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Author(s): Thomas A. Jackson 1,2,*, John R. F. Gladman 3, Rowan H. Harwood 4, Alasdair M. J. MacLullich 5, Elizabeth L. Sampson 6, Bart Sheehan 7, Daniel H. J. Davis [...]

Background Delirium is common, distressing and associated with poor outcomes. Previous studies investigating the impact of delirium on cognitive outcomes have been limited by incomplete ascertainment of baseline cognition or lack of prospective delirium assessments. This study quantified the association between delirium and cognitive function over time by prospectively ascertaining delirium in a cohort aged ≥ 65 years in whom baseline cognition had previously been established. Methods For 12 months, we assessed participants from the Cognitive Function and Ageing Study II-Newcastle for delirium daily during hospital admissions. At 1-year, we assessed cognitive decline and dementia in those with and without delirium. We evaluated the effect of delirium (including its duration and number of episodes) on cognitive function over time, independently of baseline cognition and illness severity. Results Eighty two of 205 participants recruited developed delirium in hospital (40%). One-year outcome data were available for 173 participants: 18 had a new dementia diagnosis, 38 had died. Delirium was associated with cognitive decline (−1.8 Mini-Mental State Examination points [95% CI –3.5 to –0.2]) and an increased risk of new dementia diagnosis at follow up (OR 8.8 [95% CI 1.9–41.4]). More than one episode and more days with delirium (>5 days) were associated with worse cognitive outcomes. Conclusions Delirium increases risk of future cognitive decline and dementia, independent of illness severity and baseline cognition, with more episodes associated with worse cognitive outcomes. Given that delirium has been shown to be preventable in some cases, we propose that delirium is a potentially modifiable risk factor for dementia. [ABSTRACT FROM AUTHOR]

Background: Delirium is common, affecting at least 20% of older hospital inpatients. It is widely accepted that delirium is associated with dementia but the degree of causation within this relationship is unclear. Previous studies have been limited by incomplete ascertainment of baseline cognition or a lack of prospective delirium assessments. There is an urgent need for an improved understanding of the relationship between delirium and dementia given that delirium prevention may plausibly impact upon dementia prevention. A well-designed, observational study could also answer fundamental questions of major importance to patients and their families regarding outcomes after delirium. The Delirium and Cognitive Impact in Dementia (DECIDE) study aims to explore the association between delirium and cognitive function over time in older participants. In an existing population based cohort aged 65 years and older, the effect on cognition of an episode of delirium will be measured, independent of baseline cognition and illness severity. The predictive value of clinical parameters including delirium severity, baseline cognition and delirium subtype on cognitive outcomes following an episode of delirium will also be explored.Methods: Over a 12 month period, surviving participants from the Cognitive Function and Ageing Study II-Newcastle will be screened for delirium on admission to hospital. At the point of presentation, baseline characteristics along with a number of disease relevant clinical parameters will be recorded. The progression/resolution of delirium will be monitored. In those with and without delirium, cognitive decline and dementia will be assessed at one year follow-up. We will evaluate the effect of delirium on cognitive function over time along with the predictive value of clinical parameters.Discussion: This study will be the first to prospectively elucidate the size of the effect of delirium upon cognitive decline and incident dementia. The results will be used to inform future dementia prevention trials that focus on delirium intervention. [ABSTRACT FROM AUTHOR]

Background: delirium is under-recognised in comparison to other common and serious acute disorders. A 2006 survey of UK junior doctors (not undertaking specialist training) identified poor knowledge of the diagnostic criteria and treatment of delirium. We hypothesised that increased prominence accorded to delirium in the form of national initiatives and guidelines may have had an impact on understanding among junior doctors. Objective: we repeated a multi-centre survey of knowledge of and attitudes to delirium in junior doctors (not undertaking specialist training) assessing unselected acute medical presentations (the 'medical take'). Design: questionnaire-based survey in 48 acute hospitals in UK and Ireland. Methods: we used questionnaires designed to test understanding of delirium, including prevalence, knowledge of the DSM-IV diagnostic criteria, use of specific screening tools, association with adverse outcomes and pharmacological management. Results: one thousand two hundred and fifteen trainee physicians participated. Compared with the 2006 cohort, improvements were seen in 9 of 17 knowledge-based questions and overall score improved in the 2013 cohort. Nonetheless, significant deficits in knowledge, particularly for the diagnostic criteria for delirium, remained. Conclusions: despite improvements in some aspects of delirium knowledge, the diagnostic criteria for delirium remain poorly understood. Challenges remain in ensuring adequate training for junior doctors in delirium. [ABSTRACT FROM AUTHOR]

Context Delirium often presents difficult management challenges in the context of goals of care in palliative care settings. Objectives The aim was to formulate an analytical framework for further research on delirium in palliative care settings, prioritize the associated research questions, discuss the inherent methodological challenges associated with relevant studies, and outline the next steps in a program of delirium research. Methods We combined multidisciplinary input from delirium researchers and knowledge users at an international delirium study planning meeting, relevant literature searches, focused input of epidemiologic expertise, and a meeting participant and coauthor survey to formulate a conceptual research framework and prioritize research questions. Results Our proposed framework incorporates three main groups of research questions: the first was predominantly epidemiologic, such as delirium occurrence rates, risk factor evaluation, screening, and diagnosis; the second covers pragmatic management questions; and the third relates to the development of predictive models for delirium outcomes. Based on aggregated survey responses to each research question or domain, the combined modal ratings of "very" or "extremely" important confirmed their priority. Conclusion Using an analytical framework to represent the full clinical care pathway of delirium in palliative care settings, we identified multiple knowledge gaps in relation to the occurrence rates, assessment, management, and outcome prediction of delirium in this population. The knowledge synthesis generated from adequately powered, multicenter studies to answer the framework's research questions will inform decision making and policy development regarding delirium detection and management and thus help to achieve better outcomes for patients in palliative care settings. [ABSTRACT FROM AUTHOR]

Background: In the general population, the epidemiological relationships between delirium and adverse outcomes are not well defined. The aims of this study were to: (1) construct an algorithm for the diagnosis of delirium using the Geriatric Mental State (GMS) examination; (2) test the criterion validity of this algorithm against mortality and dementia risk; (3) report the age-specific prevalence of delirium as determined by this algorithm.Methods: Participant and informant data in a randomly weighted subsample of the Cognitive Function and Ageing Study were taken from a standardized assessment battery. The algorithmic definition of delirium was based on the DSM-IV classification. Outcomes were: proportional hazard ratios for death; odds ratios of dementia at 2-year follow-up.Results: Data from 2197 persons (representative of 13,004) were used, median age 77 years, 64% women. Study-defined delirium was associated with a new dementia diagnosis at two years (OR 8.82, 95% CI 2.76 to 28.2) and death (HR 1.28, 95% CI 1.03 to 1.60), even after adjustment for acute illness severity. Similar associations were seen for study-defined subsyndromal delirium. Age-specific prevalence as determined by the algorithm increased with age from 1.8% in the 65-69 year age group to 10.1% in the ≥85 age group (p < 0.01 for trend). For study-defined subsyndromal delirium, age-specific period prevalence ranged from 8.2% (65-69 years) to 36.1% (≥85 years).Conclusions: These results demonstrate the possibility of constructing an algorithmic diagnosis for study-defined delirium using data from the GMS schedule, with predictive criterion validity for mortality and dementia risk. These are the first population-based analyses able to account prospectively for both illness severity and an earlier study diagnosis of dementia. [ABSTRACT FROM AUTHOR]

Context Delirium is a highly prevalent complication in patients in palliative care settings, especially in the end-of-life context. Objectives To review the current evidence base for treating episodes of delirium in palliative care settings and propose a framework for future development. Methods We combined multidisciplinary input from delirium researchers and other purposely selected stakeholders at an international delirium study planning meeting. This was supplemented by a literature search of multiple databases and relevant reference lists to identify studies regarding therapeutic interventions for delirium. Results The context of delirium management in palliative care is highly variable. The standard management of a delirium episode includes the investigation of precipitating and aggravating factors followed by symptomatic treatment with drug therapy. However, the intensity of this management depends on illness trajectory and goals of care in addition to the local availability of both investigative modalities and therapeutic interventions. Pharmacologically, haloperidol remains the practice standard by consensus for symptomatic control. Dosing schedules are derived from expert opinion and various clinical practice guidelines as evidence-based data from palliative care settings are limited. The commonly used pharmacologic interventions for delirium in this population warrant evaluation in clinical trials to examine dosing and titration regimens, different routes of administration, and safety and efficacy compared with placebo. Conclusion Delirium treatment is multidimensional and includes the identification of precipitating and aggravating factors. For symptomatic management, haloperidol remains the practice standard. Further high-quality collaborative research investigating the appropriate treatment of this complex syndrome is needed. [ABSTRACT FROM AUTHOR]

Context Delirium occurs in patients across a wide array of health care settings. The extent to which formal management guidelines exist or are adaptable to palliative care is unclear. Objectives This review aims to 1) source published delirium management guidelines with potential relevance to palliative care settings, 2) discuss the process of guideline development, 3) appraise their clinical utility, and 4) outline the processes of their implementation and evaluation and make recommendations for future guideline development. Methods We searched PubMed (1990-2013), Scopus, U.S. National Guideline Clearinghouse, Google, and relevant reference lists to identify published guidelines for the management of delirium. This was supplemented with multidisciplinary input from delirium researchers and other relevant stakeholders at an international delirium study planning meeting. Results There is a paucity of high-level evidence for pharmacological and non-pharmacological interventions in the management of delirium in palliative care. However, multiple delirium guidelines for clinical practice have been developed, with recommendations derived from "expert opinion" for areas where research evidence is lacking. In addition to their potential benefits, limitations of clinical guidelines warrant consideration. Guidelines should be appraised and then adapted for use in a particular setting before implementation. Further research is needed on the evaluation of guidelines, as disseminated and implemented in a clinical setting, focusing on measurable outcomes in addition to their impact on quality of care. Conclusion Delirium clinical guidelines are available but the level of evidence is limited. More robust evidence is required for future guideline development. [ABSTRACT FROM AUTHOR]

Delirium is a common and acute neurocognitive disorder in older adults associated with increased risk of dementia and death. Understanding the interaction between brain vulnerability and acute stressors is key to delirium pathophysiology, but the neurophysiology of delirium vulnerability is not well defined. This study aimed to identify pre-operative resting-state EEG and event-related potential markers of incident delirium and its subtypes in older adults undergoing elective cardiac procedures. This prospective observational study included 58 older participants (mean age = 75.6 years, SD = 7.1; 46 male/12 female); COVID-19 restrictions limited recruitment. Baseline assessments were conducted in the weeks before elective cardiac procedures and included a 4-min resting-state EEG recording (2-min eyes open and 2-min eyes closed), a 5-min frequency auditory oddball paradigm recording, and cognitive and depression examinations. Periodic peak power, peak frequency and bandwidth measures, and aperiodic offsets and exponents were derived from resting-state EEG data. Event-related potentials were measured as mean component amplitudes (first positive component, first negative component, early third positive component, and mismatch negativity) following standard and deviant auditory stimuli. Incident delirium occurred in 21 participants: 10 hypoactive, 6 mixed, and 5 hyperactive. Incident hyperactive delirium was associated with higher pre-operative eyes open ( P = 0.045, d = 1.0) and closed ( P = 0.036, d = 1.0) aperiodic offsets. Incident mixed delirium was associated with significantly larger pre-operative first positive component amplitudes to deviants ( P = 0.037, d = 1.0) and larger third positive component amplitudes to standards ( P = 0.025, d = 1.0) and deviants ( P = 0.041, d = 0.9). Other statistically non-significant but moderate-to-large effects were observed in relation to all subtypes. We report evidence of neurophysiological markers of delirium risk weeks prior to elective cardiac procedures in older adults. Despite being underpowered due to COVID-19-related recruitment impacts, these findings indicate pre-operative dysfunction in neural excitation/inhibition balance associated with different delirium subtypes and warrant further investigation on a larger scale., Competing Interests: The authors report no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: Dementia is a progressive syndrome of global cognitive impairment with significant health and social care costs. Global prevalence is projected to increase, particularly in resource-limited settings. Recent policy changes in Western countries to increase detection mandates a careful examination of the diagnostic accuracy of neuropsychological tests for dementia., Objectives: To determine the diagnostic accuracy of the Montreal Cognitive Assessment (MoCA) at various thresholds for dementia and its subtypes., Search Methods: We searched MEDLINE, EMBASE, BIOSIS Previews, Science Citation Index, PsycINFO and LILACS databases to August 2012. In addition, we searched specialised sources containing diagnostic studies and reviews, including MEDION (Meta-analyses van Diagnostisch Onderzoek), DARE (Database of Abstracts of Reviews of Effects), HTA (Health Technology Assessment Database), ARIF (Aggressive Research Intelligence Facility) and C-EBLM (International Federation of Clinical Chemistry and Laboratory Medicine Committee for Evidence-based Laboratory Medicine) databases. We also searched ALOIS (Cochrane Dementia and Cognitive Improvement Group specialized register of diagnostic and intervention studies). We identified further relevant studies from the PubMed 'related articles' feature and by tracking key studies in Science Citation Index and Scopus. We also searched for relevant grey literature from the Web of Science Core Collection, including Science Citation Index and Conference Proceedings Citation Index (Thomson Reuters Web of Science), PhD theses and contacted researchers with potential relevant data., Selection Criteria: Cross-sectional designs where all participants were recruited from the same sample were sought; case-control studies were excluded due to high chance of bias. We searched for studies from memory clinics, hospital clinics, primary care and community populations. We excluded studies of early onset dementia, dementia from a secondary cause, or studies where participants were selected on the basis of a specific disease type such as Parkinson's disease or specific settings such as nursing homes., Data Collection and Analysis: We extracted dementia study prevalence and dichotomised test positive/test negative results with thresholds used to diagnose dementia. This allowed calculation of sensitivity and specificity if not already reported in the study. Study authors were contacted where there was insufficient information to complete the 2x2 tables. We performed quality assessment according to the QUADAS-2 criteria.Methodological variation in selected studies precluded quantitative meta-analysis, therefore results from individual studies were presented with a narrative synthesis., Main Results: Seven studies were selected: three in memory clinics, two in hospital clinics, none in primary care and two in population-derived samples. There were 9422 participants in total, but most of studies recruited only small samples, with only one having more than 350 participants. The prevalence of dementia was 22% to 54% in the clinic-based studies, and 5% to 10% in population samples. In the four studies that used the recommended threshold score of 26 or over indicating normal cognition, the MoCA had high sensitivity of 0.94 or more but low specificity of 0.60 or less., Authors' Conclusions: The overall quality and quantity of information is insufficient to make recommendations on the clinical utility of MoCA for detecting dementia in different settings. Further studies that do not recruit participants based on diagnoses already present (case-control design) but apply diagnostic tests and reference standards prospectively are required. Methodological clarity could be improved in subsequent DTA studies of MoCA by reporting findings using recommended guidelines (e.g. STARDdem). Thresholds lower than 26 are likely to be more useful for optimal diagnostic accuracy of MoCA in dementia, but this requires confirmation in further studies.

Objective: to evaluate the performance of the 4 'A's Test (4AT) in screening for delirium in older patients. The 4AT is a new test for rapid screening of delirium in routine clinical practice., Design: : prospective study of consecutively admitted elderly patients with independent 4AT and reference standard assessments., Setting: : an acute geriatrics ward and a department of rehabilitation., Participants: two hundred and thirty-six patients (aged ≥70 years) consecutively admitted over a period of 4 months., Measurements: in each centre, the 4AT was administered by a geriatrician to eligible patients within 24 h of admission. Reference standard delirium diagnosis (DSM-IV-TR criteria) was obtained within 30 min by a different geriatrician who was blind to the 4AT score. The presence of dementia was assessed using the Alzheimer's Questionnaire and the informant section of the Clinical Dementia Rating scale. The main outcome measure was the accuracy of the 4AT in diagnosing delirium., Results: patients were 83.9 ± 6.1 years old, and the majority were women (64%). Delirium was detected in 12.3% (n = 29), dementia in 31.2% (n = 74) and a combination of both in 7.2% (n = 17). The 4AT had a sensitivity of 89.7% and specificity 84.1% for delirium. The areas under the receiver operating characteristic curves for delirium diagnosis were 0.93 in the whole population, 0.92 in patients without dementia and 0.89 in patients with dementia., Conclusions: the 4AT is a sensitive and specific method of screening for delirium in hospitalised older people. Its brevity and simplicity support its use in routine clinical practice., (© The Author 2014. Published by Oxford University Press on behalf of the British Geriatrics Society.)