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Background: Delirium affects > 15% of hospitalised patients but is grossly underdetected, contributing to poor care. The 4 'A's Test (4AT, www.the4AT.com ) is a short delirium assessment tool designed for routine use without special training. The primary objective was to assess the accuracy of the 4AT for delirium detection. The secondary objective was to compare the 4AT with another commonly used delirium assessment tool, the Confusion Assessment Method (CAM)., Methods: This was a prospective diagnostic test accuracy study set in emergency departments or acute medical wards involving acute medical patients aged ≥ 70. All those without acutely life-threatening illness or coma were eligible. Patients underwent (1) reference standard delirium assessment based on DSM-IV criteria and (2) were randomised to either the index test (4AT, scores 0-12; prespecified score of > 3 considered positive) or the comparator (CAM; scored positive or negative), in a random order, using computer-generated pseudo-random numbers, stratified by study site, with block allocation. Reference standard and 4AT or CAM assessments were performed by pairs of independent raters blinded to the results of the other assessment., Results: Eight hundred forty-three individuals were randomised: 21 withdrew, 3 lost contact, 32 indeterminate diagnosis, 2 missing outcome, and 785 were included in the analysis. Mean age was 81.4 (SD 6.4) years. 12.1% (95/785) had delirium by reference standard assessment, 14.3% (56/392) by 4AT, and 4.7% (18/384) by CAM. The 4AT had an area under the receiver operating characteristic curve of 0.90 (95% CI 0.84-0.96). The 4AT had a sensitivity of 76% (95% CI 61-87%) and a specificity of 94% (95% CI 92-97%). The CAM had a sensitivity of 40% (95% CI 26-57%) and a specificity of 100% (95% CI 98-100%)., Conclusions: The 4AT is a short, pragmatic tool which can help improving detection rates of delirium in routine clinical care., Trial Registration: International standard randomised controlled trial number (ISRCTN) 53388093 . Date applied 30/05/2014; date assigned 02/06/2014.

Objectives: The aim of this double-blinded randomised placebo-controlled trial was to investigate the efficacy of clonidine for delirium in medical inpatients greater than 65 years., Methods: Acutely admitted medical patients greater than 65 years with delirium or subsyndromal delirium were eligible for inclusion. Included patients were given a loading dose of either placebo or clonidine; 75 μg every third hour up to a maximum of four doses to reach steady state and further 75 μg twice daily until delirium free for 2 days, discharge or a maximum of 7 days of treatment. The primary endpoint was the trajectory of the Memorial Delirium Assessment Scale (MDAS) for the 7 days of treatment. Presence of delirium according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria and severity measured by MDAS were assessed daily until discharge or a maximum of 7 days after end of treatment., Results: Because of slower enrolment than anticipated, the study was halted early. Ten patients in each group were studied. The low recruitment rate was mainly due to the presence of multiple patient exclusion criteria for patient safety. There was no significant difference between the treatment group in the primary endpoint comparing the trajectory of MDAS for the 7 days of treatment using mixed linear models with log transformation, (P = .60). The treatment group did not have increased adverse effects., Conclusions: No effect of clonidine for delirium was found, although the study was under powered. Further studies in less frail populations are now required., (© 2019 John Wiley & Sons, Ltd.)

ABSTRACTDiagnosing delirium superimposed on dementia (DSD) remains challenging because of a lack of specific tools, though motor dysfunction in delirium has been relatively under-explored. This study aimed to use dysfunction in balance and mobility (with the Hierarchical Assessment of Balance And Mobility: HABAM) to identify DSD. This is a cross-sectional multicenter study, recruiting consecutive patients ≥70 years admitted to five acute or rehabilitation hospitals in Ireland, Italy, Portugal, and Switzerland. Delirium was diagnosed using DSM-5 criteria; dementia was determined by the Mini-Mental State Examination and the Questionnaire of Cognitive Decline in the Elderly. HABAM score was recorded at admission. Out of 114 patients (mean age ± SD = 82 ± 7; 54% female), dementia alone was present in 24.6% (n = 28), delirium alone in 18.4% (n = 21) and DSD in 27.2% (n = 31). Patients with DSD had a mean HABAM score 7 points greater than those with dementia alone (19.8 ± 8.7 vs 12.5 ± 9.5; p < 0.001); 70% of participants with DSD were correctly identified using the HABAM at a cut off of 22 (sensitivity 61%, specificity 79%, AUC = 0.76). Individuals with delirium have worse motor function than those without delirium, even in the context of comorbid dementia. Measuring motor function using the HABAM in older people at admission may help to diagnose DSD.

Delirium, one of the most common manifestations of acute brain dysfunction, is a serious complication in patients receiving care throughout the hospital and a strong predictor of worse outcome. Although delirium monitoring is advocated in numerous evidence-based guidelines as part of routine clinical care, it is still not widely and consistently performed at the bedside in different patient care settings. In a debate on delirium monitoring in hospitalized patients at the 7th American Delirium Society meeting in Nashville, Tennessee, June 2017, areas related to the feasibility, acceptability, and effectiveness of routine delirium monitoring of hospitalized patients were identified, and arguments both for (pro) and against (con) the practice were presented. These arguments and others arising in the discussion were subsequently expanded. The goals were to present a conversation among clinicians and researchers from different settings and to identify the evidence-practice gaps for delirium monitoring for future research and organizational quality improvement programs. Further research is needed to determine whether or not delirium monitoring should become routine clinical care for every patient in every hospital setting.

ABSTRACTBackground:Delirium is heterogeneous and can vary by etiology., Objectives: We sought to determine how delirium subtyped by etiology affected six-month function and cognition., Design: Prospective cohort study., Setting: Tertiary care, academic medical center., Participants: A total of 228 hospitalized patients > 65 years old were admitted from the emergency department (ED)., Measurements: The modified Brief Confusion Assessment Method was used to determine delirium in the ED. Delirium etiology was determined by three trained physician reviewers using a Delirium Etiology checklist. Pre-illness and six-month function and cognition were determined using the Older American Resources and Services Activities of Daily Living (OARS ADL) questionnaire and the short-form Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Multiple linear regression was performed to determine if delirium etiology subtypes were associated with six-month function and cognition adjusted for baseline OARS ADL and IQCODE. Two-factor interactions were incorporated to determine pre-illness function or cognition-modified relationships between delirium subtypes and six-month function and cognition., Results: In patients with poorer pre-illness function only, delirium secondary to metabolic disturbance (β coefficient = -2.9 points, 95%CI: -0.3 to -5.6) and organ dysfunction (β coefficient = -4.3 points, 95%CI: -7.2 to -1.4) was significantly associated with poorer six-month function. In patients with intact cognition only, delirium secondary to central nervous system insults was significantly associated with poorer cognition (β coefficient = 0.69, 95%CI: 0.19 to 1.20)., Conclusions: Delirium is heterogeneous and different etiologies may have different prognostic implications. Furthermore, the effect of these delirium etiologies on outcome may be dependent on the patient's pre-illness functional status and cognition.

Purpose: Delirium in the ICU is under-diagnosed. We evaluated feasibility and performance of a novel smartphone-based test for objectively detecting inattention in delirium., Material and Methods: DelApp-ICU combines a behavioural assessment and an attention task, whereby participants follow simple commands and count serially presented circles (score range 0-12, lower scores indicating worse performance). We assessed feasibility through staff interviews. Then we performed a preliminary case-control study in patients with and without delirium (ascertained with the Confusion Assessment Method for the ICU) who underwent the DelApp-ICU on up to 4 days., Results: Forty-six patients (median age = 57.5 years, range 18-83) were assessed 89 times in total (N's = 46, 29, 10 and 4 for subsequent assessments; 33.7% delirious). DelApp-ICU scores were lower in delirium (N = 20; median = 0.5, Inter-Quartile Range (IQR) = 0-4.75) compared to no delirium (N = 26, median = 12, IQR = 8-12) on days 1, 2 and 3 (p < 0.001, p < 0.001 and p < 0.05, respectively). A DelApp-ICU score ≤6 was 100% sensitive and 96% specific to delirium on day 1. Positive and Negative Predictive Values were 91% and 100%, respectively. DelApp-ICU scores were responsive to changes in CAM-ICU status., Conclusions: DelApp-ICU shows promise for assessing inattention and delirium in ICU patients, including longitudinally monitoring deficits and providing a metric of delirium severity., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: Language impairment is recognized as as part of the delirium syndrome, yet there is little neuropsychological research on the nature of this dysfunction. Here we hypothesized that patients with delirium show impairments in language formation, coherence and comprehension., Methods: This was a case-control study in 45 hospitalized patients (aged 65-97 years) with delirium, dementia without delirium, or no cognitive impairment (N = 15 per group). DSM-5 criteria were used for delirium. Speech was elicited during (1) structured conversational questioning, and (2) the "Cookie Theft" picture description task. Language comprehension was assessed through standardized verbal and written commands. Interviews were audio-recorded and transcribed., Results: Delirium and dementia groups scored lower on the conversational assessment than the control group (p<0.01, moderate effect sizes (r) of 0.48 and 0.51, resp.). In the Cookie Theft task, the average length of utterances (i.e. unit of speech), indicating language productivity and fluency, distinguished patients with delirium from those with dementia (p<0.01, r = 0.50) and no cognitive impairment (p<0.01, r = 0.55). Patients with delirium performed worse on written comprehension tests compared to cognitively unimpaired patients (p<0.01, r = 0.63), but not compared to the dementia group., Conclusions: Production of spontaneous speech, word quantity, speech content and verbal and written language comprehension are impaired in delirious patients compared to cognitively unimpaired patients. Additionally, patients with delirium produced significantly less fluent speech than those with dementia. These findings have implications for how speech and language are evaluated in delirium assessments, and also for communication with patients with delirium. A study limitation was that the delirium group included patients with co-morbid dementia, which precludes drawing conclusions about the specific language profile of delirium., Competing Interests: The authors have declared that no competing interests exist.

Objective: In recent years, there has been a blossoming of studies examining cerebrospinal fluid (CSF) as a method of studying the pathophysiology of delirium. We systematically reviewed the literature for CSF studies in delirium and provide here a summary of the implications for our understanding of delirium pathophysiology. We also summarise the methods used for CSF analysis and discuss challenges and implications for future studies., Methods: In this systematic review, we screened MEDLINE, EMBASE, PsycINFO, Web of Science, PubMed and the Cochrane Library for articles on CSF biomarkers in delirium, published on 3 September 2016. Studies were required to use Diagnostic and Statistical Manual of Mental Disorders or International Classification of Diseases criteria for delirium or a validated tool. We excluded case reports. There were no other restrictions on study type., Results: We identified 3280 articles from our initial search, and 22 articles were included in this review. All studies were prospective, including over 400 patients with delirium and 700 controls. More than 70 different biomarkers were studied. Studies could not be compared with each other for meta-analysis because of their heterogeneity and varied widely in their risk of bias and quality assessments., Conclusions: The 22 studies identified in this review reveal a small but growing literature, in which many of the important hypotheses in delirium pathogenesis have been examined, but from which few firm conclusions can currently be drawn. Nevertheless, the overall interpretation of the literature supports the vulnerable brain concept, that is, that biomarker evidence of, for example, Alzheimer's disease pathology and/or neuroinflammation, is associated with delirium., (Copyright © 2017 John Wiley & Sons, Ltd.)

[This corrects the article DOI: 10.1016/j.intell.2014.05.006.].

Objective: The diagnosis of delirium depends on eliciting its features through mental status examination and informant history. However, there is marked heterogeneity in how these features are assessed, from binary subjective clinical judgement to more comprehensive methods supported by cognitive testing. The aim of this article is to review the neuropsychological research in delirium and suggest future directions in research and clinical practice., Methods: We reviewed the neuropsychological literature on formal assessment and quantification of the different domains in delirium, focusing on the core feature of inattention., Results: Few studies have characterised and quantified the features of delirium using objective methods commonly employed in neuropsychological research. The existing evidence confirms that patients with delirium usually show impairments on objective tests of attention compared with cognitively intact controls and, in most cases, compared with patients with dementia. Further, abnormal level of arousal appears to be a specific indicator of delirium. The neuropsychological evidence base for impairments in other cognitive domains in delirium, including visual perception, language and thought processes, is small., Conclusions: Delirium diagnosis requires accurate testing for its features, but there is little neuropsychological research examining the nature of these features, or evaluating the reliability, validity and discriminatory power of existing assessment processes. More research using the neuropsychological approach has enormous potential to improve and standardise delirium assessment methods of the individual features of delirium, such as inattention, and in developing more robust reference standards to enable greater comparability between studies., (Copyright © 2017 John Wiley & Sons, Ltd.)

Background: Delirium is a common and serious clinical syndrome which is often missed in routine clinical care. The core cognitive feature is inattention. We developed a novel bedside neuropsychological test for assessing inattention in delirium implemented on a smartphone platform (DelApp). We aim to evaluate the diagnostic performance of the DelApp in a representative cohort of older hospitalised patients., Methods: This is a prospective study of older non-scheduled hospitalised patients (target n = 500, age ≥ 65), recruited from elderly care and acute orthopaedic wards. Exclusion criteria are: non-English speakers; severe vision or hearing impairment; photosensitive epilepsy. A structured reference standard delirium assessment based on DSM-5 criteria will be used, which includes a cognitive test battery administered by a trained assessor (Orientation-Memory-Concentration Test, Abbreviated Mental Test-10, Delirium Rating Severity Scale-Revised-98, digit span, months and days backwards, Vigilance A' test) and assessment of arousal (Observational Scale of Level of Arousal, Richmond Agitation Sedation Scale). Prior change in cognition will be documented using the Informant Questionnaire on Cognitive Decline in the Elderly. Patients will be categorized as delirium (with/without dementia), possible delirium, dementia, no cognitive impairment, or undetermined. A separate assessor (blinded to diagnosis and assessments) will administer the DelApp index test within 3 h of the reference standard assessment. The DelApp comprises assessment of arousal (score 0-4) and sustained attention (score 0-6), yielding a total score between 0 and 10 (higher score = better performance). Outcomes (length of stay, mortality and discharge location) will be collected at 12 weeks. We will evaluate a priori cutpoints derived from a previous case-control study. Measures of the accuracy of DelApp will include sensitivity, specificity, positive and negative predictive values, and area under the ROC curve. We plan repeat assessments on up to 4 occasions in a purposive subsample of 30 patients (15 delirium, 15 no delirium) to examine changes over time., Discussion: This study evaluates the diagnostic test accuracy of a novel smartphone test for delirium in a representative cohort of older hospitalised patients, including those with dementia. DelApp has the potential to be a convenient, objective method of improving delirium assessment for older people in acute care., Trial Registration: Clinical trials.gov, NCT02590796 . Registered on 29 Oct 2015. Protocol version 5, dated 25 July 2016.

Goal: Magnetic resonance imaging (MRI) is the preferred modality for research on structural age-related brain changes. However, computed tomography (CT) is widely available and has practical and cost advantages over MRI for large-scale brain imaging research studies in acutely unwell patients. However, the relationships between MRI and CT measures of white matter hyperintensities (WMH) and atrophy are unclear. We examined the relationships between visual ratings of WMH, atrophy, and old infarcts in patients who had both CT and MRI scans., Materials and Methods: Patients who had both CT and MRI scans in the International Stroke Trial-3 were studied. In both modalities, 2 raters independently completed standardized visual rating scales for WMH, and for central and superficial atrophy using a 5-point scale. In addition, 1 rater recorded old infarcts according to size and location., Findings: Seventy patients with a mean age of 69 years were studied. There were moderate to substantial intrarater CT-MRI agreements for periventricular components of WMH scales (weighted Κappa = .55-.75). Agreements for basal ganglia ratings were lower (weighted Κappa = .18-.44), partly because of the misclassification of prominent perivascular spaces. Atrophy scales showed moderate to substantial CT-MRI agreements (weighted Κappa = .44-.70). MRI was more sensitive in the detection of smaller infarcts and cavitated lesions., Conclusions: Standardized visual rating scales of white matter lesions and atrophy mostly show substantial agreement between CT and MRI. Clinical CT scans have a strong potential for wider exploitation in research studies, particularly in acutely unwell populations., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The Oslo Study of Clonidine in Elderly Patients with Delirium (LUCID) is an RCT investigating the effect of clonidine in medical patients > 65 years with delirium. To assess the dosage regimen and safety measures of this study protocol, we measured the plasma concentrations and hemodynamic effects of clonidine in the first 20 patients., Methods: Patients were randomised to clonidine (n = 10) or placebo (n = 10). The treatment group was given a loading dose (75μg every 3rd hour up to a maximum of 4 doses) to reach steady state, and further 75μg twice daily until delirium free for 2 days, discharge or a maximum of 7 days. Blood pressure (BP) and heart rate (HR) were measured just before every dose. If the systolic BP was < 100 mmHg or HR < 50 beats per minute the next dose was omitted. Plasma concentrations of clonidine were measured 3 h after each drug intake on day 1, just before intake (day 2 and at steady state day 4-6) and 3 h after intake at steady state (C max ). Our estimated pre-specified plasma concentration target range was 0.3-0.7μg/L., Results: 3 h after the first dose of 75μg clonidine, plasma concentration levels rose to median 0.35 (range 0.24-0.40)μg/L. Median trough concentration (C 0 ) at day 2 was 0.70 (0.47-0.96)μg/L. At steady state, median C 0 was 0.47 (0.36-0.76)μg/L, rising to C max 0.74 (0.56-0.95)μg/L 3 h post dose. A significant haemodynamic change from baseline was only found at a few time-points during the loading doses within the clonidine group. There was however extensive individual BP and HR variation in both the clonidine and placebo groups, and when comparing the change scores (delta values) between the clonidine and the placebo groups, there were no significant differences., Conclusions: The plasma concentration of clonidine was at the higher end of the estimated therapeutic range. Hemodynamic changes during clonidine treatment were as expected, with trends towards lower blood pressure and heart rate in patients treated with clonidine, but with dose adjustments based on SBP this protocol appears safe., Trial Registration: ClinicalTrials.gov NCT01956604 , 09.25.2013. EudraCT Number: 2013-000815-26, 03.18.2013. Enrolment of first participant: 04.24.2014.

Background/objectives: Stroke is a leading cause of disability worldwide, and a significant proportion of stroke survivors require long-term institutional care. Understanding who cannot be discharged home is important for health and social care planning. Our aim was to establish predictive factors for discharge to institutional care after hospitalization for stroke., Design: We registered and conducted a systematic review and meta-analysis (PROSPERO: CRD42015023497) of observational studies. We searched MEDLINE, EMBASE, and CINAHL Plus to February 2017. Quantitative synthesis was performed where data allowed., Setting: Acute and rehabilitation hospitals., Participants: Adults hospitalized for stroke who were newly admitted directly to long-term institutional care at the time of hospital discharge., Measurements: Factors associated with new institutionalization., Results: From 10,420 records, we included 18 studies (n = 32,139 participants). The studies were heterogeneous and conducted in Europe, North America, and East Asia. Eight studies were at high risk of selection bias. The proportion of those surviving to discharge who were newly discharged to long-term care varied from 7% to 39% (median 17%, interquartile range 12%), and the model of care received in the long-term care setting was not defined. Older age and greater stroke severity had a consistently positive association with the need for long-term care admission. Individuals who had a severe stroke were 26 times as likely to be admitted to long-term care than those who had a minor stroke. Individuals aged 65 and older had a risk of stroke that was three times as great as that of younger individuals. Potentially modifiable factors were rarely examined., Conclusion: Age and stroke severity are important predictors of institutional long-term care admission directly from the hospital after an acute stroke. Potentially modifiable factors should be the target of future research. Stroke outcome studies should report discharge destination, defining the model of care provided in the long-term care setting., (© 2017 The Authors. Journal of the American Geriatrics Society published by Wiley Periodicals, Inc. on behalf of The American Geriatrics Society.)

Background: Reduced level of arousal is commonly observed in medical admissions and may predict in-hospital mortality. Delirium and reduced level of arousal are closely related. We systematically reviewed and conducted a meta-analysis of studies in adult acute medical patients of the relationship between reduced level of arousal on admission and in-hospital mortality., Methods: We conducted a systematic review (PROSPERO: CRD42016022048), searching MEDLINE and EMBASE. We included studies of adult patients admitted with acute medical illness with level of arousal assessed on admission and mortality rates reported. We performed meta-analysis using a random effects model., Results: From 23,941 studies we included 21 with 14 included in the meta-analysis. Mean age range was 33.4 - 83.8 years. Studies considered unselected general medical admissions (8 studies, n=13,039) or specific medical conditions (13 studies, n=38,882). Methods of evaluating level of arousal varied. The prevalence of reduced level of arousal was 3.1%-76.9% (median 13.5%). Mortality rates were 1.7%-58% (median 15.9%). Reduced level of arousal was associated with higher in-hospital mortality (pooled OR 5.71; 95% CI 4.21-7.74; low quality evidence: high risk of bias, clinical heterogeneity and possible publication bias)., Conclusions: Reduced level of arousal on hospital admission may be a strong predictor of in-hospital mortality. Most evidence was of low quality. Reduced level of arousal is highly specific to delirium, better formal detection of hypoactive delirium and implementation of care pathways may improve outcomes. Future studies to assess the impact of interventions on in-hospital mortality should use validated assessments of both level of arousal and delirium.

Elevated cortisol levels have been hypothesized to contribute to cognitive aging, but study findings are inconsistent. In the present study, we examined the association between salivary cortisol in older age and cognitive ability across the life course. We used data from 370 members of the 36-Day Sample of the Scottish Mental Survey 1947, who underwent cognitive testing at age 11 years and were then followed up at around age 78 years, completing further cognitive tests and providing diurnal salivary cortisol samples. We hypothesized that higher cortisol levels would be associated with lower cognitive ability in older age and greater cognitive decline from childhood to older age but also lower childhood cognitive ability. Few of the tested associations were significant, and of those that were, most suggested a positive relationship between cortisol and cognitive ability. Only 1 cognitive measure showed any sign of cortisol-related impairment. However, after correcting for multiple comparisons, no results remained significant. These findings suggest that cortisol may not play an important role in cognitive aging across the life course., (Copyright © 2017. Published by Elsevier Inc.)

Background: Detecting delirium superimposed on dementia (DSD) can be challenging because assessment partly relies on cognitive tests that may be abnormal in both conditions. We hypothesized that a combined arousal and attention testing procedure would accurately detect DSD., Methods: Patients aged ≥70 years were recruited from five hospitals across Europe. Delirium was diagnosed by physicians using DSM-5 criteria using information from nurses, carers, and medical records. Dementia was ascertained by the Informant Questionnaire on Cognitive Decline in the Elderly. Arousal was measured using the Observational Scale of Level of Arousal (OSLA), which assesses eye opening, eye contact, posture, movement, and communication. Attention was measured by participants signaling each time an "A" was heard when "S-A-V-E-A-H-A-A-R-T" was read out., Results: The sample included 114 persons (mean age 82 years (SD 7); 54% women). Dementia alone was present in 25% (n = 28), delirium alone in 18% (n = 21), DSD in 27% (n = 31), and neither in 30% (n = 34). Arousal and attention was assessed in n = 109 (96%). Using OSLA, 83% participants were correctly identified as having delirium (sensitivity 85%, specificity 82%, AUROC 0.92). The attention task correctly classified 76% of participants with delirium (sensitivity 90%, specificity 64%, AUROC 0.80). Combining scores correctly classified 91% of participants with delirium (sensitivity 84%, specificity 92%, AUROC 0.94). Diagnostic accuracy remained high in the subgroup with dementia (93% correctly classified, sensitivity 94%, specificity 92%, AUROC 0.98)., Conclusions: This combined arousal-attention assessment to detect DSD was brief yet had high diagnostic accuracy. Such an approach could have clinical utility for diagnosing DSD.

Delirium is an acute and usually transient severe neuropsychiatric syndrome associated with significant long-term physical morbidity. However, its chronic psychiatric sequelae remain poorly characterized. To investigate the prevalence of psychiatric symptoms, namely anxiety, depressive, and post-traumatic stress disorder (PTSD) symptoms after delirium, a systematic literature search of MEDLINE, EMBASE and PsycINFO databases was performed independently by two authors in March 2016. Bibliographies were hand-searched, and a forward- and backward-citation search using Web of Science was performed for all included studies. Of 6411 titles, we included eight prospective cohort studies, including 370 patients with delirium and 1073 without delirium. Studies were heterogeneous and mostly included older people from a range of clinical groups. Consideration of confounders was variable. The prevalence of depressive symptoms was almost three times higher in patients with delirium than in patients without delirium (22.2% vs 8.0%, risk ratio = 2.79; 95% confidence interval = 1.36-5.73). There was no statistically significant difference between the prevalence of anxiety symptoms between patients with and without delirium. The prevalence of PTSD symptoms after delirium was inconclusive: only one study investigated this and no association between PTSD symptoms after delirium was reported. There is limited published evidence of the prevalence of psychiatric symptoms after non-ICU delirium and the strongest evidence is for depressive symptoms. Further longitudinal studies are warranted to investigate the prevalence of anxiety and PTSD symptoms., (© 2017 Japanese Psychogeriatric Society.)

Delirium is a common and serious psychiatric syndrome caused by an underlying medical condition. It is associated with significant mortality and increased healthcare resource utilization. There are few biological markers of delirium, perhaps related to the etiologic heterogeneity of the syndrome. Functional near-infrared spectroscopy (fNIRS) is an optical topography system to measure changes in the concentration of oxygenated hemoglobin ([oxy-Hb]) in the cerebral cortex. We examined whether altered cortical brain activity in delirious patients with end stage liver disease (ESLD) is detected by fNIRS. We found that the [oxy-Hb] change during the verbal fluency task (VFT) was reduced in patients with ESLD compared with healthy controls (HC) in the prefrontal and bi-temporal regions. The [oxy-Hb] change during the sustained attention task (SAT) was elevated in patients with ESLD compared to HC in the prefrontal and left temporal regions. Notably, [oxy-Hb] change in the left dorsolateral prefrontal cortex during SAT showed a positive correlation with the severity of delirium. Our results suggest that [oxy-Hb] change in the prefrontal cortex during the sustained attention task measured with fNIRS might serve as a biological marker associated with delirium in ESLD patients.

Objectives: Delirium in the ICU is associated with poor outcomes but is under-detected. Here we evaluated performance of a novel, graded test for objectively detecting inattention in delirium, implemented on a custom-built computerized device (Edinburgh Delirium Test Box-ICU)., Design: A pilot study was conducted, followed by a prospective case-control study., Setting: Royal Infirmary of Edinburgh General ICU., Patients: A pilot study was conducted in an opportunistic sample of 20 patients. This was followed by a validation study in 30 selected patients with and without delirium (median age, 63 yr; range, 23-84) who were assessed with the Edinburgh Delirium Test Box-ICU on up to 5 separate days. Presence of delirium was assessed using the Confusion Assessment Method for the ICU., Measurements and Main Results: The Edinburgh Delirium Test Box-ICU involves a behavioral assessment and a computerized test of attention, requiring patients to count slowly presented lights. Thirty patients were assessed a total of 79 times (n = 31, 23, 15, 8, and 2 for subsequent assessments; 38% delirious). Edinburgh Delirium Test Box-ICU scores (range, 0-11) were lower for patients with delirium than those without at the first (median, 0 vs 9.5), second (median, 3.5 vs 9), and third (median, 0 vs 10.5) assessments (all p < 0.001). An Edinburgh Delirium Test Box-ICU score less than or equal to 5 was 100% sensitive and 92% specific to delirium across assessments. Longitudinally, participants' Edinburgh Delirium Test Box-ICU performance was associated with delirium status., Conclusions: These findings suggest that the Edinburgh Delirium Test Box-ICU has diagnostic utility in detecting ICU delirium in patients with Richmond Agitation and Sedation Scale Score greater than -3. The Edinburgh Delirium Test Box-ICU has potential additional value in longitudinally tracking attentional deficits because it provides a range of scores and is sensitive to change.

Background: moving into long-term institutional care is a significant life event for any individual. Predictors of institutional care admission from community-dwellers and people with dementia have been described, but those from the acute hospital setting have not been systematically reviewed. Our aim was to establish predictive factors for discharge to institutional care following acute hospitalisation., Methods: we registered and conducted a systematic review (PROSPERO: CRD42015023497). We searched MEDLINE; EMBASE and CINAHL Plus in September 2015. We included observational studies of patients admitted directly to long-term institutional care following acute hospitalisation where factors associated with institutionalisation were reported., Results: from 9,176 records, we included 23 studies (n = 354,985 participants). Studies were heterogeneous, with the proportions discharged to a care home 3-77% (median 15%). Eleven studies (n = 12,642), of moderate to low quality, were included in the quantitative synthesis. The need for institutional long-term care was associated with age (pooled odds ratio (OR) 1.02, 95% confidence intervals (CI): 1.00-1.04), female sex (pooled OR 1.41, 95% CI: 1.03-1.92), dementia (pooled OR 2.14, 95% CI: 1.24-3.70) and functional dependency (pooled OR 2.06, 95% CI: 1.58-2.69)., Conclusions: discharge to long-term institutional care following acute hospitalisation is common, but current data do not allow prediction of who will make this transition. Potentially important predictors evaluated in community cohorts have not been examined in hospitalised cohorts. Understanding these predictors could help identify individuals at risk early in their admission, and support them in this transition or potentially intervene to reduce their risk., (© The Author 2017. Published by Oxford University Press on behalf of the British Geriatrics Society.)

High, unabated glucocorticoid (GC) levels are thought to selectively damage certain tissue types. The hippocampus is thought to be particularly susceptible to such effects, and though findings from animal models and human patients provide some support for this hypothesis, evidence for associations between elevated GCs and lower hippocampal volumes in older age (when GC levels are at greater risk of dysregulation) is inconclusive. To address the possibility that the effects of GCs in non-pathological ageing may be too subtle for gross volumetry to reliably detect, we analyse associations between salivary cortisol (diurnal and reactive measures), hippocampal morphology and diffusion characteristics in 88 males, aged ∼73 years. However, our results provide only weak support for this hypothesis. Though nominally significant peaks in morphology were found in both hippocampi across all salivary cortisol measures (standardised β magnitudes<0.518, p uncorrected >0.0000003), associations were both positive and negative, and none survived false discovery rate correction. We found one single significant association (out of 12 comparisons) between a general measure of hippocampal diffusion and reactive cortisol slope (β=0.290, p=0.008) which appeared to be driven predominantly by mean diffusivity but did not survive correction for multiple testing. The current data therefore do not clearly support the hypothesis that elevated cortisol levels are associated with subtle variations in hippocampal shape or microstructure in non-pathological older age., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Delirium is a profound neuropsychiatric disturbance precipitated by acute illness. Although dementia is the major risk factor this has typically been considered a binary quantity (i.e., cognitively impaired versus cognitively normal) with respect to delirium risk. We used humans and mice to address the hypothesis that the severity of underlying neurodegenerative changes and/or cognitive impairment progressively alters delirium risk., Methods: Humans in a population-based longitudinal study, Vantaa 85+, were followed for incident delirium. Odds for reporting delirium at follow-up (outcome) were modeled using random-effects logistic regression, where prior cognitive impairment measured by Mini-Mental State Exam (MMSE) (exposure) was considered. To address whether underlying neurodegenerative pathology increased susceptibility to acute cognitive change, mice at three stages of neurodegenerative disease progression (ME7 model of neurodegeneration: controls, 12 weeks, and 16 weeks) were assessed for acute cognitive dysfunction upon systemic inflammation induced by bacterial lipopolysaccharide (LPS; 100 μg/kg). Synaptic and axonal correlates of susceptibility to acute dysfunction were assessed using immunohistochemistry., Results: In the Vantaa cohort, 465 persons (88.4 ± 2.8 years) completed MMSE at baseline. For every MMSE point lost, risk of incident delirium increased by 5% (p = 0.02). LPS precipitated severe and fluctuating cognitive deficits in 16-week ME7 mice but lower incidence or no deficits in 12-week ME7 and controls, respectively. This was associated with progressive thalamic synaptic loss and axonal pathology., Conclusion: A human population-based cohort with graded severity of existing cognitive impairment and a mouse model with progressing neurodegeneration both indicate that the risk of delirium increases with greater severity of pre-existing cognitive impairment and neuropathology., (Copyright © 2015 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)