OBJECTIVE:Disrupted Brain dynamics are implicated in delirium. We aimed to better understand the characteristics of functional brain activity as a model for delirium. METHODS:Measurement of functional brain connectivity at rest and during task-based activities in acutely delirious patients in a convenience sample of patients with delirium versus controls. Dynamic jumps between discrete brain states were modelled using the hidden Markov modelling (HMM), an analytical framework that posits the existence of distinct states. Fractional occupancy (FO); the percentage (%) of time any state was active, lifetime; the average time in a given state and switchrate; number of switches per minute, were calculated during rest and task. RESULTS:Eleven patients were recruited, six had delirium. In the delirious group, 3 were female and the average age was 81 years. In the non-delirious group, 3 were female and the average age was 82 years. Fractional occupancy was no different between delirious and controls across the 10 canonical states (range p=0.09-0.89). Lifetime state dwell time was no different between delirium and controls (range of p=0.11-0.96). The switchrate between all states was no different between delirious cases and controls at rest (6.76 vs. 6.71; p=0.1) and during task (7.26 vs. 7.92; p=0.71). Delirium severity and switchrate correlation was r=-0.29; p=0.39. CONCLUSION:A functional MRI paradigm including incorporation of novel task state has shown proof of principle in delirium. Whilst there has been previously shown to be hierarchical dissolution during delirium, there was no difference in functional brain activity shown in this study. The study was approved by the Metro North Reviewing Ethics Committee [Ref No: HREC/17/QRBW/622].

This study aimed to identify characteristics associated with cognitive impairment in older individuals with obstructive sleep apnoea (OSA) using the Addenbrooke’s Cognitive Examination-Revised (ACE-R) that could aid in stratifying those at higher risk for impairment. We analysed existing cross-sectional datasets that measured the performance of 89 adult patients (aged 50–85 years) with OSA on the ACE-R cognitive test. Receiver operating characteristic curves and logistic regression analysis were utilised to identify associations between impairment status and various factors, including demographic characteristics, self-reported sleepiness, cognitive complaints, and OSA severity. According to established thresholds (ACE-R ≤ 88), 36

Consciousness, at its simplest, represents awareness of self in relation to the outside world. This can be divided further into the reasoning and rationality of Access consciousness (A-C) versus the experiential and ‘what it’s like’ of Phenomenal consciousness (P-C). A-C is directly measurable, using standard tests of cognition and memory. However, owing to the subjective nature of P-C, its direct testability remains problematic. We have previously derived indirect measures of P-C that incorporates a combination of subjective questions that are informed by objective dimensions of A-C. This battery of questions have shown sound proof of principle but have not yet been fully tested in the clinical space. As a bridge to clinical validation and in the challenge of a quantification gap, a thought experiment (TE) provides supporting evidence from the philosophy of science. We propose testing the foundational principles upon which operationalization of P-C questions has been designed through the prism of such a TE. We identified that a late-stage theory confirmation type of TE was appropriate for context. In the absence of suitable candidate TEs from cognitive science, we explored adaptation of a classical thought experiment from quantum physics. The ‘Schrödinger’s cat’ TE was refined for purpose into a novel ‘Schrödinger’s cat and mouse’ TE. Using this novel TE, our stated theories on consciousness, specifically P-C, and means of testing resonate with disorders of consciousness, not least delirium.

OBJECTIVE(S):The identification of cause(s) of delirium remains a clinical challenge within medicine. Our group have previously successfully developed and tested the Aetiology in Delirium-Decision Support Tool (AiD-DST). The AiD-DST is designed to help medical professionals close the gap on the detection of cause(s) of delirium. Here, we report on use of AiD-DST in the real-world setting. METHODS:A real-world implementation study of the AiD-DST within a general medical ward of a metropolitan hospital was conducted over a 10-week period. A mixed method evaluation was performed based upon the RE-AIM Framework that incorporates reach, effectiveness, adoption, implementation and maintenance of an intervention. RESULTS:Reach: fifty-three out of 87 (61%) eligible doctors consented to participation in the study. EFFECTIVENESS:A mean of 4.3 diagnoses were generated per patient with no difference in frequency when compared with historical control (z = 1.36; p = .17). Average usability score was 5.86 (SD = 1.15) on a 7-point scale, with 93% of respondents being satisfied with the AiD-DST. Free text feedback comprised themes of accessibility, ergonomics, diagnostic accuracy and applicability of AiD-DST to related conditions. IMPLEMENTATION:Instrument completion rate was 98% (n = 49/50), with a median completion time of 90 s. Maintenance: Sixty-seven % of uses of AiD-DST occurred in the second half of the study (p = .3). Following the initiation period there was an increase in use (r = .79; p = 02). CONCLUSION:Proof of principle was demonstrated for local implementation of a diagnostic support tool (AiD-DST).

Brain waste is cleared via a cerebrospinal fluid (CSF) pathway, the glymphatic system, whose dysfunction may underlie many brain conditions. Previous studies show coherent vascular oscillation, measured by blood oxygenation level-dependent (BOLD) fMRI, couples with CSF inflow to drive fluid flux. Yet, how this coupling is regulated, whether it mediates waste clearance, and why it is impaired remain unclear. Here we demonstrate that cholinergic neurons modulate BOLD-CSF coupling and glymphatic function. We find BOLD-CSF coupling correlates cortical cholinergic activity in aged humans. Lesioning basal forebrain cholinergic neurons in female mice impairs glymphatic efflux and associated changes in BOLD-CSF coupling, arterial pulsation and glymphatic influx. An acetylcholinesterase inhibitor alters these dynamics, primarily through peripheral mechanisms. Our results suggest cholinergic loss impairs glymphatic function by a neurovascular mechanism, potentially contributing to pathological waste accumulation. This may provide a basis for developing diagnostics and treatments for glymphatic dysfunction.

Delirium has conventionally been considered a disorder of consciousness, but this remains a relatively unexamined precept. First, a review of the role of consciousness disruption in delirium is revised from an historical and diagnostic perspective. Second, consciousness measurement in routine assessment of delirium is considered. Conscious levels, comprising alertness and arousal, are most commonly used but are not representative of the multidimensionality of consciousness. Third, a justification for the exploration of phenomenal consciousness is presented. Three candidate dimensions of phenomenal consciousness are identified as the pre-reflective state, phenomenal experience, and reflective thought. Finally, the clinical implications of a deeper understanding of delirium through measurement of phenomenal consciousness is considered.

Background Delirium has conventionally been considered a disorder of consciousness. Alertness and arousal are used as surrogates in clinical practice but are insufficient for the purposes of a more dimensional assessment of consciousness. We present a process of development and validation of candidate measures of phenomenal consciousness that could be applied to the diagnosis of delirium.Methods First, a narrative review of available instruments in the fields of phenomenal consciousness, including prereflective consciousness, the phenomenal-sensed experience and reflective thought, was undertaken. Eligibility of tools in the context of applicability to delirium was based upon objectivity in test interpretation and the requirement for tester administration. Second, where there was a gap in suitable cognitive tools, new items were derived using the silent generation technique. A process of face and construct validity using a diverse panel of experts was performed, and readability was evaluated.Results 814 articles were screened from the literature review. Fourteen candidate tools were reported from the three domains of phenomenal consciousness. One of these met the eligibility criteria for a delirium assessment. Fifty-seven new tests of phenomenal consciousness were identified. After a process of item reduction, a total of 26 individual tests were identified. After content validity, 22 of the 26 items were retained. The scale average content validity index was 0.89. The agreement between raters was between 80% and 97%. 100% of responses for face validity were rated as positive. Flesch Reading Ease Score was 91.6 (very easy to read).Conclusions Candidate measures of phenomenal consciousness are described, and early validity studies are promising.

Background: Electronic delirium -screening tools are an emergent area of research. Objective: The objective of this study was to summarise the development and performance characteristics of electronic screening tools in delirium. Methods: Searches were conducted in Pubmed, Embase, and CINAHL Complete databases to identify electronic delirium -screening tools. Results: Five electronic delirium -screening tools were identi fied and reviewed. Two were designed for and tested within a medical setting, and three were applied to intensive care. Adaptive design features, such as skip function to reduce test burden, were variably integrated into instrument design. All tools were shown to have acceptable psychometric properties, but validation studies were largely incomplete. Conclusions: Electronic delirium -screening tools are an exciting area of development and may offer hope for improved uptake of delirium screening. (c) 2023 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

OBJECTIVES:Following a user-centred redesign and refinement process of an electronic delirium screening tool (eDIS-MED), further accuracy assessment was performed prior to anticipated testing in the clinical setting. METHODS:Content validity of each of the existing questions was evaluated by an expert group in the domains of clarity, relevance and importance. Questions with a Content Validity Index (CVI) <0.80 were reviewed by the development group for potential revision. Items with CVI <0.70 were discarded. Next, face validity of the entirety of the tests was conducted and readability measured. RESULTS:A panel of five clinical experts evaluated the test battery comprising eDIS-MED. The content validity process endorsed 61 items. The overall scale CVI was 0.92. Eighty-eight per cent of the responses with regard to question relevancy, usefulness and appropriateness were positive. The questions were deemed fifth grade level and very easy to read. CONCLUSIONS:A revised electronic screening tool was shown to be accurate according to an expert group. A clinical validation study is planned.

Abstract Introduction Delirium is a common condition in older hospitalised patients causing high morbidity and mortality. The neurobiological basis for delirium is uncertain and, for numerous reasons, research in this area has been limited. Several recent studies have demonstrated that functional neuroimaging in delirium is achievable and has suggested that a brain region termed the default mode network (DMN), may play a cardinal role in delirium pathogenesis. We set out to develop a pilot study to demonstrate that it is feasible to undertake functional magnetic resonance imaging (fMRI) scans in older patients with acute delirium. Methods Observational pilot study obtaining a fMRI scan of inpatients in an Australian, tertiary hospital, geriatric ward. Eligible patients diagnosed as delirious by a geriatrician were compared against non-delirious controls. Informed consent was obtained. A novel scanning paradigm was developed. Sequences assed brain structure and functional networks in resting state and during a simple task of sustained attention and response inhibition. Results 11 participants have been scanned. 6 participants were delirious: mean age 81 years (range 77 – 85 years), 3 female. 5 participants were non-delirious: mean age 83.4years (range 79 -90 years), 2 female. 10 of the 11 participants completed the full imaging protocol, including task engagement. Head movement during scanning, was generally within acceptable limits. Data demonstrates considerable cortical atrophy and ventricular enlargement consistent with age. Preliminary fMRI analyses show a variable pattern of cortical recruitment during task engagement in delirious patients. Conclusions These findings show it is ethically and logistically feasible to engage elderly patients with acute delirium into a high end structural and functional imaging study.

Dysfunction of the cholinergic basal forebrain (BF) neurotransmitter system, including cholinergic axon denervation of the cortex, plays an important role in cognitive decline and dementia. The association of cortical cholinergic denervation with diverse cognitive profiles in dementia, particularly at early stages, has not yet been fully explored. We assessed the relationship of cholinergic denervation in the cortex measured using 18 F-fluoroethoxybenzovesamicol (FEOBV) with cognitive decline at an early stage of dementia. Participants (8 with mild cognitive impairment (MCI) and 10 cognitively unimpaired (CU) controls, aged 60-86, 55.6% female, MMSE = 28.7±1.5) underwent neuropsychological assessment and FEOBV PET imaging. The neuropsychological battery of tests included measures of memory, executive function, attention and language. Domain-specific composite scores were calculated by averaging z-scores of the related tests or subtasks within a domain. FEOBV images were co-registered to the concurrent structural MRI and normalised to the supratentorial white matter reference region resulting in a standardized uptake value ratio (SUVR). Voxel-wise analysis was performed on normalised FEOBV images to investigate associations with clinical diagnosis and domain-specific cognitive performance. Voxel-based morphometry was also performed to rule out differences in brain morphology. All analyses were corrected for age, sex and total intracranial volume and adjusted for multiple comparisons. The MCI group showed significantly lower global FEOBV SUVR in the cortex although only a focal cluster of reductions near the right middle temporal gyrus was found in the voxel-wise comparisons. When associations with cognitive performance profiles were assessed in the full cohort, regional positive correlations were found between FEOBV SUVR and cognitive scores across different domains (Figure 1), although these did not include memory. For executive functioning, widespread correlation patterns were observed across both cortical and subcortical regions. Moreover, overlapping profiles were identified for all three cognitive domains of executive function, attention and language, which covered the anterior cingulate gyrus, olfactory cortex, calcarine cortex, middle temporal gyrus and caudate nucleus. We have demonstrated that the topographic profile of FEOBV retention correlated with reduced cognitive performance in different domains, suggesting that reduced cortical cholinergic terminal integrity is an important pathological feature of cognitive decline.

Background Delirium is frequently missed in clinical practice. We used a user-centred redesign process to evaluate and adapt an existing electronic delirium screening tool (eDIS-ICU) for use in the medical setting. Methods In phase 1, we conducted a brainstorming session to establish context for delirium screening tools in medicine. In phase 2, a pluralistic walkthrough of eDIS-ICU was performed to identify prospective usability in the medical setting. We then extracted positive and negative qualities of eDIS-ICU. In phase 3, recommendations for change were made. Results Pluralistic walkthrough highlighted that eDIS-ICU related to the key groups of functionality, diagnosis, links with management and potential integration with clinical information. Recommended changes to make eDIS-ICU suitable for use in a medical setting included the need for skip function, prior instructions and streamlined testing. Conclusion A human-centred redesign created a pilot electronic delirium screening tool for use in a general medical setting (eDIS-MED).

Introduction Delirium is frequently multifactorial, and causes are often missed in clinical practice. The Aetiology in Delirium - Diagnostic Support Tool (AiD-DST) was developed to improve recognition of the causes. We undertook an evaluation of an electronic version of AiD-DST. Methods A development and evaluation life cycle of improvement was used. In phase 1, alpha testing among the development group evaluated technical performance of AiD-DST. In phase 2, we performed a cycle of beta testing among junior doctors to assess impressions of AiD-DST using Think Aloud methodology. We grouped responses into themes and made changes to AiD-DST by the development group accordingly. In phase 3, usability and acceptance of AiD-DST was assessed using the mHealth App Usability Questionnaire (MAUQ). Results In phase 1, software issues were identified, and modifications made. In phase 2, feedback was obtained from 29 junior doctors. Three cycles of feedback were obtained. The number of items identified after each cycle were 20, 12 and 7, respectively. Content was grouped into themes of; ‘style and grammar’, ‘formatting’, ‘IT’, ‘missed diagnosis’ and ‘other concerns.’ In phase 3, 20 participants completed MAUQ questionnaire. Overall, the average score was 6.36 (SD=0.8) with 7 as the highest attainable score. This translates to agreement up to strong agreement concerning usability of AiD-DST. Conclusion After a process of optimisation, AiD-DST has been shown to be a usable and potentially useful diagnostic support tool to help junior doctors identify cause(s) of delirium. An implementation study is planned.

Dysfunction of the cholinergic basal forebrain (BF) neurotransmitter system, including cholinergic axon denervation of the cortex, plays an important role in cognitive decline and dementia. A validated method to directly quantify cortical cholinergic terminal integrity enables exploration of the involvement of this system in diverse cognitive profiles associated with dementia, particularly at a prodromal stage. In this study, we used the radiotracer [18F]-fluoroethoxybenzovesamicol (FEOBV) as a direct measure of cholinergic terminal integrity and investigated its value for the assessment of cholinergic denervation in the cortex and associated cognitive deficits. Eighteen participants (8 with mild cognitive impairment (MCI) and 10 cognitively unimpaired controls) underwent neuropsychological assessment and brain imaging using FEOBV and [18F]-florbetaben for amyloid-β imaging. The MCI group showed a significant global reduction of FEOBV retention in the cortex and in the parietal and occipital cortices specifically compared to the control group. The global cortical FEOBV retention of all participants positively correlated with the BF, hippocampus and grey matter volumes, but no association was found between the global FEOBV retention and amyloid-β status. Topographic profiles from voxel-wise analysis of FEOBV images revealed significant positive correlations with the cognitive domains associated with the underlying cortical areas. Overlapping profiles of decreased FEOBV were identified in correlation with impairment in executive function, attention and language, which covered the anterior cingulate gyrus, olfactory cortex, calcarine cortex, middle temporal gyrus and caudate nucleus. However, the absence of cortical atrophy in these areas suggested that reduced cholinergic terminal integrity in the cortex is an important factor underlying the observed cognitive decline in early dementia. Our results provide support for the utility and validity of FEOBV PET for quantitative assessment of region-specific cholinergic terminal integrity that could potentially be used for early detection of cholinergic dysfunction in dementia following further validation in larger cohorts.

Introduction: Delirium, a common complication of an intensive care unit (ICU) admission, is inconsistently diagnosed by clinicians. Current screening tools require specialist expertise and/or training. Some are time-consuming to administer, and reliability in routine clinical practice is questionable. An innovative app designed to enable efficient and sensitive screening for delirium without specialist training (eDIS-ICU) has recently been described. This pilot study compared the eDIS-ICU against the reference standard expert assessment using DSM-V (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) criteria and the Confusion Assessment Method for the ICU (CAM-ICU). Methods: In this prospective, single-centre pilot study, a convenience sample of 29 ICU patients were recruited at a tertiary referral hospital between November 2018 and August 2019. After obtaining written consent, demographic and clinical data were collected, and the patients were screened for delirium using eDIS-ICU and CAM-ICU by two clinician researchers in random order. The patients were also assessed for presence of delirium independently by an expert clinician using a structured interview to diagnose as per DSM-V criteria. The results of screening and diagnosis were tabulated to allow comparison of screening tools against diagnosis; sensitivity and specificity of the tools were calculated. Results: Seven participants were diagnosed with delirium as per DSM-V criteria. The eDIS-ICU tool correctly identified six of these participants compared with two identified by CAM-ICU. The sensitivity of the eDIS-ICU tool was 86% (95% confidence interval [CI] = 81.5-10 0.0) compared with 29% (95% CI = 5.1 -69.7) for CAM-ICU (p < 0.05), and the specificity was 73% (95% CI = 81.5-100.0) versus 96% (95% CI = 75.1-99.8), respectively. Conclusion: The simple and novel eDIS-ICU delirium screening tool was noninferior to the CAM-ICU in detecting delirium as per DSM-V criteria. A definitive validation study is warranted. Crown Copyright (c) 2021 Published by Elsevier Ltd on behalf of Australian College of Critical Care Nurses Ltd. All rights reserved.

Abstract Background Persons with dementia commonly experience a range of behavioural and psychological symptoms, including agitation, aggression, perceptual disturbances, and depression. While psychotropic medications are regularly prescribed to mitigate these symptoms, these agents also carry a broad adverse effect profile. This study aimed to characterize psychotropic medication use in patients with dementia, as well as identify prescribing factors associated with falls in this cohort. Methods This retrospective study collected longitudinal demographic and medication data from all patients admitted to a neuro‐cognitive unit at an Australian metropolitan hospital over a 2‐year period. Psychotropic polypharmacy and psychotropic agent use per patient‐fortnight were investigated for their association with inpatient falls. Results All patients (n = 147) were prescribed at least one psychotropic medication, with 96% receiving anti‐psychotic medications and 90% receiving benzodiazepines. Patient fall rate was significantly associated with anticholinergic drug use (Incidence rate ratio: 2.2; P < .001), as well as concomitant use of ≥5 daily psychotropic agents (Incidence rate ratio: 3.1; P = .001). Conclusions Patients with dementia are routinely prescribed a wide variety of psychotropic medications. Use of anticholinergic drugs and psychotropic polypharmacy are correlated with fall incidence in persons with dementia.

Abstract Aims Obstructive sleep apnoea (OSA) occurs with greater frequency in advancing age. The resulting sleep fragmentation and oxygen desaturations may induce or contribute to neurodegeneration. As such, OSA may be an important modifiable risk factor for the development of dementia. However, the prevalence of OSA within the population with cognitive impairment remains uncharacterised. This study aims to assess the prevalence of OSA in patients attending a specialist memory clinic with either mild cognitive impairment (MCI) or mild stages of dementia (Mini-Mental State Examination (MMSE) > 20). Methods Eligible and consenting participants were asked to wear an ApneaLink™ (ResMed) device overnight that measured nasal airflow and oximetry to generate a Respiratory Disturbance Index (RDI). The Epworth Sleepiness Scale (ESS) was used to evaluate subjective symptoms. Results 64 participants completed the study. Mean(±SD) age=76.1±9.2 years, MMSE=25.6±2.8, RDI=15.5±12.0. The distribution of normal, mild, moderate and severe OSA was 16%, 44%, 26% and 14% respectively. 84% of participants had an abnormal RDI (>5), with 40% being moderate to severe (RDI >15) where CPAP may be the recommended treatment. Mean ESS was 7.08±4.45 and not correlated with OSA severity. Conclusion The prevalence of OSA in MCI or early stages of dementia is high and represents a potential target for therapeutic intervention. Further research studies are required to determine whether treatment of OSA alters dementia progression.

BACKGROUND:recognition of the multifactorial causes of delirium represents a clinical challenge.OBJECTIVES:to develop and show proof of principle of a diagnostic support tool (DST) for identification of causes of delirium.METHODS:stage 1-development of the aetiology in delirium-diagnostic support tool (AiD-DST); stage 2-validation of the AiD-DST against reference standard diagnosis, based on clinical assessment from two independent consultant geriatricians.RESULTS:a series of eight steps AiD-DST were formulated by an expert group to identify possible causes of delirium. Forty inpatients admitted to a general medical unit with a consultant physician/geriatrician diagnosis of delirium were recruited, consented and reviewed against the AiD-DST. Mean age was 85.1 (standard deviation 7.9) years and 26 (65%) of participants were female. Participants had multiple chronic co-morbidities [median Charlson Comorbidity Index 7; interquartile range (IQR 6-9)] and median number of medications was 8 (IQR 6-11.75). Median number of causes of delirium detected on AiD-DST was 3 (IQR 3-4) versus 5 (IQR 3-6) using the reference standard diagnosis, with sensitivity of 88.8% (95% confidence interval, 81.6-93.9%) and specificity of 71.8% (63-79.5%).CONCLUSIONS:the aetiology in delirium DST shows promise in the identification of cause(s) in delirium.