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Background: Postoperative delirium (POD) is a serious complication following deep brain stimulation (DBS) but only received little attention. Its main risk factors are higher age and preoperative cognitive deficits. These are also main risk factors for long-term cognitive decline after DBS in Parkinson's disease (PD). Objective: To identify risk factors for POD severity after DBS surgery in PD. Methods: 57 patients underwent DBS (21 female; age 60.2±8.2; disease duration 10.5±5.9 years). Preoperatively, general, PD- and surgery-specific predictors were recorded. Montreal Cognitive Assessment and the neuropsychological test battery CANTAB ConnectTM were used to test domain-specific cognition. Volumes of the cholinergic basal forebrain were calculated with voxel-based morphometry. POD severity was recorded with the delirium scales Confusion Assessment Method for Intensive Care Unit (CAM-ICU) and Nursing Delirium Scale (NU-DESC). Spearman correlations were calculated for univariate analysis of predictors and POD severity and linear regression with elastic net regularization and leave-one-out cross-validation was performed to fit a multivariable model. Results: 21 patients (36.8%) showed mainly mild courses of POD following DBS. Correlation between predicted and true POD severity was significant (spearman rhoâ=â0.365, pâ=â0.001). Influential predictors were age (pâ<â0.001), deficits in attention and motor speed (pâ=â0.002), visual learning (pâ=â0.036) as well as working memory (pâ<â0.001), Nucleus basalis of Meynert volumes (pâ=â0.003) and burst suppression (pâ=â0.005). Conclusions: General but also PD- and surgery-specific factors were predictive of POD severity. These findings underline the multifaceted etiology of POD after DBS in PD. Valid predictive models must therefore consider general, PD- and surgery-specific factors.
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BACKGROUND: The aim of this study was to analyze four pre-operative physical frailty indicators from a geriatric assessment (GA) independently and combined in a physical frailty index, in their ability to predict postoperative 30 d-complications. MATERIALS AND METHODS: In this secondary analysis of data from the published PERATECS study (ClinicalTrials.gov: NCT01278537), the predictive value of four physical frailty indicators from a defined GA battery was examined with univariable and multivariate logistic regression models in a sample of 493 onco-geriatric surgical patients. The primary endpoint was incidence of major (Clavien-Dindo ≥ grade 2 [CD ≥ 2]) complications within 30 postoperative days. Predictors of the first model included self-reported exhaustion (SRE), body mass index (BMI), Timed Up-and-Go (TUG) and handgrip strength (HGS) independently, and a second model combined these four items as a Physical Frailty Index (4i-PFI). Both regression models were adjusted for age, gender, American Society of Anesthesiologists (ASA) status, tumor sites, duration of surgery time and Mini Nutritional Assessment (MNA) score. RESULTS: A total of 233 patients (47 %) developed CD ≥ 2 complications. In addition to ASA score, length of surgery, and gynecological and upper gastrointestinal tumor sites, the first model showed that SRE (OR 1.866) predicted CD ≥ 2 complications, but not TUG, BMI and HGS. In the second model, the 4i-PFI predicted CD ≥ 2 complications (OR pre-frail = 1.808, frail = 3.787). CONCLUSIONS: Physical frailty indicators as SRE revealed a better ability to predict CD ≥ 2 complications than BMI, TUG and HGS. However, prediction of CD ≥ 2 complications was enhanced when these parameters were combined in a novel 4i-PFI.
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Fragilidad , Evaluación Geriátrica , Fuerza de la Mano , Neoplasias , Complicaciones Posoperatorias , Autoinforme , Humanos , Femenino , Masculino , Anciano , Complicaciones Posoperatorias/epidemiología , Fragilidad/epidemiología , Neoplasias/cirugía , Incidencia , Fatiga/epidemiología , Fatiga/etiología , Anciano de 80 o más Años , Índice de Masa Corporal , Anciano FrágilRESUMEN
Past studies have observed that brain atrophy may accelerate after surgical procedures. Furthermore, an association of systemic inflammation with neurodegeneration has been described. We hypothesize that postoperative interleukin (IL) levels in circulation as well as the perioperative change in interleukin levels are associated with increased postoperative atrophy in the Nucleus basalis magnocellularis (of Meynert, NBM) which is the major source of cortical acetylcholine. We analyzed data from the BioCog cohort which included patients ≥ 65 years presenting for elective major surgery (≥ 60min). Blood samples were taken before surgery and on the first postoperative day. Magnetic resonance imaging of the brain and neuropsychological assessments were conducted before surgery and after three months follow-up. We used linear regression analysis to determine the association of three interleukins (IL6, IL8 and IL18) with NBM atrophy (in % volume change from baseline before surgery to follow-up), as well as to examine the associations of NBM atrophy and volume with postoperative cognitive ability and perioperative cognitive change. Receiver-operating curves were used to determine the prognostic value of preoperative interleukin levels. For IL8 (N = 97) and IL18 (N = 217), but not IL6 (N = 240), we observed significant associations of higher postoperative IL levels at the first postoperative day with higher NBM atrophy at three months after surgery. Subsequent analyses suggested that in both IL8 and IL18, this association was driven by a more general association of chronically elevated IL levels and NBM atrophy, reflected by preoperative IL concentrations, rather than IL response to surgery, measured as the difference between pre- and postoperative IL concentrations. At follow-up, NBM volume was positively associated with the level of cognitive performance, but NBM atrophy was not significantly related to perioperative cognitive change. Prognostic value of preoperative IL concentrations for NBM atrophy was low. Our results suggest that an association of postoperative interleukin levels with NBM atrophy is driven by preoperatively elevated interleukins due to pre-existing inflammation, rather than perioperative change in interleukin levels in response to surgery and anesthesia. The BioCog study has been registered at clinicaltrials.gov on Oct 15, 2014 (NCT02265263).
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Núcleo Basal de Meynert , Interleucina-18 , Humanos , Atrofia/patología , Núcleo Basal de Meynert/patología , Núcleo Basal de Meynert/fisiología , Inflamación/patología , Interleucina-8 , AncianoRESUMEN
BACKGROUND: Beta-blocker (BB) therapy plays a central role in the treatment of cardiovascular diseases. An increasing number of patients with cardiovascular diseases undergoe noncardiac surgery, where opioids are an integral part of the anesthesiological management. There is evidence to suggest that short-term intravenous BB therapy may influence perioperative opioid requirements due to an assumed cross-talk between G-protein coupled beta-adrenergic and opioid receptors. Whether chronic BB therapy could also have an influence on perioperative opioid requirements is unclear. METHODS: A post hoc analysis of prospectively collected data from a multicenter observational (BioCog) study was performed. Inclusion criteria consisted of elderly patients (≥ 65 years) undergoing elective noncardiac surgery as well as total intravenous general anesthesia without the use of regional anesthesia and duration of anesthesia ≥ 60 min. Two groups were defined: patients with and without BB in their regular preopreative medication. The administered opioids were converted to their respective morphine equivalent doses. Multiple regression analysis was performed using the morphine-index to identify independent predictors. RESULTS: A total of 747 patients were included in the BioCog study in the study center Berlin. 106 patients fulfilled the inclusion criteria. Of these, 37 were on chronic BB. The latter were preoperatively significantly more likely to have arterial hypertension (94.6%), chronic renal failure (27%) and hyperlipoproteinemia (51.4%) compared to patients without BB. Both groups did not differ in terms of cumulative perioperative morphine equivalent dose (230.9 (BB group) vs. 214.8 mg (Non-BB group)). Predictive factors for increased morphine-index were older age, male sex, longer duration of anesthesia and surgery of the trunk. In a model with logarithmised morphine index, only gender (female) and duration of anesthesia remained predictive factors. CONCLUSIONS: Chronic BB therapy was not associated with a reduced perioperative opioid consumption. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov ( NCT02265263 ) on the 15.10.2014 with the principal investigator being Univ.-Prof. Dr. med. Claudia Spies.
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Analgésicos Opioides , Enfermedades Cardiovasculares , Humanos , Masculino , Femenino , Anciano , Analgésicos Opioides/uso terapéutico , Morfina , Dolor Postoperatorio/tratamiento farmacológicoRESUMEN
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.
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Disfunción Cognitiva , Delirio , Imagen por Resonancia Magnética , Complicaciones Posoperatorias , Humanos , Femenino , Masculino , Anciano , Disfunción Cognitiva/etiología , Disfunción Cognitiva/fisiopatología , Delirio/etiología , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Anciano de 80 o más Años , Complicaciones Cognitivas PostoperatoriasRESUMEN
Background: The Trail Making Test B (TMT-B) is indicative of cognitive flexibility and several other cognitive domains. Previous studies suggest that it might be associated with the risk of developing postoperative delirium, but evidence is limited and conflicting. We therefore aimed to replicate the association of preoperative TMT-B results with postoperative delirium. Methods: We included older adults (≥65 yr) scheduled for major surgery and without signs of dementia to participate in this binational two-centre longitudinal observational cohort study. Presurgical TMT-B scores were obtained. Delirium was assessed twice daily using validated instruments. Logistic regression was applied and the area under the receiver operating characteristic curve calculated to determine the predictive performance of TMT-B. We subsequently included covariates used in previous studies for consecutive sensitivity analyses. We further analysed the impact of outliers, missing or impaired data. Results: Data from 841 patients were included and of those, 151 (18%) developed postoperative delirium. TMT-B scores were statistically significantly associated with the incidence of postoperative delirium {odds ratio per 10-s increment 1.06 (95% confidence interval [CI] 1.02-1.09), P=0.001}. The area under the receiver operating characteristic curve was 0.60 ([95% CI 0.55-0.64], P<0.001). The association persisted after removing 21 outliers (1.07 [95% CI 1.03-1.07], P<0.001). Impaired or missing TMT-B data (n=88) were also associated with postoperative delirium (odds ratio 2.74 [95% CI 1.71-4.35], P<0.001). Conclusions: The TMT-B was associated with postoperative delirium, but its predictive performance as a stand-alone test was low. The TMT-B alone is not suitable to predict delirium in a clinical setting. Clinical trial registration: NCT02265263. (https://clinicaltrials.gov/ct2/show/results/NCT02265263).
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A growing body of literature suggests the important role of the thalamus in cognition and neurodegenerative diseases. This study aims to elucidate whether the preoperative thalamic volume is associated with preoperative cognitive impairment (preCI) and whether it is predictive for postoperative cognitive dysfunction at 3 months (POCD). We enrolled 301 patients aged 65 or older and without signs of dementia who were undergoing elective surgery. Magnetic resonance imaging was conducted prior to surgery. Freesurfer (version 5.3.) was used to automatically segment the thalamus volume. A neuropsychological test battery was administered before surgery and at a 3 month follow-up. It included the computerized tests Paired Associate Learning (PAL), Verbal Recognition Memory (VRM), Spatial Span Length (SSP), Simple Reaction Time (SRT), the pen-and-paper Trail-Making-Test (TMT) and the manual Grooved Pegboard Test (GPT). Using a reliable change index, preCI and POCD were defined as total Z-score > 1.96 (sum score over all tests) and/or Z-scores > 1.96 in ≥ 2 individual cognitive test parameters. For statistical analyses, multivariable logistic regression models were applied. Age, sex and intracranial volume were covariates in the models. Of 301 patients who received a presurgical neuropsychological testing and MRI, 34 (11.3%) had preCI. 89 patients (29.5%) were lost to follow-up. The remaining 212 patients received a follow-up cognitive test after 3 months, of whom 25 (8.3%) presented with POCD. Independently of age, sex and intracranial volume, neither preCI (OR per cm3 increment 0.81 [95% CI 0.60-1.07] p = 0.14) nor POCD (OR 1.02 per cm3 increment [95% CI 0.75-1.40] p = 0.87) were statistically significantly associated with patients' preoperative thalamus volume. In this cohort we could not show an association of presurgical thalamus volume with preCI or POCD.Clinical Trial Number: NCT02265263 ( https://clinicaltrials.gov/ct2/show/results/NCT02265263 ).
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Trastornos del Conocimiento , Disfunción Cognitiva , Complicaciones Cognitivas Postoperatorias , Humanos , Cognición , Trastornos del Conocimiento/patología , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/etiología , Pruebas Neuropsicológicas , Complicaciones Posoperatorias/diagnósticoRESUMEN
Background: Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) are postoperative neurocognitive disorders (PNDs) that frequently occur in the aftermath of a surgical intervention. Cognitive reserve (CR) is a concept posited to explain why cognitive health varies between individuals. On this qualitative understanding of cognitive health, factors like IQ, education level, and occupational complexity can affect the impact of neuropathological processes on cognitive outcomes. Methods: We investigated the association between CR and POD and CR and POCD on data from 713 patients aged≥65 years with elective surgery. Peak pre-morbid IQ was estimated from vocabulary. Occupational complexity was coded according to the Dictionary of Occupational Titles (DOT). Education level was classed according to the International Standard Classification of Education (ISCED). These three factors were used as proxies of CR. In a series of regression models, age, sex, depression, site of surgery, and several lifestyle and vascular factors were controlled for. Results: Patients with a higher IQ had lower odds of developing POD. We found no significant association between the other two CR markers with POD. None of the CR markers was associated with POCD. Conclusion: The significant association of a higher IQ with lower POD risk allows for the stratification of elderly surgical patients by risk. This knowledge can aid the prevention and/or early detection of POD. Further research should attempt to determine the lack of associations of CR markers with POCD in our study.
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In order to prevent short-term complication, patients with frailty syndrome require special attention and care in the perioperative context. The implementation of a frailty screening and if possible, an advanced geriatric assessment in the clinical routine should take into account the clinical setting, the patient population as well as time and human resources. Individual treatment pathways must allow for a multidisciplinary exchange and a multimodal approach when dealing with these challenging patients. Key aspects of such pathways include physiotherapeutic interventions, nutritional counselling, adequate pain medication, delirium prevention, patient blood management and extended perioperative monitoring. An interdisciplinary shared decision-making process together with patients can help develop realistic and individual treatment concepts to improve safety and outcome of frail patients.
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Fragilidad , Humanos , Anciano , Fragilidad/diagnóstico , Fragilidad/terapia , Anciano Frágil , Evaluación Geriátrica , DolorRESUMEN
BACKGROUND: Previous studies suggest a role of the thalamus in cognitive function, while others implicate it as a central effect site of anesthetics. Yet, its role in postoperative neurocognition in the aging brain remains uncertain. We used presurgical thalamic volume as a functional indicator and determined its association with postoperative delirium (POD). METHODS: For this study, 301 older adults (aged ≥65) without dementia and scheduled for surgery were enrolled. Before surgery, participants underwent magnetic resonance imaging (MRI). Thalamus volume was segmented using Freesurfer (Version 5.3.). Participants were screened for POD twice a day until discharge or for a maximum of 7 days. POD was defined as a positive screening on ≥1 of 4 validated instruments: Richmond Agitation Sedation Scale (RASS), Nursing Delirium Screening Scale (Nu-DESC), Confusion Assessment Method (CAM), and Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) score. A logistic regression associated thalamus volume with POD with adjustment for age, global brain atrophy, and physical status according to the American Society of Anesthesiologists (ASA) classification. RESULTS: In this cohort, 44 participants (14.6%) were diagnosed with POD. Independently of age, global brain atrophy, and physical status score, a higher preoperative thalamus volume was associated with a reduced odds of POD (odds ratio per 1-cm3 increment; 0.73 [95% confidence interval (CI), 0.58-0.92]; P = .008). CONCLUSIONS: A larger thalamus volume was associated with reduced odds of POD. Thus, the thalamus marks a region of interest in POD in the aging brain. These findings may help to understand the neuronal basis of POD.
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Delirio , Anciano , Atrofia , Estudios de Cohortes , Delirio/diagnóstico , Delirio/etiología , Humanos , Unidades de Cuidados Intensivos , Complicaciones Posoperatorias/diagnóstico por imagen , Complicaciones Posoperatorias/etiología , Tálamo/diagnóstico por imagenRESUMEN
BACKGROUND: Studies suggest that a higher education and occupation are each associated with a higher late-life cognitive ability, but their inter-relationships in their association with cognitive ability and the contribution of peak IQ in young adulthood ('pre-morbid IQ') often remain unclear. METHODS: Cross-sectional analysis of 623 participants aged ≥65 years of the BioCog study. Education was coded according to the International Standard Classification of Education (ISCED; range 1 to 6). Occupation was coded as 'semi/unskilled', 'skilled manual', 'skilled non-manual', 'managerial', 'professional'. A summary score of global ability ('g') was constructed from six cognitive tests. Pre-morbid IQ was estimated from vocabulary. The Geriatric Depression Scale assessed symptoms of depression. Age- and sex-adjusted analyses of covariance were performed. RESULTS: Education (partial eta2 0.076; p < 0.001) and occupation (partial eta2 = 0.037; p < 0.001) were each significantly associated with g. For education, the association was attenuated but remained statistically significant when pre-morbid IQ was controlled for (partial eta2 0.036; p < 0.001) and was unchanged with additional adjustment for depression (partial eta2 0.037; p < 0.001). For occupation, the association with g was no longer significant when pre-morbid IQ (partial eta2 = 0.015; p = 0.06) and depression (partial eta2 = 0.011; p = 0.18) were entered as covariates in separate steps. When education and occupation were entered concurrently into the fully adjusted model, only education was independently associated with g (partial eta2 0.030; p < 0.001; occupation, p = 0.93). CONCLUSION: While a higher education and a higher occupation were each associated with a higher late-life cognitive ability, only for education some unique contribution to cognitive ability remained over and above its relationship with pre-morbid IQ, depression, and occupation. Further research is needed to address whether a longer time spent in education may promote late-life cognitive ability.
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Cognición , Ocupaciones , Adulto , Anciano , Estudios Transversales , Escolaridad , Humanos , Pruebas Neuropsicológicas , Adulto JovenRESUMEN
Postoperative delirium (POD) and postoperative (neuro-)cognitive disorder (POCD) are frequent and serious complications after operations. We aim to investigate the association between pre-operative polypharmacy and potentially inappropriate medications and the development of POD/POCD in elderly patients. This investigation is part of the European BioCog project (www.biocog.eu), a prospective multicenter observational study with elderly surgical patients. Patients with a Mini-Mental State Examination score less than or equal to 23 points were excluded. POD was assessed up to 7 days after surgery using the Nursing Delirium Screening Scale, Confusion Assessment Method (for the intensive care unit [ICU]), and a patient chart review. POCD was assessed 3 months after surgery with a neuropsychological test battery. Pre-operative long-term medication was evaluated in terms of polypharmacy (≥5 agents) and potentially inappropriate medication (defined by the PRISCUS and European list of potentially inappropriate medications [EU(7)-PIM] lists), and associations with POD and POCD were analyzed using logistic regression analysis. Eight hundred thirty-seven participants were included for analysis of POD and 562 participants for POCD. Of these, 165 patients (19.7%) fulfilled the criteria of POD and 60 (10.7%) for POCD. After adjusting for confounders, pre-operative polypharmacy and intake of potentially inappropriate medications could not be shown to be associated with the development of POD nor POCD. We found no associations between pre-operative polypharmacy and potentially inappropriate medications and development of POD and POCD. Future studies should focus on the evaluation of drug interactions to determine whether patients benefit from a pre-operative adjustment.
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Delirio del Despertar/epidemiología , Complicaciones Cognitivas Postoperatorias/epidemiología , Anciano , Delirio del Despertar/diagnóstico , Delirio del Despertar/etiología , Femenino , Humanos , Masculino , Pruebas de Estado Mental y Demencia , Polifarmacia , Complicaciones Cognitivas Postoperatorias/diagnóstico , Complicaciones Cognitivas Postoperatorias/etiología , Lista de Medicamentos Potencialmente Inapropiados , Periodo Preoperatorio , Estudios ProspectivosRESUMEN
BACKGROUND: Postoperative cognitive dysfunction (POCD) is an adverse outcome that impacts patients' quality of life. Its diagnosis relies on formal cognitive testing performed before and after surgery. The substantial heterogeneity in methodology limits comparability and meta-analysis of studies. This systematic review critically appraises the methodology of studies on POCD published since the 1995 Consensus Statement and aims to provide guidance to future authors by providing recommendations that may improve comparability between future studies. METHODS: This systematic review of literature published between 1995 and 2019 included studies that used baseline cognitive testing and a structured cognitive test battery, and had a minimal follow-up of 1 month. For cohorts with multiple publications, data from the primary publication were supplemented with available data from later follow-up studies. RESULTS: A total of 274 unique studies were included in the analysis. In the included studies, 259 different cognitive tests were used. Studies varied considerably in timing of assessment, follow-up duration, definition of POCD, and use of control groups. Of the 274 included studies, 70 reported POCD as a dichotomous outcome at 1 to <3 months, with a pooled incidence of 2998/10 335 patients (29.0%). CONCLUSIONS: We found an overwhelming heterogeneity in methodology used to study POCD since the publication of the 1995 Consensus Statement. Future authors could improve study quality and comparability through optimal timing of assessment, the use of commonly used cognitive tests including the Consensus Statement 'core battery', application of appropriate cut-offs and diagnostic rules, and detailed reporting of the methods used. PROSPERO REGISTRY NUMBER: CRD42016039293.
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Cognición , Pruebas Neuropsicológicas , Complicaciones Cognitivas Postoperatorias/diagnóstico , Humanos , Complicaciones Cognitivas Postoperatorias/etiología , Complicaciones Cognitivas Postoperatorias/psicología , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Proyectos de Investigación , Factores de TiempoRESUMEN
Postoperative delirium (POD) represents a confusional state during days/weeks after surgery and is particularly frequent in elderly patients. Hardly any fMRI studies were conducted to understand the underlying pathophysiology of POD patients. This prospective observational cohort study aims to examine changes of specific resting-state functional connectivity networks across different time points (pre- and 3-5 months postoperatively) in delirious patients compared to no-POD patients. Two-hundred eighty-three elderly surgical patients underwent preoperative resting-state fMRI (46 POD). One-hundred seventy-eight patients completed postoperative scans (19 POD). For functional connectivity analyses, three functional connectivity networks with seeds located in the orbitofrontal cortex (OFC), nucleus accumbens (NAcc), and hippocampus were investigated. The relationship of POD and connectivity changes between both time points (course connectivity) were examined (ANOVA). Preoperatively, delirious patients displayed hyperconnectivities across the examined functional connectivity networks. In POD patients, connectivities within NAcc and OFC networks demonstrated a decrease in course connectivity [max. F = 9.03, p = 0.003; F = 4.47, p = 0.036, resp.]. The preoperative hyperconnectivity in the three networks in the patients at risk for developing POD could possibly indicate existing compensation mechanisms for subtle brain dysfunction. The observed pathophysiology of network function in POD patients at least partially involves dopaminergic pathways.
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Delirio , Anciano , Humanos , Imagen por Resonancia Magnética , Corteza Prefrontal , Estudios Prospectivos , DescansoRESUMEN
BACKGROUND: Anecdotally, cholinergic stimulation has been used to treat delirium and reduce cognitive dysfunction. OBJECTIVE: The aim of this investigation was to evaluate whether physostigmine reduced the incidence of postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) in patients undergoing liver resection. DESIGN: This was a double-blind, randomised, placebo-controlled trial. Between 11 August 2009 and 3 March 2016, patients were recruited at the Charité - Universitätsmedizin Berlin in Germany. Follow-ups took place at 1 week (T1), 90 days (T2) and 365 days (T3) after surgery. SETTING: This single-centre study was conducted at an academic medical centre. PARTICIPANTS: In total, 261 participants aged at least 18âyears scheduled for elective liver surgery were randomised. The protocol also included 45 non-surgical matched controls to provide normative data for POCD and neurocognitive deficit (NCD). INTERVENTION: Participants were allocated to receive either intravenous physostigmine, as a bolus of 0.02âmgâkg-1 body weight followed by 0.01âmgâkg-1 body weight per hour (nâ=â130), or placebo (nâ=â131), for 24âh after induction of anaesthesia. MAIN OUTCOMES AND MEASURES: Primary outcomes were POD, assessed using the Diagnostic and Statistical Manual of Mental Disorders (DSM-4-TR) twice daily up to day 7 after surgery, and POCD assessed via the CANTAB neuropsychological test battery, and two paper pencil tests on the day before surgery, and on postoperative days 7, 90 and 365. RESULTS: In total, 261 patients were randomised, 130 to the physostigmine and 131 to the placebo group. The incidence of POD did not differ significantly between the physostigmine and placebo groups (20 versus 15%; Pâ=â0.334). Preoperative cognitive impairment and POCD frequencies did not differ significantly between the physostigmine and placebo groups at any time. Lower mortality rates were found in the physostigmine group compared with placebo at 3âmonths [2% (95% confidence interval (CI), 0 to 4) versus 11% (95% CI, 6 to 16), Pâ=â0.002], and 6âmonths [7% (95% CI, 3 to 12) versus 16% (95% CI, 10 to 23), Pâ=â0.012] after surgery. CONCLUSION: Physostigmine had no effect on POD and POCD when applied after induction of anaesthesia up to 24âh. TRIAL REGISTRATION: DOI 10.1186/ISRCTN18978802, EudraCT 2008-007237-47, Ethics approval ZS EK 11â618/08 (15 January 2009).
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Disfunción Cognitiva , Delirio , Adolescente , Adulto , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/etiología , Disfunción Cognitiva/prevención & control , Delirio/diagnóstico , Delirio/epidemiología , Delirio/prevención & control , Humanos , Hígado , Fisostigmina , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & controlRESUMEN
BACKGROUND: A pre-existing neurocognitive disorder (NCD) is a relevant factor for the outcome of surgical patients. To improve understanding of these conditions, we investigated the association between parameters of the cholinergic system and NCD. METHOD: This investigation is part of the BioCog project (www.biocog.eu), which is a prospective multicenter observational study including patients aged 65 years and older scheduled for elective surgery. Patients with a Mini-Mental State Examination (MMSE) score ≤23 points were excluded. Neurocognitive disorder was assessed according to the fifth Diagnostic and Statistical Manual of Mental Disorders criteria. The basal forebrain cholinergic system volume (BFCSV) was assessed with magnetic resonance imaging, the peripheral cholinesterase (ChE) activities with point-of-care measurements, and anticholinergic load by analyzing the long-term medication with anticholinergic scales (Anticholinergic Drug Scale [ADS], Anticholinergic Risk Scale [ARS], Anticholinergic Cognitive Burden Scale [ACBS]). The associations of BFCSV, ChE activities, and anticholinergic scales with NCD were studied with logistic regression analysis, adjusting for confounding factors. RESULTS: A total of 797 participants (mean age 72 years, 42% females) were included. One hundred and eleven patients (13.9%) fulfilled criteria for mild NCD and 82 patients (10.3%) for major NCD criteria. We found that AcetylChE activity was associated with major NCD (odds ratio [95% confidence interval]: [U/gHB] 1.061 [1.010, 1.115]), as well as ADS score ([points] 1.353 [1.063, 1.723]) or ARS score, respectively ([points] 1.623 [1.100, 2.397]) with major NCD. However, we found no association between BFCSV or ButyrylChE activity with mild or major NCD. CONCLUSIONS: AcetylChE activity and anticholinergic load were associated with major NCD. Future research should focus on the association of the cholinergic system and the development of postoperative delirium and postoperative NCD.
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Antagonistas Colinérgicos/uso terapéutico , Neuronas Colinérgicas/fisiología , Trastornos Neurocognitivos/fisiopatología , Periodo Preoperatorio , Acetilcolinesterasa/metabolismo , Anciano , Prosencéfalo Basal/diagnóstico por imagen , Prosencéfalo Basal/efectos de los fármacos , Prosencéfalo Basal/metabolismo , Antagonistas Colinérgicos/efectos adversos , Neuronas Colinérgicas/efectos de los fármacos , Neuronas Colinérgicas/patología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Trastornos Neurocognitivos/inducido químicamente , Trastornos Neurocognitivos/etiología , Trastornos Neurocognitivos/patología , Neuroimagen , Estudios ProspectivosRESUMEN
BACKGROUND: In the perioperative course, alcohol withdrawal syndrome (AWS) can occur in any setting, especially in aero-digestive and acute trauma surgery. Challenging issues are the overlap of other forms of delirium in perioperative and intensive care settings as well as general anesthesia masking the onset of withdrawal symptoms. In contrast to other etiologies of delirium, the pathophysiology and thus treatment strategy of AWS is different: the key point is the tolerance to GABAergic molecules of alcohol-dependent subjects resulting in central nervous hyperactivity once the effect of alcohol or other GABA-stimulating agents is decreased. SUMMARY: Despite limitations due to insufficient accuracy of self-reporting questionnaires and limited feasibility in emergency settings, the AUDIT and the shortened AUDIT-C are the standard tools for detection of alcohol use disorders (AUD), as well as predicting AWS risk and severity in approximately half of these AUD patients. The most important risk factors for AWS are a high blood alcohol concentration at hospital admission, AWS episodes in medical history, and lack of control of alcohol use. Patients considered at risk for severe AWS must be treated with prophylactic medication before the onset of symptoms. Thiamine supplementation is required for all malnourished alcohol-dependent patients. Writing down alcohol-related diagnoses in the medical records requires the patient's presumed consent after shared decision-making. These reports should remain strictly confidential if the patient desires. Psychological support for the perioperative period as well as the following course should be offered to all AUD patients including support in short- and long-term detoxification. Alternative diagnoses must be ruled out with no timely delay, especially if fever and coma are the leading symptoms. The backbone of AWS therapy is the symptom-triggered administration of intravenous benzodiazepines (BZO) in escalating doses until the aimed revised Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWA-Ar) or Richmond Agitation-Sedation Scale (RASS) score is achieved. Clonidine, dexmedetomidine, baclofen, ketamine, and neuroleptics may be used as symptom-orientated adjuncts. The therapeutic administration of ethanol or clomethiazole is considered to be harmful in critically ill patients after the onset of AWS. General supportive and intensive care including high-dose thiamine supplementation are mandatory in severe AWS cases. The timely differential diagnosis of delirium is important - and AWS is a diagnosis of exclusion - because BZO are strongly recommended for AWS patients but may not be the treatment of choice in other etiologies of delirium. KEY MESSAGES: Screening for AWS risk factors should be integrated in the preoperative and emergency assessment. Other severe diagnoses must be ruled out before the diagnosis of AWS can be established. Preventive treatment should be given to high-risk patients scoring positive for AUD and for patients with a lack of alcohol use control. The principles of AWS therapy are symptom-orientated doses of BZO and as adjuncts α2-agonists, neuroleptics, and others guided by repeated reassessment with validated tools and thiamine administration. Length of stay and morbidity are reduced if AWS therapy is symptom-orientated and protocol-based.
RESUMEN
Objective: Age-related disorders, such as dementia, significantly contribute to the global burden of disease. Adequate screening in the primary care setting is critical for early detection and proper management. The Addenbrooke's Cognitive Examination III (ACE-III) is an open-source neuropsychological test with superior diagnostic quality in comparison to the Mini-Mental State Examination (MMSE). Our aim was to perform a guideline-conform English-German translation and cultural adaptation of the ACE-III in order to enable implementation in German-speaking countries. Methods: The translation and cultural adaptation were performed in accordance with the "Principles of Good Practice for the Translation and Cultural Adaptation Process for Patient-Reported Outcomes (PRO) Measures" from the International Society for Pharmacoeconomics and Outcome Research (ISPOR) (Wild et al. 2005). Four separate English-German translations were compiled into one German consensus translation, which was then translated back into English and compared to the original English version. After comparison, the German consensus translation was revised with emphasis on the identified differences between the English original version and the English translated version. This revised German consensus translation was subsequently evaluated for clinical applicability on a 5-point scale (0 - not applicable; 5 - applicable without any restrictions) by 20 practitioners experienced in the field of neuropsychological testing, using an anonymized, paper-based 22-item survey. Results: Nineteen of the 20 practitioners (95.0%) rated the German ACE-III translation as overall applicable. The median rating was 4.0 [IQR (4.0/5.0)]. When evaluating survey items assessing the applicability of the individual 19 subtests of the ACE-III, all of them (100%) were rated as applicable with a median rating of 4.5 [IQR (4.1/4.9)]. Conclusion: The German ACE-III translation in its current form is generally applicable and can be utilized for clinical and scientific purposes.
Asunto(s)
Demencia , Pruebas Neuropsicológicas/normas , Atención Primaria de Salud/métodos , Traducciones , Anciano , Comparación Transcultural , Demencia/diagnóstico , Demencia/epidemiología , Demencia/psicología , Diagnóstico Precoz , Femenino , Alemania/epidemiología , Carga Global de Enfermedades , Humanos , Masculino , Psicometría , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , TraducciónRESUMEN
OBJECTIVE: Studies of postoperative cognitive dysfunction (POCD) rely on repeat neuropsychological testing. The stability of the applied instruments, which are affected by natural variability in performance and measurement imprecision, is often unclear. We determined the stability of a neuropsychological test battery using a sample of older adults from the general population. Forty-five participants aged 65 to 89 years performed six computerized and non-computerized neuropsychological tests at baseline and again at 7 day and 3 months follow-up sessions. Mean scores on each test were compared across time points using repeated measures analyses of variance (ANOVA) with pairwise comparison. Two-way mixed effects, absolute agreement analyses of variance intra-class correlation coefficients (ICC) determined test-retest reliability. RESULTS: All tests had moderate to excellent test-retest reliability during 7-day (ICC range 0.63 to 0.94; all p < 0.01) and 3-month intervals (ICC range 0.60 to 0.92; all p < 0.01) though confidence intervals of ICC estimates were large throughout. Practice effects apparent at 7 days eased off by 3 months. No substantial differences between computerized and non-computerized tests were observed. We conclude that the present six-test neuropsychological test battery is appropriate for use in POCD research though small sample size of our study needs to be recognized as a limitation. Trial registration ClinicalTrials.gov Identifier NCT02265263 (15th October 2014).