[Quality development in Consultation and Liaison Psychiatry and Psychosomatics].

INTRODUCTION: Quality or quality development and the corresponding regulations are becoming increasingly important in the Swiss healthcare system, in particular due to the link with aspects of permission for the provision of services and financing. In doing so, the focus is directed to varying degrees on structural, processual or outcome criteria. Specific quality aspects of the specialist area consultation-liaison psychiatry and psychosomatics (CLPP) are compiled and the indicators derived from them are grouped according to the quality criteria mentioned. There are numerous requirements, the implementation of which requires considerable efforts from the service providers, not least because of the shortage of specialists and limited financial resources. The requirements listed should be continuously evaluated and developed as well as sensibly anchored in regulation. Linking quality requirements with corresponding financial aspects within the framework of national tanning structures as well as national and cantonal permission regulations should be sought.

Low Subicular Volume as an Indicator of Dementia-Risk Susceptibility in Old Age.

Introduction: Hippocampal atrophy is an established Alzheimer's Disease (AD) biomarker. Volume loss in specific subregions as measurable with ultra-high field magnetic resonance imaging (MRI) may reflect earliest pathological alterations. Methods: Data from positron emission tomography (PET) for estimation of cortical amyloid ß (Aß) and high-resolution 7 Tesla T1 MRI for assessment of hippocampal subfield volumes were analyzed in 61 non-demented elderly individuals who were divided into risk-categories as defined by high levels of cortical Aß and low performance in standardized episodic memory tasks. Results: High cortical Aß and low episodic memory interactively predicted subicular volume [F(3,57) = 5.90, p = 0.018]. The combination of high cortical Aß and low episodic memory was associated with significantly lower subicular volumes, when compared to participants with high episodic memory (p = 0.004). Discussion: Our results suggest that low subicular volume is linked to established indicators of AD risk, such as increased cortical Aß and low episodic memory. Our data support subicular volume as a marker of dementia-risk susceptibility in old-aged non-demented persons.

[Delirium Management in Palliative Care]. / Delirmanagement in der Palliative Care.

Delirium Management in Palliative Care Abstract. Delirium is one of the most common neuropsychiatric complications in patients with advanced incurable disease. End-of-life delirium is common but is often overlooked, undiagnosed or incorrectly diagnosed/untreated. Delirium should also be treated in a palliative situation - as far as possible - because persistent delirious states increase the patient's fragility, limit physical functionality and shorten the lifespan. In addition, acute states of confusion trigger high levels of distress in affected patients and their relatives, impair the quality of life and a dignified dying process. While hallucinations and visions at the end of life are interpreted as delirium in medicine and treated as such, this phenomenon is interpreted by philosophical and theological hermeneutics as a resource that can help patients and their relatives to reconcile with past life events and to deal with the process of dying. However, the occurrence of end-of-life visions as opposed to delirium has not yet been studied very much and requires more detailed exploration.

EEG-fMRI Signal Coupling Is Modulated in Subjects With Mild Cognitive Impairment and Amyloid Deposition.

Cognitive impairment indicates disturbed brain physiology which can be due to various mechanisms including Alzheimer's pathology. Combined functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) recordings (EEG-fMRI) can assess the interplay between complementary measures of brain activity and EEG changes to be localized to specific brain regions. We used a two-step approach, where we first examined changes related to a syndrome of mild cognitive impairment irrespective of pathology and then studied the specific impact of amyloid pathology. After detailed clinical and neuropsychological characterization as well as a positron emission tomography (PET) scans with the tracer 11-[C]-Pittsburgh Compound B to estimate cerebral amyloid deposition, 14 subjects with mild cognitive impairment (MCI) (mean age 75.6 SD: 8.9) according to standard criteria and 21 cognitively healthy controls (HCS) (mean age 71.8 SD: 4.2) were assessed with EEG-fMRI. Thalamo-cortical alpha-fMRI signal coupling was only observed in HCS. Additional EEG-fMRI signal coupling differences between HCS and MCI were observed in parts of the default mode network, salience network, fronto-parietal network, and thalamus. Individuals with significant cerebral amyloid deposition (amyloid-positive MCI and HCS combined compared to amyloid-negative HCS) displayed abnormal EEG-fMRI signal coupling in visual, fronto-parietal regions but also in the parahippocampus, brain stem, and cerebellum. This finding was paralleled by stronger absolute fMRI signal in the parahippocampus and weaker absolute fMRI signal in the inferior frontal gyrus in amyloid-positive subjects. We conclude that the thalamocortical coupling in the alpha band in HCS more closely reflects previous findings observed in younger adults, while in MCI there is a clearly aberrant coupling in several networks dominated by an anticorrelation in the posterior cingulate cortex. While these findings may broadly indicate physiological changes in MCI, amyloid pathology was specifically associated with abnormal fMRI signal responses and disrupted coupling between brain oscillations and fMRI signal responses, which especially involve core regions of memory: the hippocampus, para-hippocampus, and lateral prefrontal cortex.

Physical activity is associated with lower cerebral beta-amyloid and cognitive function benefits from lifetime experience-a study in exceptional aging.

BACKGROUND: Exceptional agers (85+ years) are characterized by preserved cognition presumably due to high cognitive reserve. In the current study, we examined whether personality, risk and protective factors for dementia as well as quality of life are associated with core features of Alzheimer's disease (amyloid-deposition and hippocampal volume) as well as cognition in exceptional aging. METHODS: We studied 49 exceptional agers (average 87.8 years, range 84-94 years), with preserved activities of daily living and absence of dementia. All participants received a detailed clinical and neuropsychological examination. We used established questionnaires to measure lifetime experience, personality, recent physical and cognitive activity as well as quality of life. Cerebral amyloid-deposition was estimated by 18-[F]-Flutemetamol-PET and manual hippocampal volumetry was performed on 3D T1 MRI images. RESULTS: In this sample of exceptional agers with preserved activities of daily living, we found intact cognitive performance in the subjects with the highest amyloid-load in the brain, but a lower quality of life with respect to autonomy as well as higher neuroticism. Higher self-reported physical activity in the last twelve months went with a lower amyloid load. Higher self-reported leisure-time/ not work-related activity went with better executive functioning at older age. CONCLUSION: Even in exceptional aging, high amyloid load may subtly influence personality and quality of life. Our findings support a close relationship between high physical activity and low amyloid-deposition and underscore the importance of extracurricular activities for executive functions. As executive functions are known to be a central resource for everyday functioning in fostering extracurricular activities may be effective in delaying the onset of dementia.

Reduced uptake of [11C]-ABP688, a PET tracer for metabolic glutamate receptor 5 in hippocampus and amygdala in Alzheimer's dementia.

INTRODUCTION: Metabotropic glutamate receptors play a critical role in the pathogenesis of Alzheimer's disease due to their involvement in processes of memory formation, neuroplasticity, and synaptotoxity. The objective of the current study was to study mGluR5 availability measured by [11 C]-ABP688 (ABP) in patients with clinically diagnosed Alzheimer's dementia (AD). METHODS: A bolus-infusion protocol of [11 C]-ABP688 was applied in 9 subjects with AD and 10 cognitively healthy controls (Controls) to derive distribution volume estimates of mGluR5. Furthermore, we also estimated cerebral perfusion by averaging early frame signal of initial ABP bolus injection. RESULTS: Subjects with Alzheimer's dementia (mean age: 77.3/SD 5.7) were older than controls (mean age: 68.5/SD: 9.6) and scored lower on the MMSE (22.1/SD2.7 vs. 29.0/SD0.8). There were no overall differences in ABP signal. However, distribution volume ratio (DVR) for ABP was reduced in the bilateral hippocampus (AD: 1.34/SD: 0.40 vs. Control: 1.84/SD:0.31, p = .007) and the bilateral amygdala (AD:1.86/SD:0.26 vs. Control:2.33/SD:0.37 p = .006) in AD patients compared to controls. Estimate of cerebral blood flow was reduced in the bilateral hippocampus in AD (AD:0.75/SD:0.10 vs. Control:0.86/SD:0.09 p = .02). CONCLUSION: Our findings demonstrate reduced mGluR5 binding in the hippocampus and amygdala in Alzheimer's dementia. Whether this is due to synaptic loss and/or consecutive reduction of potential binding sites or reflects disease inherent mechanisms remains to be elucidated in future studies.

Functional Brain Network Connectivity Patterns Associated With Normal Cognition at Old-Age, Local ß-amyloid, Tau, and APOE4.

Background: Integrity of functional brain networks is closely associated with maintained cognitive performance at old age. Consistently, both carrier status of Apolipoprotein E ε4 allele (APOE4), and age-related aggregation of Alzheimer's disease (AD) pathology result in altered brain network connectivity. The posterior cingulate and precuneus (PCP) is a node of particular interest due to its role in crucial memory processes. Moreover, the PCP is subject to the early aggregation of AD pathology. The current study aimed at characterizing brain network properties associated with unimpaired cognition in old aged adults. To determine the effects of age-related brain change and genetic risk for AD, pathological proteins ß-amyloid and tau were measured by Positron-emission tomography (PET), PCP connectivity as a proxy of cognitive network integrity, and genetic risk by APOE4 carrier status. Methods: Fifty-seven cognitively unimpaired old-aged adults (MMSE = 29.20 ± 1.11; 73 ± 8.32 years) were administered 11C Pittsburgh Compound B and 18F Flutemetamol PET for assessing ß-amyloid, and 18F AV-1451 PET for tau. Individual functional connectivity seed maps of the PCP were obtained by resting-state multiband BOLD functional MRI at 3-Tesla for increased temporal resolution. Voxelwise correlations between functional connectivity, ß-amyloid- and tau-PET were explored by Biological Parametric Mapping (BPM). Results: Local ß-amyloid was associated with increased connectivity in frontal and parietal regions of the brain. Tau was linked to increased connectivity in more spatially distributed clusters in frontal, parietal, occipital, temporal, and cerebellar regions. A positive interaction was observable for APOE4 carrier status and functional connectivity with brain regions characterized by increased local ß-amyloid and tau tracer retention. Conclusions: Our data suggest an association between spatially differing connectivity systems and local ß-amyloid, and tau aggregates in cognitively normal, old-aged adults, which is moderated by APOE4. Additional longitudinal studies may determine protective connectivity patterns associated with healthy aging trajectories of AD-pathology aggregation.

APOE4 moderates effects of cortical iron on synchronized default mode network activity in cognitively healthy old-aged adults.

INTRODUCTION: Apolipoprotein E ε4 (APOE4)-related genetic risk for sporadic Alzheimer's disease is associated with an early impairment of cognitive brain networks. The current study determines relationships between APOE4 carrier status, cortical iron, and cortical network-functionality. METHODS: Sixty-nine cognitively healthy old-aged individuals (mean age [SD] 66.1 [± 7.2] years; Mini-Mental State Exam [MMSE] 29.3 ± 1.1) were genotyped for APOE4 carrier-status and received 3 Tesla magnetic resonance imaging (MRI) for blood oxygen level-dependent functional magnetic resonance imaging (MRI) at rest, three-dimensional (3D)-gradient echo (six echoes) for cortical gray-matter, non-heme iron by quantitative susceptibility mapping, and 18F-flutemetamol positron emission tomography for amyloid-ß. RESULTS: A spatial pattern consistent with the default mode network (DMN) could be identified by independent component analysis. DMN activity was enhanced in APOE4 carriers and related to cortical iron burden. APOE4 and cortical iron synergistically interacted with DMN activity. Secondary analysis revealed a positive, APOE4 associated, relationship between cortical iron and DMN connectivity. DISCUSSION: Our findings suggest that APOE4 moderates effects of iron on brain functionality prior to manifestation of cognitive impairment.

Delirium in the intensive care setting dependent on the Richmond Agitation and Sedation Scale (RASS): Inattention and visuo-spatial impairment as potential screening domains.

OBJECTIVE: In the intensive care setting, delirium is a common occurrence; however, the impact of the level of alertness has never been evaluated. Therefore, this study aimed to assess the delirium characteristics in the drowsy, as well as the alert and calm patient. METHOD: In this prospective cohort study, 225 intensive care patients with Richmond Agitation and Sedation Scale (RASS) scores of -1 - drowsy and 0 - alert and calm were evaluated with the Delirium Rating Scale-Revised-1998 (DRS-R-98) and the Diagnostic and Statistical Manual 4th edition text revision (DSM-IV-TR)-determined diagnosis of delirium. RESULTS: In total, 85 drowsy and 140 alert and calm patients were included. Crucial items for the correct identification of delirium were sleep-wake cycle disturbances, language abnormalities, thought process alterations, psychomotor retardation, disorientation, inattention, short- and long-term memory, as well as visuo-spatial impairment, and the temporal onset. Conversely, perceptual disturbances, delusions, affective lability, psychomotor agitation, or fluctuations were items, which identified delirium less correctly. Further, the severities of inattentiveness and visuo-spatial impairment were indicative of delirium in both alert- or calmness and drowsiness. SIGNIFICANCE OF RESULTS: The impairment in the cognitive domain, psychomotor retardation, and sleep-wake cycle disturbances correctly identified delirium irrespective of the level alertness. Further, inattentiveness and - to a lesser degree - visuo-spatial impairment could represent a specific marker for delirium in the intensive care setting meriting further evaluation.

Screening for delirium with the Intensive Care Delirium Screening Checklist (ICDSC): Symptom profile and utility of individual items in the identification of delirium dependent on the level of sedation.

OBJECTIVE: The importance of the proper identification of delirium, with its high incidence and adversities in the intensive care setting, has been widely recognized. One common screening instrument is the Intensive Care Delirium Screening Checklist (ICDSC); however, the symptom profile and key features of delirium dependent on the level of sedation have not yet been evaluated. METHOD: In this prospective cohort study, the ICDSC was evaluated versus the Diagnostic and Statistical Manual, 4th edition, text revision, diagnosis of delirium set as standard with respect to the symptom profile, and correct identification of delirium. The aim of this study was to identify key features of delirium in the intensive care setting dependent on the Richmond Agitation and Sedation Scale levels of sedation: drowsiness versus alert and calmness.ResultThe 88 delirious patients of 225 were older, had more severe disease, and prolonged hospitalization. Irrespective of the level of sedation, delirium was correctly classified by items related to inattention, disorientation, psychomotor alterations, inappropriate speech or mood, and symptom fluctuation. In the drowsy patients, inattention reached substantial sensitivity and specificity, whereas psychomotor alterations and sleep-wake cycle disturbances were sensitive lacked specificity. The positive prediction was substantial across items, whereas the negative prediction was only moderate. In the alert and calm patient, the sensitivities were substantial for psychomotor alterations, sleep-wake cycle disturbances, and symptom fluctuations; however, these fluctuations were not specific. The positive prediction was moderate and the negative prediction substantial. Between the nondelirious drowsy and alert, the symptom profile was similar; however, drowsiness was associated with alterations in consciousness.Significance of resultsIn the clinical routine, irrespective of the level of sedation, delirium was characterized by the ICDSC items for inattention, disorientation, psychomotor alterations, inappropriate speech or mood and symptom fluctuation. Further, drowsiness caused altered levels of consciousness.

Validation and Psychometric Properties of the German Version of the Delirium Motor Subtype Scale (DMSS).

Objective: Delirium has been characterized into its subtypes-hypoactive, hyperactive, mixed, or no motor subtype-along with the use of the Delirium Motor Symptom Scale (DMSS). The German version of this scale (DMSS-G), however, has not yet been validated. Method: We determined internal consistency, reliability, and validity of the DMSS-G in the surgical intensive care unit, using DSM-IV-TR criteria and the Delirium Rating Scale-Revised-98. Results: In total, 289 patients were included, and out of these, 122 were delirious. The DMSS-G showed excellent internal consistency (Cronbach's α = 0.92) and interrater reliability (Fleiss κ = 0.83). Additionally, the overall concurrent validity was substantial (Cramer's V = 0.69); within subtypes, hyperactive, hypoactive, or mixed, the concurrent validity remained at least substantial (Cohen's κ = 0.73-0.82) and the sensitivity ranged from 60% to 97%. In contrast, in those with no motor subtype, we found the concurrent validity (Cohen's κ = 0.31) and sensitivity to be low (22%). Overall, specificity for all individual subtypes was high (82% to 100%). The DMSS was very sensitive in both rating hyperactive and hypoactive motor symptoms of delirium. Conclusion: The DMSS-G is a highly reliable and valid instrument for detecting motor symptoms in delirium, which provides an accurate instrument to classify the motor subtypes of delirium.

Screening for delirium with the Intensive Care Delirium Screening Checklist (ICDSC): a re-evaluation of the threshold for delirium.

BACKGROUND: With its high incidence and subsequent adverse consequences in the intensive care setting, several instruments have been developed to screen for and detect delirium. One of the more commonly used is the Intensive Care Delirium Screening Checklist (ICDSC); however, the optimal cut-off score indicating delirium has been debated. METHODS: In this prospective cohort study, the ICDSC threshold for delirium set at ≥3, ≥4, or ≥5 was compared with the DSM-IV-TR-determined diagnosis of delirium (used as standard), and with the Confusion Assessment Method for the ICU (CAM-ICU), with respect to their concurrent validity. RESULTS: In total, 289 patients were assessed, including 122 with delirium. The cut-off score of ≥4 had several shortcomings: although 90% of patients with delirium were correctly classified, 23% remained undetected. The agreement with the DSM-IV-TR diagnosis of delirium was only moderate (Cohen's κ 0.59) and the sensitivity was only 62%. In contrast, when the cut-off was ≥3, 83% of patients with delirium were correctly classified and only 14.5% remained undetected. The agreement with DSM-IV-TR was substantial (Cohen's κ 0.68) and the sensitivity increased to 83%. The benefit of setting the cut-off at ≥5 was not convincing: although 90% of patients with delirium were correctly classified, 30% remained undetected. The concurrent validity was only moderate (Cohen's κ 0.44), and the sensitivity reached only 44%. Changing the ICDSC cut-off score did not strengthen the moderate agreement with the CAM-ICU (Cohen's κ 0.45-0.56). CONCLUSION: In clinical routine, decreasing the ICDSC threshold for delirium to ≥3 increased the accuracy in detecting delirium at the cost of over-identification and is therefore recommended as the optimal threshold. Increasing the cut-off score to ≥5 decreased the concurrent validity and sensitivity; in addition, the under-detection of delirium was substantial.

Low cortical iron and high entorhinal cortex volume promote cognitive functioning in the oldest-old.

The aging brain is characterized by an increased presence of neurodegenerative and vascular pathologies. However, there is substantial variation regarding the relationship between an individual's pathological burden and resulting cognitive impairment. To identify correlates of preserved cognitive functioning at highest age, the relationship between ß-amyloid plaque load, presence of small vessel cerebrovascular disease (SVCD), iron-burden, and brain atrophy was investigated. Eighty cognitively unimpaired participants (44 oldest-old, aged 85-96 years; 36 younger-old, aged 55-80 years) were scanned by integrated positron emission tomography-magnetic resonance imaging for assessing beta regional amyloid plaque load (18F-flutemetamol), white matter hyperintensities as an indicator of SVCD (fluid-attenuated inversion recovery-magnetic resonance imaging), and iron load (quantitative susceptibility mapping). For the oldest-old group, lower cortical volume, increased ß-amyloid plaque load, prevalence of SVCD, and lower cognitive performance in the normal range were found. However, compared to normal-old, cortical iron burden was lower in the oldest-old. Moreover, only in the oldest-old, entorhinal cortex volume positively correlated with ß-amyloid plaque load. Our data thus indicate that the co-occurrence of aging-associated neuropathologies with reduced quantitative susceptibility mapping measures of cortical iron load constitutes a lower vulnerability to cognitive loss.

Subsyndromal delirium in the intensive care setting: Phenomenological characteristics and discrimination of subsyndromal delirium versus no and full-syndromal delirium.

OBJECTIVE: Similar to delirium, its subsyndromal form has been recognized as the cause of diverse adverse outcomes. Nonetheless, the nature of this subsyndromal delirium remains vastly understudied. Therefore, in the following, we evaluate the phenomenological characteristics of this syndrome versus no and full-syndromal delirium. METHOD: In this prospective cohort study, we evaluated the Delirium Rating Scale-Revised, 1998 (DRS-R-98) versus the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) diagnostic criteria and examined the diagnosis of delirium with respect to phenomenological distinctions in the intensive care setting. RESULTS: Out of 289 patients, 36 with subsyndromal delirium versus 86 with full-syndromal and 167 without delirium were identified. Agreement with respect to the DSM-IV-TR diagnosis of delirium was perfect. The most common subtype in those with subsyndromal delirium was hypoactive, in contrast to mixed subtype in those with full-syndromal delirium versus no motor alterations in those without delirium. By presence and severity of delirium symptoms, subsyndromal delirium was intermediate. The ability of the DRS-R-98 items to discriminate between either form of delirium was substantial. Between subsyndromal and no delirium, the cognitive domain and sleep-wake cycle were more impaired and allowed a distinction with no delirium. Further, between full- and subsyndromal delirium, the prevalence and severity of individual DRS-R-98 items were greater. Although the differences between these two forms of delirium was substantial, the items were not very specific, indicating that the phenomenology of subsyndromal delirium is closer to full-syndromal delirium. SIGNIFICANCE OF RESULTS: Phenomenologically, subsyndromal delirium was found to be distinct from and intermediate between no delirium and full-syndromal delirium. Moreover, the greater proximity to full-syndromal delirium indicated that subsyndromal delirium represents an identifiable subform of full-syndromal delirium.

Delirium in the intensive care setting and the Richmond Agitation and Sedation Scale (RASS): Drowsiness increases the risk and is subthreshold for delirium.

INTRODUCTION: Sedation is a core concept in the intensive care setting, however, the impact of sedation on delirium has not yet been studied to date. METHODS: In this prospective cohort study, 225 patients with Richmond Agitation and Sedation (RASS) scores of -1 - drowsiness and 0 - alert- and calmness were assessed with the Delirium Rating Scale-Revised 1998 (DRS-R-98) and DSM-IV-TR-determined diagnosis of delirium assessing drowsiness versus alertness. RESULTS: By itself, drowsiness increased the odds for developing delirium eightfold (OR 7.88 p<0.001) and rates of delirium were 68.2 and 21.4%, respectively. Further, in the drowsy patient, delirium was more severe. In the presence of drowsiness, delirium was characterized by sleep-wake cycle disturbances and language abnormalities. These two features, in addition to psychomotor retardation, allowed the correct classification of delirium at RASS-1. The same features, in addition to thought abnormalities and the impairment in the cognitive domain, orientation, attention, short- and long-term memory representing the core domains of delirium, or the temporal onset were very sensitive towards delirium, however lacked specificity. Conversely, delusions, perceptual abnormalities and lability of affect representing the non-core domain were very specific for delirium in the drowsy, however, not very sensitive. In the absence of delirium, drowsiness caused attentional impairment and language abnormalities. CONCLUSION: Drowsiness increased the odds for developing delirium eightfold and caused more severe delirium, which was characterized by sleep-wake cycle and language abnormalities. Further, drowsiness by itself caused attentional impairment and language abnormalities, thus, with its disturbance in consciousness was subthreshold for delirium.

Memory performance-related dynamic brain connectivity indicates pathological burden and genetic risk for Alzheimer's disease.

BACKGROUND: The incidence of Alzheimer's disease (AD) strongly relates to advanced age and progressive deposition of cerebral amyloid-beta (Aß), hyperphosphorylated tau, and iron. The purpose of this study was to investigate the relationship between cerebral dynamic functional connectivity and variability of long-term cognitive performance in healthy, elderly subjects, allowing for local pathology and genetic risk. METHODS: Thirty seven participants (mean (SD) age 74 (6.0) years, Mini-Mental State Examination 29.0 (1.2)) were dichotomized based on repeated neuropsychological test performance within 2 years. Cerebral Aß was measured by 11C Pittsburgh Compound-B positron emission tomography, and iron by quantitative susceptibility mapping magnetic resonance imaging (MRI) at an ultra-high field strength of 7 Tesla (7T). Dynamic functional connectivity patterns were investigated by resting-state functional MRI at 7T and tested for interactive effects with genetic AD risk (apolipoprotein E (ApoE)-ε4 carrier status). RESULTS: A relationship between low episodic memory and a lower expression of anterior-posterior connectivity was seen (F(9,27) = 3.23, p < 0.008), moderated by ApoE-ε4 (F(9,27) = 2.22, p < 0.005). Inherent node-strength was related to local iron (F(5,30) = 13.2; p < 0.022). CONCLUSION: Our data indicate that altered dynamic anterior-posterior brain connectivity is a characteristic of low memory performance in the subclinical range and genetic risk for AD in the elderly. As the observed altered brain network properties are associated with increased local iron, our findings may reflect secondary neuronal changes due to pathologic processes including oxidative stress.

Delirium in the intensive care setting: A reevaluation of the validity of the CAM-ICU and ICDSC versus the DSM-IV-TR in determining a diagnosis of delirium as part of the daily clinical routine.

BACKGROUND: In the intensive care setting, delirium is a common occurrence that comes with subsequent adversities. Therefore, several instruments have been developed to screen for and detect delirium. Their validity and psychometric properties, however, remain controversial. METHOD: In this prospective cohort study, the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) and the Intensive Care Delirium Screening Checklist (ICDSC) were evaluated versus the DSM-IV-TR in the diagnosis of delirium with respect to their validity and psychometric properties. RESULTS: Out of some 289 patients, 210 with matching CAM-ICU, ICDSC, and DSM-IV-TR diagnoses were included. Between the scales, the prevalence of delirium ranged from 23.3% with the CAM-ICU, to 30.5% with the ICDSC, to 43.8% with the DSM-IV-TR criteria. The CAM-ICU showed only moderate concurrent validity (Cohen's κ = 0.44) and sensitivity (50%), but high specificity (95%). The ICDSC also reached moderate agreement (Cohen's κ = 0.60) and sensitivity (63%) while being very specific (95%). Between the CAM-ICU and the ICDSC, the concurrent validity was again only moderate (Cohen's κ = 0.56); however, the ICDSC yielded higher sensitivity and specificity (78 and 83%, respectively). SIGNIFICANCE OF RESULTS: In the daily clinical routine, neither the CAM-ICU nor the ICDSC, common tools used in screening and detecting delirium in the intensive care setting, reached sufficient concurrent validity; nor did they outperform the DSM-IV-TR diagnostic criteria with respect to sensitivity or positive prediction, but they were very specific. Thus, the non-prediction by the CAM-ICU or ICDSC did not refute the presence of delirium. Between the CAM-ICU and ICDSC, the ICDSC proved to be the more accurate instrument.

Brief assessment of delirium subtypes: Psychometric evaluation of the Delirium Motor Subtype Scale (DMSS)-4 in the intensive care setting.

OBJECTIVE: The management of and prognosis for delirium are affected by its subtype: hypoactive, hyperactive, mixed, and none. The DMSS-4, an abbreviated version of the Delirium Motor Symptom Scale, is a brief instrument for the assessment of delirium subtypes. However, it has not yet been evaluated in an intensive care setting. METHOD: We performed a prospective/descriptive cohort study in order to determine the internal consistency, reliability, and validity of the relevant items of the DMSS-4 versus the Delirium Rating Scale-Revised-98 (DRS-R-98) and the original DMSS in a surgical intensive care setting. RESULTS: A total of 289 elderly, predominantly male patients were screened for delirium, and 122 were included in our sample. The internal consistency of the DMSS-4 items was excellent (Cronbach's α = 0.92), and between the DMSS-4 and DRS-R-98 the overall concurrent validity was substantial (Cramer's V = 0.67). Within individual motor subtypes, concurrent validity remained at least substantial (Cohen's κ = 0.65-0.81) and sensitivity high (69.8 to 82.2%), in contrast to those of the no-motor subtype, with less validity and sensitivity (κ = 0.28, 22%). Similarly, total concurrent validity between the DMSS-4 and the original DMSS reached perfection (Cramer's V = 0.83), as did agreement between the subtypes (κ = 0.83-0.92), while sensitivity remained high (88.2-100%). Only in those with delirium with no-motor subtype was agreement moderate (κ = 0.56) and sensitivity lower (67%). Specificity was high across all subtypes (91.2-99.1%). The DMSS-4 yielded very sensitive ratings, particularly for hypoactive and hyperactive motor symptoms, and interrater agreement was excellent (Fleiss's κ = 0.83). SIGNIFICANCE OF RESULTS: We found the DMSS-4 to be a most reliable and valid brief assessment of delirium in characterizing the subtypes of delirium in an intensive care setting, with increased sensitivity to hypoactive and hyperactive motor alterations.

Arterial spin labeling imaging reveals widespread and Aß-independent reductions in cerebral blood flow in elderly apolipoprotein epsilon-4 carriers.

Changes in cerebral blood flow are an essential feature of Alzheimer's disease and have been linked to apolipoprotein E-genotype and cerebral amyloid-deposition. These factors could be interdependent or influence cerebral blood flow via different mechanisms. We examined apolipoprotein E-genotype, amyloid beta-deposition, and cerebral blood flow in amnestic mild cognitive impairment using pseudo-continuous arterial spin labeling MRI in 27 cognitively normal elderly and 16 amnestic mild cognitive impairment participants. Subjects underwent Pittsburgh Compound B (PiB) positron emission tomography and apolipoprotein E-genotyping. Global cerebral blood flow was lower in apolipoprotein E ɛ4-allele carriers (apolipoprotein E4+) than in apolipoprotein E4- across all subjects (including cognitively normal participants) and within the group of cognitively normal elderly. Global cerebral blood flow was lower in subjects with mild cognitive impairment compared with cognitively normal. Subjects with elevated cerebral amyloid-deposition (PiB+) showed a trend for lower global cerebral blood flow. Apolipoprotein E-status exerted the strongest effect on global cerebral blood flow. Regional analysis indicated that local cerebral blood flow reductions were more widespread for the contrasts apolipoprotein E4+ versus apolipoprotein E4- compared with the contrasts PiB+ versus PiB- or mild cognitive impairment versus cognitively normal. These findings suggest that apolipoprotein E-genotype exerts its impact on cerebral blood flow at least partly independently from amyloid beta-deposition, suggesting that apolipoprotein E also contributes to cerebral blood flow changes outside the context of Alzheimer's disease.

Management of Gamma-Butyrolactone Dependence with Assisted Self-Administration of GBL.

Gamma-hydroxybutyric acid (GHB) and its liquid precursor gamma-butyrolactone (GBL) have become increasingly popular beyond the clubbing culture resulting in daily consumption and dependence in the broader population. This case report illustrates the challenges of managing GHB-withdrawal and a possibly superior future approach of its management by titration and tapering of the addictive agent.