Neurophysiological patterns reflecting vulnerability to delirium subtypes: a resting-state EEG and event-related potential study.

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.

A Digitally Enabled, Pharmacist service to detecT medicine harms in residential aged care (nursing home) (ADEPT): protocol for a feasibility study.

INTRODUCTION: This feasibility study aims to develop and test a new model of practice in Australia using digital technologies to enable pharmacists to monitor early signs and symptoms of medicine-induced harms in residential aged care. METHODS AND ANALYSIS: Thirty residents will be recruited from an aged care facility in South Australia. The study will be conducted in two phases. In phase I, the study team will work with aged care software providers and developers of digital technologies (a wearable activity tracker and a sleep tracking sensor) to gather physical activity and sleep data, as well as medication and clinical data from the electronic medication management system and aged care clinical software. Data will be centralised into a cloud-based monitoring platform (TeleClinical Care (TCC)). The TCC will be used to create dashboards that will include longitudinal visualisations of changes in residents' health, function and medicine use over time. In phase II, the on-site pharmacist will use the centralised TCC platform to monitor each resident's medicine, clinical, physical activity and sleep data to identify signs of medicine-induced harms over a 12-week period.A mixed methods process evaluation applying the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) evaluation framework will be used to assess the feasibility of the service. Outcome measures include service reach, changes in resident symptom scores (measured using the Edmonton Symptom Assessment System), number of medication adverse events detected, changes in physical activity and sleep, number of pharmacist recommendations provided, cost analysis and proportion of all pharmacists' recommendations implemented at 4-week, 8-week and 12-week postbaseline period. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the University of South Australia's Human Research Ethics Committee (205098). Findings will be disseminated through published manuscripts, conference presentations and reporting to the study funder. TRIAL REGISTRATION NUMBER: ACTRN12623000506695.

How do predisposing factors differ between delirium motor subtypes? A systematic review and meta-analysis.

BACKGROUND: Delirium is a common neurocognitive disorder in hospitalised older adults with vast negative consequences. The predominant method of subtyping delirium is by motor activity profile into hypoactive, hyperactive and mixed groups. OBJECTIVE: This systematic review and meta-analysis investigated how predisposing factors differ between delirium motor subtypes. METHODS: Databases (Medline, PsycINFO, Embase) were systematically searched for studies reporting predisposing factors (prior to delirium) for delirium motor subtypes. A total of 61 studies met inclusion criteria (N = 14,407, mean age 73.63 years). Random-effects meta-analyses synthesised differences between delirium motor subtypes relative to 22 factors. RESULTS: Hypoactive cases were older, had poorer cognition and higher physical risk scores than hyperactive cases and were more likely to be women, living in care homes, taking more medications, with worse functional performance and history of cerebrovascular disease than all remaining subtypes. Hyperactive cases were younger than hypoactive and mixed subtypes and were more likely to be men, with better cognition and lower physical risk scores than all other subtypes. Those with no motor subtype (unable to be classified) were more likely to be women and have better functional performance. Effect sizes were small. CONCLUSIONS: Important differences in those who develop motor subtypes of delirium were shown prior to delirium occurrence. We provide robust quantitative evidence for a common clinical assumption that indices of frailty (institutional living, cognitive and functional impairment) are seen more in hypoactive patients. Motor subtypes should be measured across delirium research. Motor subtyping has great potential to improve the clinical risk assessment and management of delirium.

The neuropsychological profile of delirium vulnerability: A systematic review and meta-analysis.

Delirium is a common neurocognitive disorder in hospitalised older adults with substantial negative consequences. Impaired global cognition is a well-established delirium risk factor. However, poor performance on attention tests and higher intra-subject variability may be more sensitive delirium risk factors, given the disorder is characterised by a fluctuating course and attentional deficits. We systematically searched databases (Embase, PsycINFO, MEDLINE) and 44 studies satisfied inclusion criteria. Random-effects meta-analysis models showed poor performance in all cognitive domains except perception was significantly associated with incident delirium. Largest effects were for orientation (g=-1.20) and construction and motor performance (g=-0.60). These effects were no longer significant in the subgroup without pre-existing cognitive impairment, where executive functions and verbal functions and language skills were associated with incident delirium. A small, non-significant association between intra-subject variability and incident delirium was found (g=0.42). Cognitive domain specific tests may be quicker and more sensitive predictors of incident delirium. This pattern of neuropsychological findings supports the proposition that vulnerability for delirium manifests as a dysfunction of whole-brain information integration.

DelIrium VULnerability in GEriatrics (DIVULGE) study: a protocol for a prospective observational study of electroencephalogram associations with incident postoperative delirium.

INTRODUCTION: Delirium is a neurocognitive disorder common in older adults in acute care settings. Those who develop delirium are at an increased risk of dementia, cognitive decline and death. Electroencephalography (EEG) during delirium in older adults is characterised by slowing and reduced functional connectivity, but markers of vulnerability are poorly described. We aim to identify EEG spectral power and event-related potential (ERP) markers of incident delirium in older adults to understand neural mechanisms of delirium vulnerability. Characterising delirium vulnerability will provide substantial theoretical advances and outcomes have the potential to be translated into delirium risk assessment tools. METHODS AND ANALYSIS: We will record EEG in 90 participants over 65 years of age prior to elective coronary artery bypass grafting (CABG) or transcatheter aortic valve implantation (TAVI). We will record 4-minutes of resting state (eyes open and eyes closed) and a 5-minute frequency auditory oddball paradigm. Outcome measures will include frequency band power, 1/f offset and slope, and ERP amplitude measures. Participants will undergo cognitive and EEG testing before their elective procedures and daily postoperative delirium assessments. Group allocation will be done retrospectively by linking preoperative EEG data according to postoperative delirium status (presence, severity, duration and subtype). ETHICS AND DISSEMINATION: This study is approved by the Human Research Ethics Committee of the Royal Adelaide Hospital, Central Adelaide Local Health Network and the University of South Australia Human Ethics Committee. Findings will be disseminated through peer-reviewed journal articles and presentations at national and international conferences. TRIAL REGISTRATION NUMBER: ACTRN12618001114235 and ACTRN12618000799257.

Investigating how electroencephalogram measures associate with delirium: A systematic review.

Delirium is a common neurocognitive disorder in hospital settings, characterised by fluctuating impairments in attention and arousal following an acute precipitant. Electroencephalography (EEG) is a useful method to understand delirium pathophysiology. We performed a systematic review to investigate associations between delirium and EEG measures recorded prior, during, and after delirium. A total of 1,655 articles were identified using PsycINFO, Embase and MEDLINE, 31 of which satisfied inclusion criteria. Methodological quality assessment was undertaken, resulting in a mean quality score of 4 out of a maximum of 5. Qualitative synthesis revealed EEG slowing and reduced functional connectivity discriminated between those with and without delirium (i.e. EEG during delirium); the opposite pattern was apparent in children, with cortical hyperexcitability. EEG appears to have utility in differentiating those with and without delirium, but delirium vulnerability and the long-term effects on brain function require further investigation. Findings provide empirical support for the theory that delirium is a disorder of reduced functional brain integration.

Cognitive outcomes following coronary artery bypass grafting: A systematic review and meta-analysis of 91,829 patients.

BACKGROUND: Cognitive impairments, including delirium, are common after coronary artery bypass grafting (CABG) surgery, as described in over three decades of research. Our aim was to pool estimates across the literature for the first-time, relative to time (from pre- to post-CABG) and diagnosis (cognitive impairment, delirium and dementia). METHODS: A systematic search of four databases was undertaken. 215 studies incorporating data from 91,829 patients were used to estimate the prevalence of cognitive impairments pre- and post-CABG, including delirium and dementia post-CABG, using random effects meta-analyses. RESULTS: Pre-surgical cognitive impairment was seen in 19% of patients. Post-operatively, cognitive impairment was seen in around 43% of patients acutely; this resolved to 19% at 4-6 months and then increased to 25% of patients between 6-months to 1-year post-operatively. In the long term, between 1 and 5-years post-operatively, cognitive impairment increased and was seen in nearly 40% of patients. Post-operative delirium was apparent in 18% of CABG patients which increased to 24% when a diagnostic instrument was utilized alongside clinical criteria. Dementia was present in 7% of patients 5-7 years post-surgery. CONCLUSION: The results of this meta-analysis demonstrate that cognitive impairment and delirium are major issues in CABG patients which require specific attention. It is imperative that appropriate methods for investigating cognitive impairment, and screening for delirium using a diagnostic instrument, occur in both pre-and post-CABG settings.