialdehyde [MDA] and superoxide dismutase [SOD]) in the prefrontal cortex and hippocampus of surgical mice. Our findings provided evidence that pretreatment with omega-3 fatty acids may play a vital role in the treatment of POD through mechanisms involving its anti-inflammatory and antioxidant effects, which may be a promising prevention strategy for POD in aged patients.

Late-onset delirious mania: Does it ring a bell?

BACKGROUND: Bell's mania was first described in 1849, and other terms have been used to describe this condition, including delirious mania, mania with delirium, and excited delirium. However, no international diagnostic manual has included mania as an independent diagnostic tool. The criteria for delirious mania were proposed by Bond et al. METHODS: We present a case of a man without a personal or family psychiatric history who experienced his first manic episode of delirium and psychosis at 76 years old. CONCLUSIONS: The case described in this study is compatible with mood disorders, the original description of Bell's mania, and Bond's definition of delirious mania. Although rare, extremely late-onset primary mania can occur without personal or family psychiatric history. The initial clinical presentation of delirium requires a thorough medical investigation, including magnetic resonance imaging (MRI) and lumbar puncture with neuronal antibodies. The addition of delirious mania to the group of bipolar disorders in future editions of The International Classification of Diseases (ICD) and Diagnostic and Statistical Manual of Mental Disorders (DSM) has therapeutic and prognostic implications. The Bond criteria can provide valuable information in this respect. Further investigations are necessary to clarify the pathophysiology and epidemiology of delirious mania.

Association between perioperative self-reported sleep disturbances and delirium risk in elderly patients following total joint arthroplasty: a cohort study.

Perioperative sleep disturbance may increase delirium risk. However, the role of perioperative sleep disturbance in delirium following total joint arthroplasty remains unclear. This prospective cohort study aimed to observe the delirium risk in patients with sleep disturbances. After excluding pre-existing sleep disturbances, older patients scheduled for total joint arthroplasty from July 17, 2022, to January 12, 2023, were recruited. Preoperative sleep disturbance or postoperative sleep disturbance was defined as a Chinese version of the Richards-Campbell Sleep Questionnaire (RCSQ) score of <50 during hospitalisation. A cut-off score of 25 was used to classify the severity of sleep disturbance. The primary outcome was the incidence of postoperative delirium. In all, 11.6% of cohort patients (34/294) developed delirium. After multivariate analysis, a preoperative Day 1 RCSQ score of ≤25 (odds ratio [OR] 3.62, 95% confidence interval [CI] 1.19-10.92; p = 0.02), occurrence of sleep disturbances (OR 2.76, 95% CI 1.19-6.38; p = 0.02) and RCSQ score of ≤25(OR 2.91, 95% CI 1.33-6.37; p = 0.007) postoperatively were strong independent predictors of delirium. After sensitivity analysis for daily delirium, a postoperative Day 1 RCSQ score of ≤25 (OR 9.27, 95% CI 2.72-36.15; p < 0.001) was associated with a greater risk of delirium on postoperative Day 1, with a reasonable discriminative area under the curve of 0.730. We concluded that postoperative but not preoperative sleep disturbances may be an independent factor for delirium risk. Sleep disturbance on the first night after surgery was a good predictor of subsequent delirium, no matter the nature of self-reported sleep disturbance.

Preoperative Delirium Risk Screening in Patients Undergoing a Cardiac Surgery: Results from the Prospective Observational FINDERI Study.

OBJECTIVE: Postoperative delirium (POD) is a common complication of cardiac surgery that is associated with higher morbidity, longer hospital stay, cognitive decline, and mortality. Preoperative assessments may help to identify patients´ POD risk. However, a standardized screening assessment for POD risk has not been established. DESIGN: Prospective observational FINd DElirium RIsk factors (FINDERI) study. PARTICIPANTS: Patients aged ≥50 years undergoing cardiac surgery. MEASUREMENTS: The primary aim was to analyze the predictive value of the Delirium Risk Screening Questionnaire (DRSQ) prior to cardiac surgery. Secondary aims are to investigate cognitive, frailty, and geriatric assessments, and to use data-driven machine learning (ML) in predicting POD. Predictive properties were assessed using receiver operating characteristics analysis and multivariate approaches (regularized LASSO regression and decision trees). RESULTS: We analyzed a data set of 504 patients (68.3 ± 8.2 years, 21.4% women) who underwent cardiac surgery. The incidence of POD was 21%. The preoperatively administered DRSQ showed an area under the curve (AUC) of 0.68 (95% CI 0.62, 0.73), and the predictive OR was 1.25 (95% CI 1.15, 1.35, p <0.001). Using a ML approach, a three-rule decision tree prediction model including DRSQ (score>7), Trail Making Test B (time>118), and Montreal Cognitive Assessment (score ≤ 22) was identified. The AUC of the three-rule decision tree on the training set was 0.69 (95% CI 0.63, 0.75) and 0.62 (95% CI 0.51, 0.73) on the validation set. CONCLUSION: Both the DRSQ and the three-rule decision tree might be helpful in predicting POD risk before cardiac surgery.

The Association of Plasma Leptin, Soluble Leptin Receptor and Total and High-Molecular Weight Adiponectin With the Risk of Perioperative Neurocognitive Disorders.

BACKGROUND: Perioperative neurocognitive disorders (NCD) are poorly characterized in terms of their risk factor profiles. Leptin and adiponectin are adipose-tissue-derived hormones with a role in inflammation and atherosclerosis whose function in perioperative NCD is unclear. Here, we used a cohort of older adults to examine the association of preoperative plasma concentrations of these biomarkers with the risk of perioperative NCD. METHODS: Prospective analysis of 768 participants aged ≥ 65 years of the BioCog study. Blood was collected before surgery for measurement of plasma total and high-molecular-weight (hmw) adiponectin, leptin, and soluble leptin receptor (sOB-R). The free leptin index (FLI, leptin:sOB-R) was calculated. Postoperative delirium (POD) was assessed twice daily until postoperative day 7/discharge. Five hundred twenty-six patients (68.5%) returned for 3-month follow-up and provided data on postoperative cognitive dysfunction (POCD). POCD was defined as a decline on six neuropsychological tests that exceeded that of a nonsurgical control group. Logistic regression analyses examined the associations of each exposure with POD and POCD risk, in separate models adjusted for age, sex, fasting, surgery type, and body mass index (BMI). RESULTS: Of 768 patients, 152 (19.8%) developed POD. Of 526 attendants of the follow-up, 54 (10.3%) had developed POCD. Leptin, sOB-R, and total and hmw adiponectin were each not associated with POD. For POCD, we observed reduced risk in patients in FLI quartile 4 compared with quartile 1 (odds ratio, 0.26; 95% CI 0.08, 0.89). Sensitivity analyses for the outcome POD revealed statistically significant interaction terms of sOB-R and total adiponectin with obesity (BMI≥30kg/m2 versus BMI<30kg/m2). For the outcome POCD, a higher sOB-R was associated with an increased risk in the obese subgroup (odds ratio, 4.00; 95% CI 1.01, 15.86). CONCLUSIONS: We did not find consistent evidence for the role of leptin, its receptor, and total and hmw adiponectin in POD and POCD risk. Future research should be used to support or refute our findings and to fully characterize any differences in the associations of these hormones with POD/POCD between obese and nonobese individuals.

A joint frailty model for recurrent and competing terminal events: Application to delirium in the ICU.

Joint models linking longitudinal biomarkers or recurrent event processes with a terminal event, for example, mortality, have been studied extensively. Motivated by studies of recurrent delirium events in patients receiving care in an intensive care unit (ICU), we devise a joint model for a recurrent event process and multiple terminal events. Being discharged alive from the ICU or experiencing mortality may be associated with a patient's hazard of delirium, violating the assumption of independent censoring. Moreover, the direction of the association between the hazards of delirium and mortality may be opposite of the direction of association between the hazards of delirium and ICU discharge. Hence treating either terminal event as independent censoring may bias inferences. We propose a competing joint model that uses a latent frailty to link a patient's recurrent and competing terminal event processes. We fit our model to data from a completed placebo-controlled clinical trial, which studied whether Haloperidol could prevent death and delirium among ICU patients. The clinical trial served as a foundation for a simulation study, in which we evaluate the properties, for example, bias and confidence interval coverage, of the competing joint model. As part of the simulation study, we demonstrate the shortcomings of using a joint model with a recurrent delirium process and a single terminal event to study delirium in the ICU. Lastly, we discuss limitations and possible extensions for the competing joint model. The competing joint model has been added to frailtypack, an R package for fitting an assortment of joint models.

The risk of delirium after sedation with propofol or midazolam in intensive care unit patients.

AIM: Knowledge of risk factors may provide strategies to reduce the high burden of delirium in intensive care unit (ICU) patients. We aimed to compare the risk of delirium after deep sedation with propofol versus midazolam in ICU patients. METHODS: In this prospective cohort study, ICU patients who were in an unarousable state for ≥24 h due to continuous sedation with propofol and/or midazolam were included. Patients admitted ≤24 h, those with an acute neurological disorder and those receiving palliative sedation were excluded. ICU patients were assessed daily for delirium during the 7 days following an unarousable state due to continuous sedation. RESULTS: Among 950 included patients, 605 (64%) subjects were delirious during the 7 days after awaking. The proportion of subsequent delirium was higher after midazolam sedation (152/207 [73%] patients) and after both propofol and midazolam sedation (257/377 [68%] patients), compared to propofol sedation only (196/366 [54%] patients). Midazolam sedation (adjusted cause-specific hazard ratio [adj. cause-specific HR] 1.32, 95% confidence interval [CI] 1.05-1.66) and propofol and midazolam sedation (adj. cause-specific HR 1.29, 95% CI 1.06-1.56) were associated with a higher risk of subsequent delirium compared to propofol sedation only. CONCLUSION: This study among sedated ICU patients suggests that, compared to propofol sedation, midazolam sedation is associated with a higher risk of subsequent delirium. This risk seems more apparent in patients with high cumulative midazolam intravenous doses. Our findings underpin the recommendations of the Society of Critical Care Medicine Pain, Agitation/sedation, Delirium, Immobility (rehabilitation/mobilization), and Sleep (disruption) guidelines to use propofol over benzodiazepines for sedation in ICU patients.

A Mediation Analysis Examining High Risk, Anticholinergic Medication Use, Delirium, and Dementia After Major Surgery.

INTRODUCTION: Anticholinergic medications are known to cause adverse cognitive effects in community-dwelling older adults and medical inpatients, including dementia. The prevalence with which such medications are prescribed in older adults undergoing major surgery is not well described nor is their mediating relationship with delirium and dementia. We sought to determine the prevalence of high-risk medication use in major surgery patients and their relationship with the subsequent development of dementia. METHODS: This was a retrospective cohort study which used data between January 2013 and December 2019, in a large midwestern health system, including sixteen hospitals. All patients over age 50 undergoing surgery requiring an inpatient stay were included. The primary exposure was the number of doses of anticholinergic medications delivered during the hospital stay. The primary outcome was a new diagnosis of Alzheimer's disease and related dementias at 1-y postsurgery. Regression methods and a mediation analysis were used to explore relationships between anticholinergic medication usage, delirium, and dementia. RESULTS: There were 39,665 patients included, with a median age of 66. Most patients were exposed to anticholinergic medications (35,957/39,665; 91%), and 7588/39,665 (19.1%) patients received six or more doses during their hospital stay. Patients with at least six doses of these medications were more likely to be female, black, and with a lower American Society of Anesthesiologists class. Upon adjusted analysis, high doses of anticholinergic medications were associated with increased odds of dementia at 1 y relative to those with no exposure (odds ratio 2.7; 95% confidence interval 2.2-3.3). On mediation analysis, postoperative delirium mediated the effect of anticholinergic medications on dementia, explaining an estimated 57.6% of their association. CONCLUSIONS: High doses of anticholinergic medications are common in major surgery patients and, in part via a mediating relationship with postoperative delirium, are associated with the development of dementia 1 y following surgery. Strategies to decrease the use of these medications and encourage the use of alternatives may improve long-term cognitive recovery.

Drugs, Delirium, and Trauma: Substance Use and Incidence of Delirium After Traumatic Brain Injury.

INTRODUCTION: There is a paucity of data on the effect of preinjury substance (alcohol, drugs) abuse on the risk of delirium in patients with traumatic brain injury (TBI). This study aimed to assess the incidence of delirium among patients with blunt TBI in association with different substances. METHODS: We analyzed the 2020 American College of Surgeons-Trauma Quality Improvement Program. We included all adult (≥18 y) patients with blunt TBI who had a recorded substance (drugs and alcohol) screening. Our primary outcome was the incidence of delirium. RESULTS: A total of 72,901 blunt TBI patients were identified. The mean (standard deviation) age was 56 (20) years and 68.0% were males. The median (interquartile range) injury severity score was 17 (10-25). Among the study population, 23.1% tested positive for drugs (Stimulants: 3.0%; Depressants: 2.9%, hallucinogens: 5.1%, Cannabinoids: 13.4%, TCAs: 0.1%), and 22.8% tested positive for Alcohol. Overall, 1856 (2.5%) experienced delirium. On univariate analysis, patients who developed delirium were more likely to have positive drug screening results. On multivariable regression analyses, positive screen tests for isolated stimulants (adjusted odds ratio [aOR]: 1.340, P = 0.018), tricyclic antidepressants (aOR: 3.107, P = 0.019), and cannabinoids (aOR: 1.326, P ≤ 0.001) were independently associated with higher odds of developing delirium. CONCLUSIONS: Nearly one-fourth of adult patients with blunt TBI had an initial positive substance screening test. Patients with positive results for isolated stimulants, tricyclic antidepressants, and cannabinoids were at a higher risk of developing delirium, whereas this association was not evident with other drugs and alcohol-positive tests. These findings emphasize the need for early drug screening in TBI patients and close monitoring of patients with positive screening tests.

A pragmatic tool to screen for pre-transplant cognitive impairment among potential candidates for liver transplant.

INTRODUCTION: Cognitive impairment (CI) among liver transplant (LT) candidates is associated with increased risk of waitlist mortality and inferior outcomes. While formal neurocognitive evaluation is the gold standard for CI diagnosis, the Montreal Cognitive Assessment (MoCA) is often used for first-line cognitive screening. However, MoCA requires specialized training and may be too lengthy for a busy evaluation appointment. An alternate approach may be the Quick Dementia Rating System (QDRS), which is patient- and informant-based and can be administered quickly. We compared potential LT candidates identified by MoCA and QDRS as potentially benefiting from further formal cognitive evaluation. METHODS: We identified 46 potential LT candidates enrolled at a single center of a prospective, observational cohort study who were administered MoCA and QDRS during transplant evaluation (12/2021-12/2022). Scores were dichotomized as (1) normal versus abnormal and (2) normal/mild impairment versus more-than-mild impairment. We calculated sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of QDRS compared to MoCA. RESULTS: By MoCA, this population had a prevalence of 48% normal cognition, 48% mild, 4% moderate, and 0% severe impairment. This was categorized as 96% normal/mild and 4% more-than-mild impairment. When comparing to MoCA cognitive screening, QDRS had a sensitivity of 61%, specificity of 56%, NPV of 56%, and PPV of 61%. When identifying more-than-mild impairment, QDRS had a sensitivity of 100%, specificity of 73%, NPV of 100%, and PPV of 10%. CONCLUSION: The high sensitivity and NPV of QDRS in identifying more-than-mild impairment suggests it could identify potential LT candidates who would benefit from further formal cognitive evaluation. The ability to administer QDRS quickly and remotely makes it a pragmatic option for pre-transplant screening.

Preoperative cognitive function as a risk factor of postoperative delirium in cancer surgeries: A systematic review and meta-analysis.

Postoperative delirium (POD) after cancer surgeries can be a result of chemo brain, anesthesia, surgery duration, and preoperative cognitive impairment. Although older age and preoperative cognitive dysfunction were reported to increase the risk of POD in noncardiac surgery, the role of preoperative cognitive function and age in the development of POD after all types of cancer surgeries is not clear. This study aimed to determine the relationship between preoperative cognitive function and likelihood of POD after cancer surgeries. This study used three main online databases and followed PRISMA guidelines. English language original articles that examined preoperative cognitive function before solid tumor cancer surgery and assessed patients for postoperative delirium were included. We employed the random effect meta-analysis method. The overall incidence of POD ranged from 8.7% to 50.9%. The confusion assessment method was the most common tool used to assess delirium. Mini-mental state evaluation (MMSE), Mini-cog, and Montreal cognitive assessment were the most common tools to assess cognitive function. The pooled (total observation = 4676) random effects SMD was estimated at -0.84 (95% confidence interval [CI]: -1.30 to -0.31), indicating that lower MMSE scores before surgery are associated with a higher risk of POD. The pooled (total observation = 2668) random effects OR was estimated at 5.17 (95% CI: 2.51 to -10.63), indicating preoperative cognitive dysfunction can significantly predict the occurrence of POD after cancer surgeries. In conclusion, preoperative cognitive function is an independent and significant predictor of POD after solid tumor cancer surgeries.

Butyrylcholinesterase activity in patients with postoperative delirium after cardiothoracic surgery or percutaneous valve replacement- an observational interdisciplinary cohort study.

BACKGROUND AND OBJECTIVES: Postoperative delirium is a frequent and severe complication after cardiac surgery. Activity of butyrylcholinesterase (BChE) has been discussed controversially regarding a possible role in its development. This study aimed to investigate the relevance of BChE activity as a biomarker for postoperative delirium after cardiac surgery or percutaneous valve replacement. METHODS: A total of 237 patients who received elective cardiothoracic surgery or percutaneous valve replacement at a tertiary care centre were admitted preoperatively. These patients were tested with the Montreal Cognitive Assessment investigating cognitive deficits, and assessed for postoperative delirium twice daily for three days via the 3D-CAM or the CAM-ICU, depending on their level of consciousness. BChE activity was measured at three defined time points before and after surgery. RESULTS: Postoperative delirium occurred in 39.7% of patients (n = 94). Univariate analysis showed an association of pre- and postoperative BChE activity with its occurrence (p = 0.037, p = 0.001). There was no association of postoperative delirium and the decline in BChE activity (pre- to postoperative, p = 0.327). Multivariable analysis including either preoperative or postoperative BChE activity as well as age, MoCA, type 2 diabetes mellitus, coronary heart disease, type of surgery and intraoperative administration of red-cell concentrates was performed. Neither preoperative nor postoperative BChE activity was independently associated with the occurrence of postoperative delirium (p = 0.086, p = 0.484). Preoperative BChE activity was lower in older patients (B = -12.38 (95% CI: -21.94 to -2.83), p = 0.011), and in those with a history of stroke (B = -516.173 (95% CI: -893.927 to -138.420), p = 0.008) or alcohol abuse (B = -451.47 (95% CI: -868.38 to -34.55), p = 0.034). Lower postoperative BChE activity was independently associated with longer procedures (B = -461.90 (95% CI: -166.34 to -757.46), p = 0.002), use of cardiopulmonary bypass (B = -262.04 (95% CI: -485.68 to -38.39), p = 0.022), the number of administered red cell-concentrates (B = -40.99 (95% CI: -67.86 to -14.12), p = 0.003) and older age (B = -9.35 (95% CI: -16.04 to -2.66), p = 0.006). CONCLUSION: BChE activity is not independently associated with the occurrence of postoperative delirium. Preoperative BChE values are related to patients' morbidity and vulnerability, while postoperative activities reflect the severity, length and complications of surgery.

Does the Etiology, Phenomenology and Motor Subtype of Delirium Differ When It Occurs in Patients With An Underlying Dementia?: A Multi-Site, International Study.

OBJECTIVES: To compare the etiology, phenomenology and motor subtype of delirium in patients with and without an underlying dementia. METHODS: A combined dataset (n = 992) was collated from two databases of older adults (>65 years) from liaison psychiatry and palliative care populations in Ireland and India. Phenomenology and severity of delirium were analysed using the Delirium Symptom Rating Scale Revised (DRS-R98) and contributory etiologies for the delirium groups were ascertained using the Delirium Etiology Checklist (DEC). Delirium motor subtype was documented using the abbreviated version of the Delirium Motor Subtype Scale (DMSS4). RESULTS: Delirium superimposed on dementia (DSD) showed greater impairment in short term memory, long term memory and visuospatial ability than the delirium group but showed significantly less perceptual disturbance, temporal onset and fluctuation. Systemic infection, cerebrovascular and other Central nervous system etiology were associated with DSD while metabolic disturbance, organ insufficiency and intracranial neoplasm were associated with the delirium only group. CONCLUSION: The etiology and phenomenology of delirium differs when it occurs in the patient with an underlying dementia. We discuss the implications in terms of identification and management of this complex condition.

Sex Differences in Delirium after Coronary Artery Bypass Graft Surgery and Perioperative Neuropsychiatric Conditions: A Secondary Analysis of a Cohort Study.

BACKGROUND: Biological sex influences the risk of depression and cognitive impairment, but its role in relation to postoperative delirium is unclear. This analysis investigates sex differences in delirium risk after coronary artery bypass graft (CABG) surgery and sex-related differences in relation to affective and cognitive symptoms. METHODS: This is a secondary analysis of the Neuropsychiatric Outcomes After Heart Surgery (NOAHS) study, a single-site, observational study of a CABG surgery cohort (n = 149). Preoperative characteristics are stratified by sex, and baseline variables that differ by sex are evaluated to understand whether sex modifies their relationships with delirium. We also evaluate sex differences in one-month depression and cognition. RESULTS: Female sex is associated with several delirium risk factors, including higher risk of preoperative depression and middle cerebral artery (MCA) stenosis. MCA stenosis was statistically associated with delirium only among women (OR 15.6, 95% CI 1.5, 164.4); mild cognitive impairment (MCI) was associated with delirium only in men (OR 4.6, 95% CI 1.2, 17.9). Other sex-based differences failed to reach statistical significance. Depression remained commoner among women 1 month post-CABG. CONCLUSIONS: Women in this CABG cohort were more likely to have depression at baseline and 1 month postoperatively, as well as MCA stenosis and postoperative delirium. Sex might modify the relationship between post-CABG delirium and its risk factors including MCA stenosis and MCI. Cerebrovascular disease deserves study as a potential explanation linking female sex and a range of poor outcomes among women with coronary heart disease.

Practical Application of a Battery of Brief Tools to Evaluate Geriatric Medical Inpatients for the Three Ds.

OBJECTIVE: The investigators aimed to identify the clinical characteristics of patients with or without delirium and preexisting depression, dementia, both, or neither by using validated tools easily administered in clinical practice. METHODS: In this cross-sectional prospective observational study conducted in Medellín, Colombia, 200 geriatric inpatients were evaluated with the Delirium Diagnostic Tool-Provisional (DDT-Pro), Informant Questionnaire on Cognitive Decline in the Elderly, Hachinski Ischemic Scale, Cornell Scale for Depression in Dementia, and Charlson Comorbidity Index-short form. Delirium motor subtype, mortality, and length of hospital stay were assessed. RESULTS: The study included 134 patients without delirium (67%), 14 with delirium only (7%), 16 with delirium and dementia (8%), 13 with delirium and depression (7%), and 23 with delirium, dementia, and depression (the three Ds) (12%). Prevalence rates of dementia (59%) and depression (55%) among 66 patients with delirium were higher than prevalence rates among patients without delirium (13% and 28%, respectively), suggesting that both conditions are risk factors. Main medical diagnoses, mortality, and dementia type did not differ among groups. Motor subtypes were similar among delirium groups. Patients in the delirium groups, except those in the delirium and depression group, were older than patients without delirium. Medical burden was highest among the patients with delirium and dementia and those with all three conditions. Delirium and dementia were more severe when comorbid with each other. Depression was most severe among patients with delirium and depression. Patients with all three conditions had a longer length of hospital stay than those without delirium. CONCLUSIONS: Using brief tools to detect dementia and depression in conjunction with the DDT-Pro to assess delirium diagnosis and severity is feasible and enables a more in-depth evaluation of elderly hospitalized patients. Because previous longitudinal research suggests that these comorbid conditions influence prognosis following a delirium episode, better identification of the three Ds offers proactive interventional opportunities. Depression is an underrecognized risk factor for delirium.