A systematic review of studies reporting on neuropsychological and functional domains used for assessment of recovery from delirium in acute hospital patients.

OBJECTIVES: Assessing for recovery in delirium is essential in guiding ongoing investigation and treatment. Yet, there is little scrutiny and no research or clinical consensus on how recovery should be measured. We reviewed studies which used tests of neuropsychological domains and functional ability to track recovery of delirium longitudinally in acute hospital settings. METHODS/DESIGN: We systematically searched databases (MEDLINE, PsycInfo, CINAHL, Embase, ClinicalTrials.gov, Cochrane Central Register of Controlled Trials), from inception to October 14th , 2022. Inclusion criteria were: adult acute hospital patients (≥18 years) diagnosed with delirium by a validated tool; 1+ repeat assessment using an assessment tool measuring domains of delirium/functional recovery ≤7 days from baseline. Two reviewers independently screened articles, performed data extraction, and assessed risk of bias. A narrative data synthesis was completed. RESULTS: From 6533 screened citations, we included 39 papers (reporting 32 studies), with 2370 participants with delirium. Studies reported 21 tools with an average of four repeat assessments including baseline (range 2-10 assessments within ≤7 days), measuring 15 specific domains. General cognition, functional ability, arousal, attention and psychotic features were most commonly assessed for longitudinal change. Risk of bias was moderate to high for most studies. CONCLUSIONS: There was no standard approach for tracking change in specific domains of delirium. The methodological heterogeneity of studies was too high to draw firm conclusions on the effectiveness of assessment tools to measure delirium recovery. This highlights the need for standardised methods for assessing recovery from delirium.

Three key areas in progressing delirium practice and knowledge: recognition and relief of distress, new directions in delirium epidemiology and developing better research assessments.

Delirium presents formidable challenges: it affects one in four of older hospitalised adults, greatly elevates the risk of multiple short- and long-term complications including dementia and causes significant distress. Delirium care remains generally poor. Yet, there are clear grounds for optimism; the last decade has seen impactful policy advances and a tripling of research output. Here, we highlight three linked areas which have strong potential to transform delirium practice and knowledge in the near term. Delirium-related distress is strikingly underrepresented in practice guidance and research. Proactive recognition combined with effective clinical responses based on good communication provides a critical and largely untapped opportunity to improve care. Delirium epidemiology research is well positioned to produce novel insights through advanced prospective designs in populations such as emergency medical patients with detailed pre-, intra- and post-delirium assessments allied with fluid, imaging and other biomarkers. Research-grade assessment of delirium currently involves a chaotic array of tools, methods and diagnostic algorithms. Areas for development: expand and analytically distinguish the range of features assessed (including distress), optimise feature assessment including use of validated neuropsychological tests where possible, produce standardised algorithms which articulate explicit pathways from features to diagnosis, and create new fine-grained approaches to the measurement of severity. Delirium practice and knowledge show accelerating growth. This is encouraging but much of the necessary progress is still to come. Innovation in these three highlighted areas, as well as many others, will open up exciting possibilities in enhancing the care of patients with this common and often devastating condition.

Straight and Divergent Pathways to Cognitive State: Seven Decades of Follow-Up in the British 1946 Birth Cohort.

BACKGROUND: Using the British 1946 birth cohort we previously estimated life course paths to the Addenbrooke's Cognitive Examination (ACE-III). OBJECTIVE: We now compared those whose ACE-III scores were expected, worse and better than predicted from the path model on a range of independent variables including clinical ratings of cognitive impairment and neuroimaging measures. METHODS: Predicted ACE-III scores were categorized into three groups: those with Expected (between -1.5 and 1.5 standard deviation; SD); Worse (< -1.5 SD); and Better (>1.5 SD) scores. Differences in the independent variables were then tested between these three groups. RESULTS: Compared with the Expected group, those in the Worse group showed independent evidence of progressive cognitive impairment: faster memory decline, more self-reported memory difficulties, more functional difficulties, greater likelihood of being independently rated by experienced specialist clinicians as having a progressive cognitive impairment, and a cortical thinning pattern suggestive of preclinical Alzheimer's disease. Those in the Better group showed slower verbal memory decline and absence of independently rated progressive cognitive impairment compared to the Expected group, but no differences in any of the other independent variables including the neuroimaging variables. CONCLUSION: The residual approach shows that life course features can map directly to clinical diagnoses. One future challenge is to translate this into a readily usable algorithm to identify high-risk individuals in preclinical state, when preventive strategies and therapeutic interventions may be most effective.

Associations of Word Memory, Verbal Fluency, Processing Speed, and Crystallized Cognitive Ability With One-Legged Balance Performance in Mid- and Later Life.

BACKGROUND: Cognitive integration of sensory input and motor output plays an important role in balance. Despite this, it is not clear if specific cognitive processes are associated with balance and how these associations change with age. We examined longitudinal associations of word memory, verbal fluency, search speed, and reading ability with repeated measures of one-legged balance performance. METHOD: Up to 2 934 participants in the MRC National Survey of Health and Development, a British birth cohort study, were included. At age 53, word memory, verbal fluency, search speed, and reading ability were assessed. One-legged balance times (eyes closed) were measured at ages 53, 60-64, and 69 years. Associations between each cognitive measure and balance time were assessed using random-effects models. Adjustments were made for sex, death, attrition, height, body mass index, health conditions, health behaviors, education, and occupational class. RESULTS: In sex-adjusted models, 1 SD higher scores in word memory, search speed, and verbal fluency were associated with 14.1% (95% CI: 11.3, 16.8), 7.2% (4.4, 9.9), and 10.3% (7.5, 13.0) better balance times at age 53, respectively. Higher reading scores were associated with better balance, although this association plateaued. Associations were partially attenuated in mutually adjusted models and effect sizes were smaller at ages 60-64 and 69. In fully adjusted models, associations were largely explained by education, although remained for word memory and search speed. CONCLUSIONS: Higher cognitive performance across all measures was independently associated with better balance performance in midlife. Identification of individual cognitive mechanisms involved in balance could lead to opportunities for targeted interventions in midlife.

Prognostic accuracy of the one-legged balance test in predicting falls: 15-years of midlife follow-up in a British birth cohort study.

Introduction: The one-legged balance test is a common screening tool for fall risk. Yet, there is little empirical evidence assessing its prognostic ability. The study aims were to assess the prognostic accuracy of one-legged balance performance in predicting falls and identify optimal cut-points to classify those at greater risk. Methods: Data from up to 2,000 participants from a British birth cohort born in 1,946 were used. The times an individual could stand on one leg with their eyes open and closed were recorded (max: 30 s) at ages 53 and 60-64. Number of falls in the past year was self-reported at ages 53, 60-64 and 68; recurrent falls (0-1 vs. 2+) and any fall (0 vs. 1+) were considered binary outcomes. Four longitudinal associations between balance times and subsequent falls were investigated (age 53 → 60-64; age 53 → 68; age 60-64 → 68; age 53 & 60-64 → 68). For each temporal association, areas under the curve (AUC) were calculated and compared for a base sex-only model, a sex and balance model, a sex and fall history model and a combined model of sex, balance and fall history. The Liu method was used to identify optimal cut-points and sensitivity, specificity, and AUC at corresponding cut-points. Results: Median eyes open balance time was 30 s at ages 53 and 60-64; median eyes closed balance times were 5 s and 3 s, respectively. The predictive ability of balance tests in predicting either fall outcome was poor (AUC range for sex and balance models: 0.577-0.600). Prognostic accuracy consistently improved by adding fall history to the model (range: 0.604-0.634). Optimal cut-points ranged from 27 s to 29 s for eyes open and 3 s to 5 s for eyes closed; AUC consistently indicated that using "optimal" cut-points to dichotomise balance time provided no discriminatory ability (AUC range:0.42-0.47), poor sensitivity (0.38-0.61) and poor specificity (0.23-0.56). Discussion: Despite previous observational evidence showing associations between better one-legged balance performance and reduced fall risk, the one-legged balance test had limited prognostic accuracy in predicting recurrent falls. This contradicts ongoing translation of this test into clinical screening tools for falls and highlights the need to consider new and existing screening tools that can reliably predict fall risk.

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.

Hospitalisation without delirium is not associated with cognitive decline in a population-based sample of older people-results from a nested, longitudinal cohort study.

BACKGROUND: Acute hospitalisation and delirium have individually been shown to adversely affect trajectories of cognitive decline but have not previously been considered together. This work aimed to explore the impact on cognition of hospital admission with and without delirium, compared to a control group with no hospital admissions. METHODS: The Delirium and Cognitive Impact in Dementia (DECIDE) study was nested within the Cognitive Function and Ageing Study II (CFAS II)-Newcastle cohort. CFAS II participants completed two baseline interviews, including the Mini-Mental State Examination (MMSE). During 2016, surviving participants from CFAS II-Newcastle were recruited to DECIDE on admission to hospital. Participants were reviewed daily to determine delirium status.During 2017, all DECIDE participants and age, sex and years of education matched controls without hospital admissions during 2016 were invited to repeat the CFAS II interview. Delirium was excluded in the control group using the Informant Assessment of Geriatric Delirium Scale (i-AGeD). Linear mixed effects modelling determined predictors of cognitive decline. RESULTS: During 2016, 82 of 205 (40%) DECIDE participants had at least one episode of delirium. At 1 year, 135 of 205 hospitalised participants completed an interview along with 100 controls. No controls experienced delirium (i-AGeD>4). Delirium was associated with a faster rate of cognitive decline compared to those without delirium (ß = -2.2, P < 0.001), but number of hospital admissions was not (P = 0.447). CONCLUSIONS: These results suggest that delirium during hospitalisation rather than hospitalisation per se is a risk factor for future cognitive decline, emphasising the need for dementia prevention studies that focus on delirium intervention.

Early-Life Socioeconomic Position and the Accumulation of Health-Related Deficits by Midlife in the 1958 British Birth Cohort Study.

Reducing population levels of frailty is an important goal, and preventing its development in midadulthood could be pivotal. There is limited evidence on associations between childhood socioeconomic position (SEP) and frailty. Using data on the 1958 British birth cohort (followed from 1958 to 2016; n = 8,711), we aimed to 1) establish the utility of measuring frailty in midlife, by examining associations between a 34-item frailty index at age 50 years (FI50y) and mortality at ages 50-58 years, and 2) examine associations between early-life SEP and FI50y and investigate whether these associations were explained by adult SEP. Hazard ratios for mortality increased with increasing frailty; for example, the sex-adjusted hazard ratio for the highest quintile of FI50y versus the lowest was 4.07 (95% confidence interval (CI): 2.64, 6.25). Lower early-life SEP was associated with higher FI50y. Compared with participants born in the highest social class, the estimated total effect on FI50y was 42.0% (95% CI: 35.5, 48.4) for participants born in the lowest class, with the proportion mediated by adult SEP being 0.45% (95% CI: 0.35, 0.55). Mediation by adult SEP was negligible for other early-life SEP classes. Findings suggest that early-life SEP is associated with frailty and that adult SEP only partially explains this association. Results highlight the importance of improving socioeconomic circumstances across the life course to reduce inequalities in midlife frailty.

Recurrent delirium over 12 months predicts dementia: results of the Delirium and Cognitive Impact in Dementia (DECIDE) study.

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.

Bidirectional associations between word memory and one-legged balance performance in mid and later life.

BACKGROUND: Age-related changes in cognitive and balance capabilities are well-established, as is their correlation with one another. Given limited evidence regarding the directionality of associations, we aimed to explore the direction and potential explanations of associations between word memory and one-legged balance performance in mid-later life. METHODS: A total of 3062 participants in the Medical Research Council National Survey of Health and Development, a British birth cohort study, were included. One-legged balance times (eyes closed) were measured at ages 53, 60-64 and 69 years. Word memory was assessed at ages 43, 53, 60-64 and 69 with three 15-item word-recall trials. Autoregressive cross-lagged and dual change score models assessed bidirectional associations between word memory and balance. Random-effects models quantified the extent to which these associations were explained by adjustment for anthropometric, socioeconomic, behavioural and health status indicators. RESULTS: Autoregressive cross-lagged and dual change score models suggested a unidirectional association between word memory and subsequent balance performance. In a sex-adjusted random-effects model, 1 standard deviation increase in word memory was associated with 9% (7,12%) higher balance performance at age 53. This association decreased with age (-0.4% /year (-0.6,-0.1%). Education partially attenuated the association, although it remained in the fully-adjusted model (3% (0.1,6%)). CONCLUSIONS: There was consistent evidence that word memory is associated with subsequent balance performance but no evidence of the reverse association. Cognitive processing plays an important role in the balance process, with educational attainment providing some contribution. These findings have important implications for understanding cognitive-motor associations and for interventions aimed at improving cognitive and physical capability in the ageing population.

Risk Factors for Delirium and Cognitive Decline Following Coronary Artery Bypass Grafting Surgery: A Systematic Review and Meta-Analysis.

Background Coronary artery bypass grafting (CABG) is known to improve heart function and quality of life, while rates of surgery-related mortality are low. However, delirium and cognitive decline are common complications. We sought to identify preoperative, intraoperative, and postoperative risk or protective factors associated with delirium and cognitive decline (across time) in patients undergoing CABG. Methods and Results We conducted a systematic search of Medline, PsycINFO, EMBASE, and Cochrane (March 26, 2019) for peer-reviewed, English publications reporting post-CABG delirium or cognitive decline data, for at least one risk factor. Random-effects meta-analyses estimated pooled odds ratio for categorical data and mean difference or standardized mean difference for continuous data. Ninety-seven studies, comprising data from 60 479 patients who underwent CABG, were included. Moderate to large and statistically significant risk factors for delirium were as follows: (1) preoperative cognitive impairment, depression, stroke history, and higher European System for Cardiac Operative Risk Evaluation (EuroSCORE) score, (2) intraoperative increase in intubation time, and (3) postoperative presence of arrythmia and increased days in the intensive care unit; higher preoperative cognitive performance was protective for delirium. Moderate to large and statistically significant risk factors for acute cognitive decline were as follows: (1) preoperative depression and older age, (2) intraoperative increase in intubation time, and (3) postoperative presence of delirium and increased days in the intensive care unit. Presence of depression preoperatively was a moderate risk factor for midterm (1-6 months) post-CABG cognitive decline. Conclusions This meta-analysis identified several key risk factors for delirium and cognitive decline following CABG, most of which are nonmodifiable. Future research should target preoperative risk factors, such as depression or cognitive impairment, which are potentially modifiable. Registration URL: https://www.crd.york.ac.uk/prosp​ero/; Unique identifier: CRD42020149276.

Associations Between Factors Across Life and One-Legged Balance Performance in Mid and Later Life: Evidence From a British Birth Cohort Study.

INTRODUCTION: Despite its associations with falls, disability, and mortality, balance is an under-recognized and frequently overlooked aspect of aging. Studies investigating associations between factors across life and balance are limited. Understanding the factors related to balance performance could help identify protective factors and appropriate interventions across the life course. This study aimed to: (i) identify socioeconomic, anthropometric, behavioral, health, and cognitive factors that are associated with one-legged balance performance; and (ii) explore how these associations change with age. METHODS: Data came from 3,111 members of the MRC National Survey of Health and Development, a British birth cohort study. Multilevel models examined how one-legged standing balance times (assessed at ages 53, 60-64, and 69) were associated with 15 factors across life: sex, maternal education (4 years), paternal occupation (4 years), own education (26 years), own occupation (53 years), and contemporaneous measures (53, 60-64, 69 years) of height, BMI, physical activity, smoking, diabetes, respiratory symptoms, cardiovascular events, knee pain, depression and verbal memory. Age and sex interactions with each variable were assessed. RESULTS: Men had 18.8% (95%CI: 13.6, 23.9) longer balance times than women at age 53, although this difference decreased with age (11.8% at age 60-64 and 7.6% at age 69). Disadvantaged socioeconomic position in childhood and adulthood, low educational attainment, less healthy behaviors, poor health status, lower cognition, higher body mass index (BMI), and shorter height were associated with poorer balance at all three ages. For example, at age 53, those from the lowest paternal occupational classes had 29.6% (22.2, 38.8) worse balance than those from the highest classes. Associations of balance with socioeconomic indicators, cognition and physical activity became smaller with age, while associations with knee pain and depression became larger. There were no sex differences in these associations. In a combined model, the majority of factors remained associated with balance. DISCUSSION: This study identified numerous risk factors across life that are associated with one-legged balance performance and highlighted diverse patterns of association with age, suggesting that there are opportunities to intervene in early, mid and later life. A multifactorial approach to intervention, at both societal and individual levels, may have more benefit than focusing on a single risk factor.

The Dementias Platform UK (DPUK) Data Portal.

The Dementias Platform UK Data Portal is a data repository facilitating access to data for 3 370 929 individuals in 42 cohorts. The Data Portal is an end-to-end data management solution providing a secure, fully auditable, remote access environment for the analysis of cohort data. All projects utilising the data are by default collaborations with the cohort research teams generating the data. The Data Portal uses UK Secure eResearch Platform infrastructure to provide three core utilities: data discovery, access, and analysis. These are delivered using a 7 layered architecture comprising: data ingestion, data curation, platform interoperability, data discovery, access brokerage, data analysis and knowledge preservation. Automated, streamlined, and standardised procedures reduce the administrative burden for all stakeholders, particularly for requests involving multiple independent datasets, where a single request may be forwarded to multiple data controllers. Researchers are provided with their own secure 'lab' using VMware which is accessed using two factor authentication. Over the last 2 years, 160 project proposals involving 579 individual cohort data access requests were received. These were received from 268 applicants spanning 72 institutions (56 academic, 13 commercial, 3 government) in 16 countries with 84 requests involving multiple cohorts. Projects are varied including multi-modal, machine learning, and Mendelian randomisation analyses. Data access is usually free at point of use although a small number of cohorts require a data access fee.

Computerised cognitive training to improve cognition including delirium following coronary artery bypass grafting surgery: protocol for a blinded randomised controlled trial.

INTRODUCTION: Coronary artery bypass grafting (CABG) surgery is known to improve vascular function and cardiac-related mortality rates; however, it is associated with high rates of postoperative cognitive decline and delirium. Previous attempts to prevent post-CABG cognitive decline using pharmacological and surgical approaches have been largely unsuccessful. Cognitive prehabilitation and rehabilitation are a viable yet untested option for CABG patients. We aim to investigate the effects of preoperative cognitive training on delirium incidence, and preoperative and postoperative cognitive training on cognitive decline at 4 months post-CABG. METHODS AND ANALYSIS: This study is a randomised, single-blinded, controlled trial investigating the use of computerised cognitive training (CCT) both pre-CABG and post-CABG (intervention group) compared with usual care (control group) in older adults undergoing CABG in Adelaide, South Australia. Those in the intervention group will complete 1-2 weeks of CCT preoperatively (45-60 min sessions, 3.5 sessions/week) and 12 weeks of CCT postoperatively (commencing 1 month following surgery, 45-60 min sessions, 3 sessions/week). All participants will undergo cognitive testing preoperatively, over their hospital stay including delirium, and postoperatively for up to 1 year. The primary delirium outcome variable will be delirium incidence (presence vs absence); the primary cognitive decline variable will be at 4 months (significant decline vs no significant decline/improvement from baseline). Logistic regression modelling will be used, with age and gender as covariates. Secondary outcomes include cognitive decline from baseline to discharge, and at 6 months and 1 year post-CABG. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Central Adelaide Local Health Network Human Research Ethics Committee (South Australia, Australia) and the University of South Australia Human Ethics Committee, with original approval obtained on 13 December 2017. It is anticipated that approximately two to four publications and multiple conference presentations (national and international) will result from this research. TRIAL REGISTRATION NUMBER: This clinical trial is registered with the Australian New Zealand Clinical Trials Registry and relates to the pre-results stage. Registration number: ACTRN12618000799257.

Childhood Cognition and Age-Related Change in Standing Balance Performance From Mid to Later Life: Findings From a British Birth Cohort.

BACKGROUND: Cognitive processing plays a crucial role in the integration of sensory input and motor output that facilitates balance. However, whether balance ability in adulthood is influenced by cognitive pathways established in childhood is unclear, especially as no study has examined if these relationships change with age. We aimed to investigate associations between childhood cognition and age-related change in standing balance between mid and later life. METHODS: Data on 2,380 participants from the MRC National Survey of Health and Development were included in analyses. Repeated measures multilevel models estimated the association between childhood cognition, assessed at age 15, and log-transformed balance time, assessed at ages 53, 60-64, and 69 using the one-legged stand with eyes closed. Adjustments were made for sex, death, attrition, anthropometric measures, health conditions, health behaviors, education, other indicators of socioeconomic position (SEP), and adult verbal memory. RESULTS: In a sex-adjusted model, 1 standard deviation increase in childhood cognition was associated with a 13% (95% confidence interval: 10, 16; p < .001) increase in balance time at age 53, and this association got smaller with age (cognition × age interaction: p < .001). Adjustments for education, adult verbal memory, and SEP largely explained these associations. CONCLUSIONS: Higher childhood cognition was associated with better balance performance in midlife, with diminishing associations with increasing age. The impact of adjustment for education, cognition and other indicators of SEP suggested a common pathway through which cognition is associated with balance across life. Further research is needed to understand underlying mechanisms, which may have important implications for falls risk and maintenance of physical capability.

Identifying the lifetime cognitive and socioeconomic antecedents of cognitive state: seven decades of follow-up in a British birth cohort study.

OBJECTIVES: The life course determinants of midlife and later life cognitive function have been studied using longitudinal population-based cohort data, but far less is known about whether the pattern of these pathways is similar or distinct for clinically relevant cognitive state. We investigated this for Addenbrooke's Cognitive Examination third edition (ACE-III), used in clinical settings to screen for cognitive impairment and dementia. DESIGN: Longitudinal birth cohort study. SETTING: Residential addresses in England, Wales and Scotland. PARTICIPANTS: 1762 community-dwelling men and women of European heritage, enrolled since birth in the Medical Research Council (MRC) National Survey of Health and Development (the British 1946 birth cohort). PRIMARY OUTCOME: ACE-III. RESULTS: Path modelling estimated direct and indirect associations between apolipoprotein E (APOE) status, father's social class, childhood cognition, education, midlife occupational complexity, midlife verbal ability (National Adult Reading Test; NART), and the total ACE-III score. Controlling for sex, there was a direct negative association between APOE ε4 and the ACE-III score (ß=-0.04 [-0.08 to -0.002], p=0.04), but not between APOE ε4 and childhood cognition (ß=0.03 [-0.006 to 0.069], p=0.10) or the NART (ß=0.0005 [-0.03 to 0.03], p=0.97). The strongest influences on the ACE-III were from childhood cognition (ß=0.20 [0.14 to 0.26], p<0.001) and the NART (ß=0.35 [0.29 to 0.41], p<0.001); educational attainment and occupational complexity were modestly and independently associated with the ACE-III (ß=0.08 [0.03 to 0.14], p=0.002 and ß=0.05 [0.01 to 0.10], p=0.02, respectively). CONCLUSIONS: The ACE-III in the general population shows a pattern of life course antecedents that is similar to neuropsychological measures of cognitive function, and may be used to represent normal cognitive ageing as well as a screen for cognitive impairment and dementia.

Impairments in balance and mobility identify delirium in patients with comorbid dementia.

ABSTRACTDiagnosing delirium superimposed on dementia (DSD) remains challenging because of a lack of specific tools, though motor dysfunction in delirium has been relatively under-explored. This study aimed to use dysfunction in balance and mobility (with the Hierarchical Assessment of Balance And Mobility: HABAM) to identify DSD. This is a cross-sectional multicenter study, recruiting consecutive patients ≥70 years admitted to five acute or rehabilitation hospitals in Ireland, Italy, Portugal, and Switzerland. Delirium was diagnosed using DSM-5 criteria; dementia was determined by the Mini-Mental State Examination and the Questionnaire of Cognitive Decline in the Elderly. HABAM score was recorded at admission. Out of 114 patients (mean age ± SD = 82 ± 7; 54% female), dementia alone was present in 24.6% (n = 28), delirium alone in 18.4% (n = 21) and DSD in 27.2% (n = 31). Patients with DSD had a mean HABAM score 7 points greater than those with dementia alone (19.8 ± 8.7 vs 12.5 ± 9.5; p < 0.001); 70% of participants with DSD were correctly identified using the HABAM at a cut off of 22 (sensitivity 61%, specificity 79%, AUC = 0.76). Individuals with delirium have worse motor function than those without delirium, even in the context of comorbid dementia. Measuring motor function using the HABAM in older people at admission may help to diagnose DSD.

Systematic review of prediction models for delirium in the older adult inpatient.

OBJECTIVE: To identify existing prognostic delirium prediction models and evaluate their validity and statistical methodology in the older adult (≥60 years) acute hospital population. DESIGN: Systematic review. DATA SOURCES AND METHODS: PubMed, CINAHL, PsychINFO, SocINFO, Cochrane, Web of Science and Embase were searched from 1 January 1990 to 31 December 2016. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses and CHARMS Statement guided protocol development. INCLUSION CRITERIA: age >60 years, inpatient, developed/validated a prognostic delirium prediction model. EXCLUSION CRITERIA: alcohol-related delirium, sample size ≤50. The primary performance measures were calibration and discrimination statistics. Two authors independently conducted search and extracted data. The synthesis of data was done by the first author. Disagreement was resolved by the mentoring author. RESULTS: The initial search resulted in 7,502 studies. Following full-text review of 192 studies, 33 were excluded based on age criteria (<60 years) and 27 met the defined criteria. Twenty-three delirium prediction models were identified, 14 were externally validated and 3 were internally validated. The following populations were represented: 11 medical, 3 medical/surgical and 13 surgical. The assessment of delirium was often non-systematic, resulting in varied incidence. Fourteen models were externally validated with an area under the receiver operating curve range from 0.52 to 0.94. Limitations in design, data collection methods and model metric reporting statistics were identified. CONCLUSIONS: Delirium prediction models for older adults show variable and typically inadequate predictive capabilities. Our review highlights the need for development of robust models to predict delirium in older inpatients. We provide recommendations for the development of such models.

Detecting delirium superimposed on dementia: diagnostic accuracy of a simple combined arousal and attention testing procedure.

BACKGROUND: Detecting delirium superimposed on dementia (DSD) can be challenging because assessment partly relies on cognitive tests that may be abnormal in both conditions. We hypothesized that a combined arousal and attention testing procedure would accurately detect DSD. METHODS: Patients aged ≥70 years were recruited from five hospitals across Europe. Delirium was diagnosed by physicians using DSM-5 criteria using information from nurses, carers, and medical records. Dementia was ascertained by the Informant Questionnaire on Cognitive Decline in the Elderly. Arousal was measured using the Observational Scale of Level of Arousal (OSLA), which assesses eye opening, eye contact, posture, movement, and communication. Attention was measured by participants signaling each time an "A" was heard when "S-A-V-E-A-H-A-A-R-T" was read out. RESULTS: The sample included 114 persons (mean age 82 years (SD 7); 54% women). Dementia alone was present in 25% (n = 28), delirium alone in 18% (n = 21), DSD in 27% (n = 31), and neither in 30% (n = 34). Arousal and attention was assessed in n = 109 (96%). Using OSLA, 83% participants were correctly identified as having delirium (sensitivity 85%, specificity 82%, AUROC 0.92). The attention task correctly classified 76% of participants with delirium (sensitivity 90%, specificity 64%, AUROC 0.80). Combining scores correctly classified 91% of participants with delirium (sensitivity 84%, specificity 92%, AUROC 0.94). Diagnostic accuracy remained high in the subgroup with dementia (93% correctly classified, sensitivity 94%, specificity 92%, AUROC 0.98). CONCLUSIONS: This combined arousal-attention assessment to detect DSD was brief yet had high diagnostic accuracy. Such an approach could have clinical utility for diagnosing DSD.

Protocol for the Delirium and Cognitive Impact in Dementia (DECIDE) study: A nested prospective longitudinal cohort study.

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.