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.

Clostridioides difficile infection in neurosurgical patients in a national centre over 10 years: less common but associated with longer hospital stays.

BACKGROUND: Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated (HA) diarrhoea, contributing to patient morbidity and prolonged length-of-stay (LOS). We retrospectively assessed CDI over a decade in a national neurosurgical centre, with a multi-disciplinary approach to CDI surveillance and antimicrobial stewardship, by comparing CDI patients with other patient groups. METHODS: Data on CDI in neurosurgical inpatients between January 2012 and December 2021 were collated. Disease-specific variables were compared to other inpatients with CDI. Rates per 10,000 bed days used were calculated. Patient-specific differences were compared with neurosurgical patients without CDI. CDI rates by patient group were explored using odds ratio (OR) and χ2 analyses. Negative binomial regression was used to investigate CDI rates over time. RESULTS: Of 50 neurosurgical patients with CDI, all were HA; the average age was 53 years (standard deviation (SD) 16.3 years), 49 were first-episode CDI, and three had severe CDI. The majority (76.7%) had received recent antimicrobials. Compared with non-neurosurgical CDI patients, neurosurgical CDI rates differed significantly (1.9 versus 3.6 per 10,000 bed days used, p < 0.05), neurosurgical patients were younger (p ≤ 0.01), C. difficile testing was more likely to be requested by neurosurgeons (OR 2.4; p ≤ 0.01), and the proportion of severe CDI was higher (6% versus 2%, OR 3.0, p = 0.07, confidence interval (CI) 0.54 to 11.3). Within the neurosurgical cohort, CDI patients had an average LOS four times that of other patients (CI 15.2 to 35.1; p < 0.01) and were older (53.5 versus 47.8 years, CI 0.1 to 11 years; p < 0.05). Only one CDI outbreak was linked to neurosurgical patients. CONCLUSION: CDI in neurosurgery patients differed from the wider hospital, with greater awareness of CDI testing. Longer LOS impacted bed utilisation with limited capacity. Robust surveillance supports proactive antimicrobial stewardship programmes in this vulnerable population.

A systematic review and meta-analysis of the accuracy of the clock drawing test (CDT) in the identification of delirium in older hospitalised patients.

Objective: Delirium is a common neurocognitive syndrome among hospitalised older adults. The clock drawing test (CDT) is a relatively simple bedside test of cognitive function. This systematic review and meta-analysis examine the accuracy of the CDT in identifying delirium in hospitalised older adults.Methods: PRISMA guidelines were used to report the identified studies. Pubmed, SCOPUS, and Ovid and EBSCO platforms (including MEDLINE ®, PsycINFO, PsycEXTRA, EMCARE, CINAHL and EMBASE databases) were searched. Studies were assessed for methodological quality using the Downs and Black Tool. Data were extracted regarding the number of delirious/not delirious, number with normal and abnormal CDT, age, and MMSE scores, and information regarding CDT scoring, criteria for diagnosis of delirium and setting of the study. Analysis was carried out with the "Mada" and "Metatron" packages of R software.Results: Fifteen studies were examined. The number of participants was 2199, of whom 597 (27.15%) were diagnosed with delirium. The overall sensitivity of CDT in the absence of any formal cognitive test was 0.76 (0.58-0.87) with specificity of 0.70 (0.51-0.83). When the MMSE was taken into account, the specificity and sensitivity reduced to 0.51. Diagnostic criteria for delirium, scoring method of CDT, age of participants and setting significantly (p < 0.05) affect the sensitivity and specificity of the CDT.Conclusion: Although, the CDT is generally considered to be a simple and easy to administer screening tool for cognitive impairment in older hospitalised adults, when a more formal cognitive test is used its sensitivity and specificity to detect delirium is low.

Delirium Phenotype by Age and Sex in a Pooled Data Set of Adult Patients.

The authors aimed to evaluate whether the clinical phenotype of delirium differs if dichotomized either by sex or age (cutoff age, 65 years old) in a pooled sample of 406 nondemented adult patients with delirium as defined by DSM-IV criteria. Delirium characteristics were measured with the Delirium Rating Scale-Revised-98 (DRS-R-98). DRS-R-98 items were subgrouped to represent subscores representing the three core domains of delirium (cognitive, higher-order thinking, and circadian), noncore accessory symptoms (psychotic and affective), and diagnostic characteristics (temporal onset, fluctuation, and physical disorder). The authors compared means of the DRS-R-98 subscores and medians of individual items. Exploratory factor analyses evaluated delirium characteristics for each subgroup for each of the four groups-male, female, nongeriatric, and geriatric-while taking into account active medical diagnoses. Males had higher scores on motor agitation and affective lability (behavioral), whereas females had a higher frequency of hypoactive delirium. Delirium had a two-factor structure that emerged in all four study groups, and all its core domains loaded (i.e., correlated together) onto some of these two factors and with circadian domain correlating with accessory symptoms. Although the influence of a variety of active diagnoses on delirium was small and complex, traumatic brain injury had a clear influence on cognitive domain and abrupt onset. Age had a mild influence over delirium characteristics for both males and females. In conclusion, the authors confirmed a two-factor structure for delirium phenomenology, regardless of age and sex, with few significant differences between etiological groups.

Attention, vigilance, and visuospatial function in hospitalized elderly medical patients: relationship to delirium syndromal status and motor subtype profile.

ABSTRACTBackground:The early and effective detection of neurocognitive disorders poses a key diagnostic challenge. We examined performance on common cognitive bedside tests according to differing delirium syndromal status and clinical (motor) subtypes in hospitalized elderly medical inpatients. METHODS: A battery of nine bedside cognitive tests was performed on elderly medical inpatients with DSM-IV delirium, subsyndromal delirium (SSD), and no delirium (ND). Patients with delirium were compared according to clinical (motor) subtypes. RESULTS: A total of 198 patients (mean age 79.14 ± 8.26) were assessed with full syndromal delirium (FSD: n = 110), SSD (n = 45), and ND (n = 43). Delirium status was not associated with differences in terms of gender distribution, age, or overall medication use. Dementia burden increased with greater delirium status. Overall, the ability to meaningfully engage with the tests varied from 59% for the Vigilance B test to 85% for Spatial Span Forward test and was lowest in patients with FSD, where engagement ranged from 32% for the Vigilance B test to 77% for the Spatial Span Forwards test. The ND group was distinguished from SSD group for the Months of the year backwards, Vigilance B, global VSP, Clock Drawing test, and Interlocking Pentagons test. The SSD group was distinguished from the FSD group by Vigilance A, Spatial Span Forward, and Spatial Span Backwards. Regarding differences among motor subtypes in terms of percentage engagement and performance, the No subtype group had higher ratings across all tests. Delirious patients with no subtype had significantly lower scores on the DRS-R98 than for the other three subtype categories. CONCLUSIONS: Simple bedside tests of attention, vigilance, and visuospatial ability are useful in distinguishing neurocognitive disorders, including SSD from other presentations.

Confirmatory Factor Analysis of the Delirium Rating Scale Revised-98 (DRS-R98).

Principal components analysis applied to the Delirium Rating Scale-Revised-98 contributes to understanding the delirium construct. Using a multisite pooled international delirium database, the authors applied confirmatory factor analysis to Delirium Rating Scale-Revised-98 scores from 859 adult patients evaluated by delirium experts (delirium, N=516; nondelirium, N=343). Confirmatory factor analysis found all diagnostic features and core symptoms (cognitive, language, thought process, sleep-wake cycle, motor retardation), except motor agitation, loaded onto factor 1. Motor agitation loaded onto factor 2 with noncore symptoms (delusions, affective lability, and perceptual disturbances). Factor 1 loading supports delirium as a single construct, but when accompanied by psychosis, motor agitation's role may not be solely as a circadian activity indicator.

A longitudinal study of delirium phenomenology indicates widespread neural dysfunction.

OBJECTIVES: Delirium affects all higher cortical functions supporting complex information processing consistent with widespread neural network impairment. We evaluated the relative prominence of delirium symptoms throughout episodes to assess whether impaired consciousness is selectively affecting certain brain functions at different timepoints. METHODS: Twice-weekly assessments of 100 consecutive patients with DSM-IV delirium in a palliative care unit used the Delirium Rating Scale Revised-98 (DRS-R98) and Cognitive Test for Delirium (CTD). A mixed-effects model was employed to estimate changes in severity of individual symptoms over time. RESULTS: Mean age = 7 0.2 ± 10.5 years, 51% were male, and 27 had a comorbid dementia. A total of 323 assessments (range 2-9 per case) were conducted, but up to 6 are reported herein. Frequency and severity of individual DRS-R98 symptoms was very consistent over time even though the majority of patients (80%) experienced fluctuation in symptom severity over the course of hours or minutes. Over time, DRS-R98 items for attention (88-100%), sleep-wake cycle disturbance (90-100%), and any motor disturbance (87-100%), and CTD attention and vigilance were most frequently and consistently impaired. Mixed-effects regression modeling identified only very small magnitudes of change in individual symptoms over time, including the three core domains. SIGNIFICANCE OF RESULTS: Attention is disproportionately impaired during the entire episode of delirium, consistent with thalamic dysfunction underlying both an impaired state of consciousness and well-known EEG slowing. All individual symptoms and three core domains remain relatively stable despite small fluctuations in symptom severity for a given day, which supports a consistent state of impaired higher cortical functions throughout an episode of delirium.

A comparison of the revised Delirium Rating Scale (DRS-R98) and the Memorial Delirium Assessment Scale (MDAS) in a palliative care cohort with DSM-IV delirium.

OBJECTIVE: Assessment of delirium is performed with a variety of instruments, making comparisons between studies difficult. A conversion rule between commonly used instruments would aid such comparisons. The present study aimed to compare the revised Delirium Rating Scale (DRS-R98) and Memorial Delirium Assessment Scale (MDAS) in a palliative care population and derive conversion rules between the two scales. METHOD: Both instruments were employed to assess 77 consecutive patients with DSM-IV delirium, and the measures were repeated at three-day intervals. Conversion rules were derived from the data at initial assessment and tested on subsequent data. RESULTS: There was substantial overall agreement between the two scales [concordance correlation coefficient (CCC) = 0.70 (CI 95 = 0.60-0.78)] and between most common items (weighted κ ranging from 0.63 to 0.86). Although the two scales overlap considerably, there were some subtle differences with only modest agreement between the attention (weighted κ = 0.42) and thought process (weighted κ = 0.61) items. The conversion rule from total MDAS score to DRS-R98 severity scores demonstrated an almost perfect level of agreement (r = 0.86, CCC = 0.86; CI 95 = 0.79-0.91), similar to the conversion rule from DRS-R98 to MDAS. SIGNIFICANCE OF RESULTS: Overall, the derived conversion rules demonstrated promising accuracy in this palliative care population, but further testing in other populations is certainly needed.

Concordance between DSM-IV and DSM-5 criteria for delirium diagnosis in a pooled database of 768 prospectively evaluated patients using the delirium rating scale-revised-98.

BACKGROUND: The Diagnostic and Statistical Manual fifth edition (DSM-5) provides new criteria for delirium diagnosis. We examined delirium diagnosis using these new criteria compared with the Diagnostic and Statistical Manual fourth edition (DSM-IV) in a large dataset of patients assessed for delirium and related presentations. METHODS: Patient data (n = 768) from six prospectively collected cohorts, clinically assessed using DSM-IV and the Delirium Rating Scale-Revised-98 (DRS-R98), were pooled. Post hoc application of DRS-R98 item scores were used to rate DSM-5 criteria. 'Strict' and 'relaxed' DSM-5 criteria to ascertain delirium were compared to rates determined by DSM-IV. RESULTS: Using DSM-IV by clinical assessment, delirium was found in 510/768 patients (66%). Strict DSM-5 criteria categorized 158 as delirious including 155 (30%) with DSM-IV delirium, whereas relaxed DSM-5 criteria identified 466 as delirious, including 455 (89%) diagnosed by DSM-IV (P <0.001). The concordance between the different diagnostic methods was: 53% (ĸ = 0.22) between DSM-IV and the strict DSM-5, 91% (ĸ = 0.82) between the DSM-IV and relaxed DSM-5 criteria and 60% (ĸ = 0.29) between the strict versus relaxed DSM-5 criteria. Only 155 cases were identified as delirium by all three approaches. The 55 (11%) patients with DSM-IV delirium who were not rated as delirious by relaxed criteria had lower mean DRS-R98 total scores than those rated as delirious (13.7 ± 3.9 versus 23.7 ± 6.0; P <0.001). Conversely, mean DRS-R98 score (21.1 ± 6.4) for the 70% not rated as delirious by strict DSM-5 criteria was consistent with suggested cutoff scores for full syndromal delirium. Only 11 cases met DSM-5 criteria that were not deemed to have DSM-IV delirium. CONCLUSIONS: The concordance between DSM-IV and the new DSM-5 delirium criteria varies considerably depending on the interpretation of criteria. Overly-strict adherence for some new text details in DSM-5 criteria would reduce the number of delirium cases diagnosed; however, a more 'relaxed' approach renders DSM-5 criteria comparable to DSM-IV with minimal impact on their actual application and is thus recommended.

Attention! A good bedside test for delirium?

BACKGROUND: Routine delirium screening could improve delirium detection, but it remains unclear as to which screening tool is most suitable. We tested the diagnostic accuracy of the following screening methods (either individually or in combination) in the detection of delirium: MOTYB (months of the year backwards); SSF (Spatial Span Forwards); evidence of subjective or objective 'confusion'. METHODS: We performed a cross-sectional study of general hospital adult inpatients in a large tertiary referral hospital. Screening tests were performed by junior medical trainees. Subsequently, two independent formal delirium assessments were performed: first, the Confusion Assessment Method (CAM) followed by the Delirium Rating Scale-Revised 98 (DRS-R98). DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, fourth edition) criteria were used to assign delirium diagnosis. Sensitivity and specificity ratios with 95% CIs were calculated for each screening method. RESULTS: 265 patients were included. The most precise screening method overall was achieved by simultaneously performing MOTYB and assessing for subjective/objective confusion (sensitivity 93.8%, 95% CI 82.8 to 98.6; specificity 84.7%, 95% CI 79.2 to 89.2). In older patients, MOTYB alone was most accurate, whereas in younger patients, a simultaneous combination of SSF (cut-off 4) with either MOTYB or assessment of subjective/objective confusion was best. In every case, addition of the CAM as a second-line screening step to improve specificity resulted in considerable loss in sensitivity. CONCLUSIONS: Our results suggest that simple attention tests may be useful in delirium screening. MOTYB used alone was the most accurate screening test in older people.

What do we really know about the treatment of delirium with antipsychotics? Ten key issues for delirium pharmacotherapy.

Despite the significant burden of delirium among hospitalized adults, no pharmacologic intervention is approved for delirium treatment. Antipsychotic agents are the best studied but there are uncertainties as to how these agents can be optimally applied in everyday practice. We searched Medline and PubMed databases for publications from 1980 to April 2012 to identify studies of delirium treatment with antipsychotic agents. Studies of primary prevention using pharmacotherapy were not included. We identified 28 prospective studies that met our inclusion criteria, of which 15 were comparison studies (11 randomized), 2 of which were placebo-controlled. The quality of comparison studies was assessed using the Jadad scale. The DRS (N = 12) and DRS-R98 (N = 9) were the most commonly used instruments for measuring responsiveness. These studies suggest that around 75% of delirious patients who receive short-term treatment with low-dose antipsychotics experience clinical response. Response rates appear quite consistent across different patient groups and treatment settings. Studies do not suggest significant differences in efficacy for haloperidol versus atypical agents, but report higher rates of extrapyramidal side effects with haloperidol. Comorbid dementia may be associated with reduced response rates but this requires further study. The available evidence does not indicate major differences in response rates between clinical subtypes of delirium. The extent to which therapeutic effects can be explained by alleviation of specific symptoms (e.g. sleep or behavioral disturbances) versus a syndromal effect that encompasses both cognitive and noncognitive symptoms of delirium is not known. Future research needs to explore the relationship between therapeutic effects and changes in pathophysiological markers of delirium. Less than half of reports were rated as reasonable quality evidence on the Jadad scale, highlighting the need for future studies of better quality design, and in particular incorporating placebo-controlled work.

Three core domains of delirium validated using exploratory and confirmatory factor analyses.

OBJECTIVE: To confirm the existence of the proposed three-core symptom domains in delirium by analyzing a dataset of nondemented adults using selected core symptoms as measured by the Delirium Rating Scale-Revised-98 (DRS-R98) scale. METHODS: Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) of proposed delirium core symptoms were conducted in a pooled international dataset of 592 delirious and nondelirious patients using DSM-IV criteria from 14 studies with comparable methodologies. Using DRS-R98 categorization, 445 had either subsyndromal or full delirium and comprised the delirium group. The dataset was divided into three independent random subsamples to perform a stepwise analysis. First we performed EFA in 100 cases to delineate latent factor loadings of DRS-R98 items selected to represent the three-core domains (circadian, higher level thinking, and cognitive). These items were then assessed using CFA-modeling (n = 246) followed by a CFA-validation (n = 246). Reliability and goodness of fit of these two CFA were assessed statistically. RESULTS: DRS-R98 items representing the proposed delirium core symptoms loaded onto one factor in the EFA, supporting their core nature. The two CFA confirmed the nature of this core factor as comprising three core domains where DRS-R98 items each loaded with high values (>0.7) onto their corresponding core domain (circadian, higher level thinking, and cognitive) with good fit and reliability. Attention was DRS-R98 item with the highest loading in CFA, followed by thought process, and then by sleep-wake cycle and motor behavior. CONCLUSIONS: Our EFA and CFA confirm and validate the proposed three-core domains of delirium, where symptoms were highly related to the domain that they were hypothesized to represent. These domains are consistent with delirium being a state of impaired consciousness, and should be considered necessary to assess whether in clinical or research settings.

Features of subsyndromal and persistent delirium.

BACKGROUND: Longitudinal studies of delirium phenomenology are lacking. AIMS: We studied features that characterise subsyndromal delirium and persistent delirium over time. METHOD: Twice-weekly evaluations of 100 adults with DSM-IV delirium using the Delirium Rating Scale-Revised-98 (DRS-R98) and Cognitive Test for Delirium (CTD). The generalised estimating equation method identified symptom patterns distinguishing full syndromal from subsyndromal delirium and resolving from persistent delirium. RESULTS: Participants (mean age 70.2 years (s.d. = 10.5)) underwent 323 assessments (range 2-9). Full syndromal delirium was significantly more severe than subsyndromal delirium for DRS-R98 thought process abnormalities, delusions, hallucinations, agitation, retardation, orientation, attention, and short- and long-term memory items, and CTD attention, vigilance, orientation and memory. Persistent full syndromal delirium had greater disturbance of DRS-R98 thought process abnormalities, delusions, agitation, orientation, attention, and short- and long-term memory items, and CTD attention, vigilance and orientation. CONCLUSIONS: Full syndromal delirium differs from subsyndromal delirium over time by greater severity of many cognitive and non-cognitive symptoms. Persistent delirium involves increasing prominence of recognised core diagnostic features and cognitive impairment.

Phenomenological and neuropsychological profile across motor variants of delirium in a palliative-care unit.

Studies using composite measurement of cognition suggest that cognitive performance is similar across motor variants of delirium. The authors assessed neuropsychological and symptom profiles in 100 consecutive cases of DSM-IV delirium allocated to motor subtypes in a palliative-care unit: Hypoactive (N=33), Hyperactive (N=18), Mixed (N=26), and No-Alteration motor groups (N=23). The Mixed group had more severe delirium, with highest scores for DRS-R-98 sleep-wake cycle disturbance, hallucinations, delusions, and language abnormalities. Neither the total Cognitive Test for Delirium nor its five neuropsychological domains differed across Hyperactive, Mixed, and Hypoactive motor groups. Most patients (70%) with no motor alteration had DRS-R-98 scores in the mild or subsyndromal range even though they met DSM-IV criteria. Motor variants in delirium have similar cognitive profiles, but mixed cases differ in expression of several noncognitive features.

Neuropsychiatric and cognitive profile of patients with DSM-IV delirium referred to an old age psychiatry consultation-liaison service.

BACKGROUND: The phenomenology of delirium is understudied, including how the symptom profile varies across populations. The aim of this study was to explore phenomenology occurring in patients with delirium referred to an old age psychiatry consultation-liaison setting and compare with delirium occurring in palliative care patients. METHODS: Consecutive cases of DSM-IV delirium were assessed with the Delirium Rating scale Revised-98 (DRS-R98) and Cognitive Test for Delirium (CTD). RESULTS: Eighty patients (mean age 79.3 ± 7.7 years; mean DRS-R98 total score 21.7 ± 4.9 and total CTD score 10.2 ± 6.3) were included. Forty patients (50%) with comorbid dementia were older, had a longer duration of symptoms at referral, and more severe delirium due to greater cognitive impairments. Inattention (100%) was the most prominent cognitive disturbance, while sleep-wake cycle disturbance (98%), altered motor activity (97%), and thought process abnormality (96%) were the most frequent DRS-R98 non-cognitive features. Inattention was associated with severity of other cognitive disturbances on both the DRS-R98 and CTD, but not with DRS-R98 non-cognitive items. The phenomenological profile was similar to palliative care but with more severe delirium due to greater cognitive and non-cognitive disturbance. CONCLUSION: Delirium is a complex neuropsychiatric syndrome with generalized cognitive impairment and disproportionate inattention. Sleep-wake cycle and motor-activity disturbances are also common. Comorbid dementia results in a similar phenomenological pattern but with greater cognitive impairment and later referral.

How do delirium motor subtypes differ in phenomenology and contributory aetiology? a cross-sectional, multisite study of liaison psychiatry and palliative care patients.

OBJECTIVES: To investigate whether delirium motor subtypes differ in terms of phenomenology and contributory aetiology. DESIGN: Cross-sectional study. SETTING: International study incorporating data from Ireland and India across palliative care, old age liaison psychiatry and general adult liaison psychiatry settings. PARTICIPANTS: 1757 patients diagnosed with delirium using criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fourth edition (DSM IV). PRIMARY AND SECONDARY OUTCOME MEASURES: Hyperactive, mixed and hypoactive delirium subtypes were identified using the abbreviated version of the Delirium Motor Subtype Scale. Phenomenology was assessed using the Delirium Rating Scale Revised. Contributory aetiologies were assessed using the Delirium Aetiology Checklist (DEC), with a score >2 indicating that the aetiology was likely or definitely contributory. RESULTS: Hypoactive delirium was associated with dementia, cerebrovascular and systemic infection aetiologies (p<0.001) and had a lower overall burden of delirium symptoms than the other motor subtypes. Hyperactive delirium was associated with younger age, drug withdrawal and the DEC category other systemic aetiologies (p<0.001). Mixed delirium showed the greatest symptom burden and was more often associated with drug intoxication and metabolic disturbance (p<0.001). All three delirium motor subtypes had similar levels of impairment in attention and visuospatial functioning but differed significantly when compared with no subtype (p<0.001). CONCLUSIONS: This study indicates a pattern of aetiology and symptomatology of delirium motor subtypes across a large international sample that had previously been lacking. It serves to improve our understanding of this complex condition and has implications in terms of early detection and management of delirium.

A comparison of neuropsychiatric and cognitive profiles in delirium, dementia, comorbid delirium-dementia and cognitively intact controls.

PURPOSE: Delirium and dementia have overlapping features that complicate differential diagnosis. Delirium symptoms overshadow dementia symptoms when they co-occur, but delirium phenomenology in comorbid cases has not been compared to both conditions alone. METHODS: Consecutive adults with DSM-IV delirium, dementia, comorbid delirium-dementia and cognitively intact controls were assessed using the Revised Delirium Rating Scale (DRS-R98) and Cognitive Test for Delirium (CTD). RESULTS: Delirium and comorbid delirium-dementia groups had comparable DRS-R98 and CTD total scores, which were greater than in dementia or control groups. On the DRS-R98, multiple non-cognitive symptoms, inattention and disorientation were more severe in delirium groups compared with dementia-alone. Patients with dementia differed from both delirium groups on the CTD test of attention. Spatial span backwards was significantly lower in all patients with cognitive impairment (delirium, comorbid delirium-dementia, dementia alone) compared to controls, whereas spatial span forwards distinguished delirium groups from dementia. CONCLUSIONS: Delirium phenomenology is similar with or without comorbid dementia. A wide range of neuropsychiatric symptoms distinguish delirium from dementia. Spatial span forward is disproportionately diminished in delirium suggesting usefulness as a differentiating screening test.

Validating a new clinical subtyping scheme for delirium with electronic motion analysis.

The usefulness of motor subtypes of delirium is unclear due to inconsistency in sub-typing methods and a lack of validation with objective measures of activity. The activity of 40 patients was measured with 24 h accelerometry monitoring. Patients with Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) delirium (n=30) were allocated into hyperactive, hypoactive and mixed motor subtypes. Delirium subtypes differed in relation to overall amount of activity, including movement in both sagittal and transverse planes. Differences were greater in the daytime and during the early evening 'sundowning' period. Frequency of postural changes was the most discriminating measure examined. Clinical subtypes of delirium defined by observed motor behaviour on the ward differ in electronically measured activity levels.

Comparison of novel tools with traditional cognitive tests in detecting delirium in elderly medical patients.

BACKGROUND: Efficient detection of delirium and comorbid delirium-dementia is a key diagnostic challenge. Development of new, efficient delirium-focused methods of cognitive assessment is a key challenge for improved detection of neurocognitive disorders in everyday clinical practice. AIM: To compare the accuracy of two novel bedside tests of attention, vigilance and visuospatial function with conventional bedside cognitive tests in identifying delirium in older hospitalized patients. METHODS: 180 consecutive elderly medical inpatients (mean age 79.6 ± 7.2; 51% female) referred to a psychiatry for later life consultation-liaison service with delirium, dementia, comorbid delirium-dementia and cognitively intact controls. Participants were assessed cross-sectionally with conventional bedside cognitive tests [WORLD, Months Backward test (MBT), Spatial span, Vigilance A and B, Clock Drawing test and Interlocking Pentagons test] and two novel cognitive tests [Lighthouse test, Letter and Shape Drawing test (LSD)-4]. RESULTS: Neurocognitive diagnoses were delirium (n = 44), dementia (n = 30), comorbid delirium-dementia (n = 60) and no neurocognitive disorder (n = 46). All conventional tests had sensitivity of > 70% for delirium, with best overall accuracy for the Vigilance-B (78.3%), Vigilance-A (77.8%) and MBT (76.7%) tests. The sustained attention component of the Lighthouse test was the most distinguishing of delirium (sensitivity 84.6%; overall accuracy 75.6%). The LSD-4 had sensitivity of 74.0% and overall accuracy 74.4% for delirium identification. Combining tests allowed for enhanced sensitivity (> 90%) and overall accuracy (≥ 75%) with the highest overall accuracy for the combination of MBT-Vigilance A and the combined Vigilance A and B tests (both 78.3%). When analyses were repeated for those with dementia, there were similar findings with the MBT-Vigilance A the most accurate overall combination (80.0%). Combining the Lighthouse-SA with the LSD-4, a fail in either test had sensitivity for delirium of 91.4 with overall accuracy of 74.4%. CONCLUSION: Bedside tests of attention, vigilance and visuospatial ability can help to distinguish neurocognitive disorders, including delirium, from other presentations. The Lighthouse test and the LSD-4 are novel tests with high accuracy for detecting delirium.

Liver X receptor inhibition potentiates mitotane-induced adrenotoxicity in ACC.

Adrenocortical carcinoma (ACC) is a rare aggressive malignancy with a poor outcome largely due to limited treatment options. Here, we propose a novel therapeutic approach through modulating intracellular free cholesterol via the liver X receptor alpha (LXRα) in combination with current first-line pharmacotherapy, mitotane. H295R and MUC-1 ACC cell lines were pretreated with LXRα inhibitors in combination with mitotane. In H295R, mitotane (20, 40 and 50 µM) induced dose-dependent cell death; however, in MUC-1, this only occurred at a supratherapeutic concentration (200 µM). LXRα inhibition potentiated mitotane-induced cytotoxicity in both cell lines. This was confirmed through use of the CompuSyn model which showed moderate pharmacological synergism and was indicative of apoptotic cell death via an increase in annexinV and cleaved-caspase 3 expression. Inhibition of LXRα was confirmed through downregulation of cholesterol efflux pumps ABCA1 and ABCG1; however, combination treatment with mitotane attenuated this effect. Intracellular free-cholesterol levels were associated with increased cytotoxicity in H295R (r2 = 0.5210) and MUC-1 (r2 = 0.9299) cells. While both cell lines exhibited similar levels of free cholesterol at baseline, H295R were cholesterol ester rich, whereas MUC-1 were cholesterol ester poor. We highlight the importance of LXRα mediated cholesterol metabolism in the management of ACC, drawing attention to its role in the therapeutics of mitotane sensitive tumours. We also demonstrate significant differences in cholesterol storage between mitotane sensitive and resistant disease.