The UK resuscitative endovascular balloon occlusion of the aorta in trauma patients with life-threatening torso haemorrhage: the (UK-REBOA) multicentre RCT.

Background: The most common cause of preventable death after injury is haemorrhage. Resuscitative endovascular balloon occlusion of the aorta is intended to provide earlier, temporary haemorrhage control, to facilitate transfer to an operating theatre or interventional radiology suite for definitive haemostasis. Objective: To compare standard care plus resuscitative endovascular balloon occlusion of the aorta versus standard care in patients with exsanguinating haemorrhage in the emergency department. Design: Pragmatic, multicentre, Bayesian, group-sequential, registry-enabled, open-label, parallel-group randomised controlled trial to determine the clinical and cost-effectiveness of standard care plus resuscitative endovascular balloon occlusion of the aorta, compared to standard care alone. Setting: United Kingdom Major Trauma Centres. Participants: Trauma patients aged 16 years or older with confirmed or suspected life-threatening torso haemorrhage deemed amenable to adjunctive treatment with resuscitative endovascular balloon occlusion of the aorta. Interventions: Participants were randomly assigned 1 : 1 to: standard care, as expected in a major trauma centre standard care plus resuscitative endovascular balloon occlusion of the aorta. Main outcome measures: Primary: Mortality at 90 days. Secondary: Mortality at 6 months, while in hospital, and within 24, 6 and 3 hours; need for haemorrhage control procedures, time to commencement of haemorrhage procedure, complications, length of stay (hospital and intensive care unit-free days), blood product use. Health economic: Expected United Kingdom National Health Service perspective costs, life-years and quality-adjusted life-years, modelled over a lifetime horizon. Data sources: Case report forms, Trauma Audit and Research Network registry, NHS Digital (Hospital Episode Statistics and Office of National Statistics data). Results: Ninety patients were enrolled: 46 were randomised to standard care plus resuscitative endovascular balloon occlusion of the aorta and 44 to standard care. Mortality at 90 days was higher in the standard care plus resuscitative endovascular balloon occlusion of the aorta group (54%) compared to the standard care group (42%). The odds ratio was 1.58 (95% credible interval 0.72 to 3.52). The posterior probability of an odds ratio > 1 (indicating increased odds of death with resuscitative endovascular balloon occlusion of the aorta) was 86.9%. The overall effect did not change when an enthusiastic prior was used or when the estimate was adjusted for baseline characteristics. For the secondary outcomes (3, 6 and 24 hours mortality), the posterior probability that standard care plus resuscitative endovascular balloon occlusion of the aorta was harmful was higher than for the primary outcome. Additional analyses to account for intercurrent events did not change the direction of the estimate for mortality at any time point. Death due to haemorrhage was more common in the standard care plus resuscitative endovascular balloon occlusion of the aorta group than in the standard care group. There were no serious adverse device effects. Resuscitative endovascular balloon occlusion of the aorta is less costly (probability 99%), due to the competing mortality risk but also substantially less effective in terms of lifetime quality-adjusted life-years (probability 91%). Limitations: The size of the study reflects the relative infrequency of exsanguinating traumatic haemorrhage in the United Kingdom. There were some baseline imbalances between groups, but adjusted analyses had little effect on the estimates. Conclusions: This is the first randomised trial of the addition of resuscitative endovascular balloon occlusion of the aorta to standard care in the management of exsanguinating haemorrhage. All the analyses suggest that a strategy of standard care plus resuscitative endovascular balloon occlusion of the aorta is potentially harmful. Future work: The role (if any) of resuscitative endovascular balloon occlusion of the aorta in the pre-hospital setting remains unclear. Further research to clarify its potential (or not) may be required. Trial registration: This trial is registered as ISRCTN16184981. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/199/09) and is published in full in Health Technology Assessment; Vol. 28, No. 54. See the NIHR Funding and Awards website for further award information.

Trauma (physical injury) is a major cause of death and disability. The most common cause of preventable death after injury is uncontrolled bleeding. Resuscitative endovascular balloon occlusion of the aorta is a technique whereby a small balloon is inflated in the aorta (main blood vessel) which aims to limit blood loss until an operation can be done to stop the bleeding. In this study, which is the first randomised trial in the world of this technique, we investigated whether adding resuscitative endovascular balloon occlusion of the aorta to the standard care received in a major trauma centre reduced the risk of death in trauma patients who had life-threatening uncontrolled bleeding. The study took place in 16 major trauma centres in the United Kingdom. Ninety adult trauma patients with confirmed or suspected uncontrolled bleeding took part and were randomly divided into two groups: (1) those who received standard care and (2) those who received standard care plus resuscitative endovascular balloon occlusion of the aorta. We followed participants for 6 months using routinely collected data from the National Health Service and from the Trauma Audit Research Network registry. We also contacted surviving patients at 6 months to ask about their quality of life. In the standard care group, 42% of participants died within 90 days of their injury compared to 54% of participants in the standard care plus resuscitative endovascular balloon occlusion of the aorta group. Risk of death was also higher in the standard care plus resuscitative endovascular balloon occlusion of the aorta group at all other time points (3, 6 and 24 hours, in hospital and at 6 months). Overall, the study showed that the use of resuscitative endovascular balloon occlusion of the aorta in hospital increased the risk of death.

Experiences of healthcare staff caring for hospitalised people with delirium: a qualitative systematic review.

BACKGROUND: Inpatient delirium is common and associated with poor outcomes. Although most organisations have evidence-based guidelines to improve delirium prevention and management, delirium rates and outcomes have remained relatively unchanged over time. A lack of understanding of healthcare providers' experience of caring for people with delirium and its integration into existing guidance may explain some of the slow progress in improving delirium care. OBJECTIVE: To review and synthesise existing qualitative evidence on healthcare providers' experience of caring for inpatients with delirium within and across disciplines. METHODS: We systematically searched OVID Medline, CINAHL, Embase, Emcare, PsychINFO, AMED and Web of Science databases for articles published between January 1990 and November 2022. Article inclusion and study quality were assessed by two independent reviewers. Both thematic synthesis and content analysis were then conducted to synthesise findings from included studies. RESULTS: Within the 25 included studies, the experience of nurses was the most commonly studied perspective, followed by medical and allied health. Nursing, medical and allied health staff all reported that their experience of caring for people with delirium was challenging, highlighting difficulties in delirium recognition and that they felt unsupported at organisational and local levels. Attitudes towards older people and the importance of delirium influenced identification and prioritisation. CONCLUSIONS: Healthcare providers often find caring for hospitalised patients with delirium challenging and complex. Although good communication within multidisciplinary teams was deemed helpful, more work is required to understand how to achieve this, recognising the unique perspectives of individual disciplines.

HbA1c variability associated with dementia risk in people with type 2 diabetes.

INTRODUCTION: Although poor glycemic control is associated with dementia, it is unknown if variability in glycemic control, even in those with optimal glycosylated hemoglobin A1c (HbA1c) levels, increases dementia risk. METHODS: Among 171,964 people with type 2 diabetes, we evaluated the hazard of dementia association with long-term HbA1c variability using five operationalizations, including standard deviation (SD), adjusting for demographics and comorbidities. RESULTS: The mean baseline age was 61 years (48% women). Greater HbA1c SD was associated with greater dementia hazard (adjusted hazard ratio = 1.15 [95% confidence interval: 1.12, 1.17]). In stratified analyses, higher HbA1c SD quintiles were associated with greater dementia hazard among those with a mean HbA1c < 6% (P = 0.0004) or 6% to 8% (P < 0.0001) but not among those with mean HbA1c ≥ 8% (P = 0.42). DISCUSSION: Greater HbA1c variability is associated with greater dementia risk, even among those with HbA1c concentrations at ideal clinical targets. These findings add to the importance and clinical impact of recommendations to minimize glycemic variability. HIGHLIGHTS: We observed a cohort of 171,964 people with type 2 diabetes (mean age 61 years). This cohort was based in Northern California between 1996 and 2018. We examined the association between glycosylated hemoglobin A1c (HbA1c) variability and dementia risk. Greater HbA1c variability was associated with greater dementia hazard. This was most evident among those with normal-low mean HbA1c concentrations.

The association of regional cerebral blood flow and glucose metabolism in normative ageing and insulin resistance.

Rising rates of insulin resistance and an ageing population are set to exact an increasing toll on individuals and society. Here we examine the contribution of age and insulin resistance to the association of cerebral blood flow and glucose metabolism; both critical process in the supply of energy for the brain. Thirty-four younger (20-42 years) and 41 older (66-86 years) healthy adults underwent a simultaneous resting state MR/PET scan, including arterial spin labelling. Rates of cerebral blood flow and glucose metabolism were derived using a functional atlas of 100 brain regions. Older adults had lower cerebral blood flow than younger adults in 95 regions, reducing to 36 regions after controlling for cortical atrophy and blood pressure. Lower cerebral blood flow was also associated with worse working memory and slower reaction time in tasks requiring cognitive flexibility and response inhibition. Younger and older insulin sensitive adults showed small, negative correlations between relatively high rates of regional cerebral blood flow and glucose metabolism. This pattern was inverted in insulin resistant older adults, who showed hypoperfusion and hypometabolism across the cortex, and a positive correlation. In insulin resistant younger adults, the association showed inversion to positive correlations, although not to the extent seen in older adults. Our findings suggest that the normal course of ageing and insulin resistance alter the rates of and associations between cerebral blood flow and glucose metabolism. They underscore the criticality of insulin sensitivity to brain health across the adult lifespan.

Interactions between age, sex and visceral adipose tissue on brain ageing.

AIM: To examine the associations between visceral adipose tissue (VAT) and brain structural measures at midlife and explore how these associations may be affected by age, sex and cardiometabolic factors. METHODS: We used abdominal and brain magnetic resonance imaging data from a population-based cohort of people at midlife in the UK Biobank. Regression modelling was applied to study associations of VAT volume with total brain volume (TBV), grey matter volume (GMV), white matter volume, white matter hyperintensity volume (WMHV) and total hippocampal volume (THV), and whether these associations were altered by age, sex or cardiometabolic factors. RESULTS: Complete data were available for 17 377 participants (mean age 63 years, standard deviation = 12, 53% female). Greater VAT was associated with lower TBV, GMV and THV (P < .001). We found an interaction between VAT and sex on TBV (P < .001), such that the negative association of VAT with TBV was greater in men (ß = -2.89, 95% confidence interval [CI] -2.32 to -10.15) than in women (ß = -1.32, 95% CI -0.49 to -3.14), with similar findings for GMV. We also found an interaction between VAT and age (but not sex) on WMHV (P < .001). The addition of other cardiometabolic factors or measures of physical activity resulted in little change to the models. CONCLUSIONS: VAT volume is associated with poorer brain health in midlife and this relationship is greatest in men and those at younger ages.

Hospital and out-of-hospital services provided by public geriatric medicine departments in Australia and New Zealand.

OBJECTIVE: To describe the types of hospital and out-of-hospital services provided by public geriatric medicine departments in Australia and New Zealand, and to explore head of department (HOD) views on issues in current and future service provision. METHODS: An electronic survey was sent to HODs of public geriatric medicine departments. RESULTS: Seventy-six (89%) of 85 identified HODs completed the survey. Seventy-one (93%) departments admit inpatients and 51 (67%) admit acute inpatients, with variable admission criteria. Sixty-four (84%) have hospitals with an inpatient general medicine service, and 58 (91%) of these admit older patients with acute geriatric issues. Sixty (79%) departments provide inpatient rehabilitation. Forty (53%) have beds for behavioural symptoms of dementia and/or delirium. Seventy (92%) provide a proactive orthogeriatric service. In terms of out-of-hospital services, 74 (97%) departments have outpatient clinics, 59 (78%) have telehealth and 68 (89%) perform home visits. Forty-five (59%) provide an inreach/outreach service to nursing homes. The most frequent gaps in service provision identified by HODs were acute geriatrics, surgical liaison, a designated dementia/delirium behavioural management unit, geriatricians in Emergency, outreach/inreach to residential care and shared care with some medical specialities. Increasing staff numbers and government policy change were the most frequently identified ways to address these gaps. CONCLUSIONS: Geriatric medicine service provision is variable across Australia and New Zealand, with key gaps identified. These findings will inform future directions in implementation of geriatric medicine models of care and discussions with various levels of government about the ongoing development of geriatric medicine services.

The implementation of a perioperative medicine for older people undergoing surgery service: a qualitative case study.

BACKGROUND: The international scale and spread of evidence-based perioperative medicine for older people undergoing surgery (POPS) services has not yet been fully realised. Implementation science provides a structured approach to understanding factors that act as barriers and facilitators to the implementation of POPS services. In this study, we aimed to identify factors that influence the implementation of POPS services in the UK. METHODS: A qualitative case study at three UK health services was undertaken. The health services differed across contextual factors (population, workforce, size) and stages of POPS service implementation maturity. Semi-structured interviews with purposively sampled clinicians (perioperative medical, nursing, allied health, and pharmacy) and managers (n = 56) were conducted. Data were inductively coded, then thematically analysed using the Consolidated Framework for Implementation Research (CFIR). RESULTS: Fourteen factors across all five CFIR domains were relevant to the implementation of POPS services. Key shared facilitators included stakeholders understanding the rationale of the POPS service, with support from their networks, POPS champions, and POPS clinical leads. We found substantial variation and flexibility in the way that health services responded to these shared facilitators and this was relevant to the implementation of POPS services. CONCLUSIONS: Health services planning to implement a POPS service should use health service-specific strategies to respond flexibly to local factors that are acting as barriers or facilitators to implementation. To support implementation of a POPS service, we recommend health services prioritise understanding local networks, identifying POPS champions, and ensuring that stakeholders understand the rationale for the POPS service. Our study also provides a structure for future research to understand the factors associated with 'unsuccessful' implementation of a POPS service, which can inform ongoing efforts to implement evidence-based perioperative models of care for older people.

Type 2 Diabetes and Biomarkers of Brain Structure, Perfusion, Metabolism, and Function in Late Mid-Life: A Multimodal Discordant Twin Study.

BACKGROUND: Type 2 diabetes (T2D) is associated with an increased risk of dementia and early features may become evident even in mid-life. Characterizing these early features comprehensively requires multiple measurement modalities and careful selection of participants with and without T2D. OBJECTIVE: We conducted a cross-sectional multimodal imaging study of T2D-discordant twins in late mid-life to provide insights into underlying mechanisms. METHODS: Measurements included computerized cognitive battery, brain MRI (including arterial spin labelling, diffusion tensor, resting state functional), fluorodeoxyglucose (FDG)-PET, and retinal optical coherence tomography. RESULTS: There were 23 pairs, mean age 63.7 (±6.1) years. In global analyses, T2D was associated with poorer attention (ß= -0.45, p <0.001) and with reduced FDG uptake (ß= -5.04, p = 0.02), but not with cortical thickness (p = 0.71), total brain volume (p = 0.51), fractional anisotropy (p = 0.15), mean diffusivity (p = 0.34), or resting state activity (p = 0.4). Higher FDG uptake was associated with better attention (ß= 3.19, p = 0.01) but not with other cognitive domains. In regional analyses, T2D was associated with lower accumbens volume (ß= -44, p = 0.0004) which was in turn associated with poorer attention. CONCLUSION: T2D-related brain dysfunction in mid-life manifests as attentional loss accompanied by evidence of subtle neurodegeneration and global reduction in cerebral metabolism, in the absence of overt cerebrovascular disease.

Emergency Department Resuscitative Endovascular Balloon Occlusion of the Aorta in Trauma Patients With Exsanguinating Hemorrhage: The UK-REBOA Randomized Clinical Trial.

Importance: Bleeding is the most common cause of preventable death after trauma. Objective: To determine the effectiveness of resuscitative endovascular balloon occlusion of the aorta (REBOA) when used in the emergency department along with standard care vs standard care alone on mortality in trauma patients with exsanguinating hemorrhage. Design, Setting, and Participants: Pragmatic, bayesian, randomized clinical trial conducted at 16 major trauma centers in the UK. Patients aged 16 years or older with exsanguinating hemorrhage were enrolled between October 2017 and March 2022 and followed up for 90 days. Intervention: Patients were randomly assigned (1:1 allocation) to a strategy that included REBOA and standard care (n = 46) or standard care alone (n = 44). Main Outcomes and Measures: The primary outcome was all-cause mortality at 90 days. Ten secondary outcomes included mortality at 6 months, while in the hospital, and within 24 hours, 6 hours, or 3 hours; the need for definitive hemorrhage control procedures; time to commencement of definitive hemorrhage control procedures; complications; length of stay; blood product use; and cause of death. Results: Of the 90 patients (median age, 41 years [IQR, 31-59 years]; 62 [69%] were male; and the median Injury Severity Score was 41 [IQR, 29-50]) randomized, 89 were included in the primary outcome analysis because 1 patient in the standard care alone group declined to provide consent for continued participation and data collection 4 days after enrollment. At 90 days, 25 of 46 patients (54%) had experienced all-cause mortality in the REBOA and standard care group vs 18 of 43 patients (42%) in the standard care alone group (odds ratio [OR], 1.58 [95% credible interval, 0.72-3.52]; posterior probability of an OR >1 [indicating increased odds of death with REBOA], 86.9%). Among the 10 secondary outcomes, the ORs for mortality and the posterior probabilities of an OR greater than 1 for 6-month, in-hospital, and 24-, 6-, or 3-hour mortality were all increased in the REBOA and standard care group, and the ORs were increased with earlier mortality end points. There were more deaths due to bleeding in the REBOA and standard care group (8 of 25 patients [32%]) than in standard care alone group (3 of 18 patients [17%]), and most occurred within 24 hours. Conclusions and Relevance: In trauma patients with exsanguinating hemorrhage, a strategy of REBOA and standard care in the emergency department does not reduce, and may increase, mortality compared with standard care alone. Trial Registration: isrctn.org Identifier: ISRCTN16184981.

Quantitative trait and transcriptome analysis of genetic complexity underpinning cardiac interatrial septation in mice using an advanced intercross line.

Unlike single-gene mutations leading to Mendelian conditions, common human diseases are likely to be emergent phenomena arising from multilayer, multiscale, and highly interconnected interactions. Atrial and ventricular septal defects are the most common forms of cardiac congenital anomalies in humans. Atrial septal defects (ASD) show an open communication between the left and right atria postnatally, potentially resulting in serious hemodynamic consequences if untreated. A milder form of atrial septal defect, patent foramen ovale (PFO), exists in about one-quarter of the human population, strongly associated with ischaemic stroke and migraine. The anatomic liabilities and genetic and molecular basis of atrial septal defects remain unclear. Here, we advance our previous analysis of atrial septal variation through quantitative trait locus (QTL) mapping of an advanced intercross line (AIL) established between the inbred QSi5 and 129T2/SvEms mouse strains, that show extremes of septal phenotypes. Analysis resolved 37 unique septal QTL with high overlap between QTL for distinct septal traits and PFO as a binary trait. Whole genome sequencing of parental strains and filtering identified predicted functional variants, including in known human congenital heart disease genes. Transcriptome analysis of developing septa revealed downregulation of networks involving ribosome, nucleosome, mitochondrial, and extracellular matrix biosynthesis in the 129T2/SvEms strain, potentially reflecting an essential role for growth and cellular maturation in septal development. Analysis of variant architecture across different gene features, including enhancers and promoters, provided evidence for the involvement of non-coding as well as protein-coding variants. Our study provides the first high-resolution picture of genetic complexity and network liability underlying common congenital heart disease, with relevance to human ASD and PFO.

Glycemic Control Over Multiple Decades and Dementia Risk in People With Type 2 Diabetes.

Importance: The levels of glycemic control associated with the lowest risk of dementia in people with type 2 diabetes are unknown. This knowledge is critical to inform patient-centered glycemic target setting. Objective: To examine the associations between cumulative exposure to various ranges of glycated hemoglobin (HbA1c) concentrations with dementia risk across sex and racial and ethnic groups and the association of current therapeutic glycemic targets with dementia risk. Design, Setting, and Participants: This cohort study included members of the Kaiser Permanente Northern California integrated health care system with type 2 diabetes who were aged 50 years or older during the study period from January 1, 1996, to September 30, 2015. Individuals with fewer than 2 HbA1c measurements during the study period, prevalent dementia at baseline, or less than 3 years of follow-up were excluded. Data were analyzed from February 2020 to January 2023. Exposures: Time-updated cumulative exposure to HbA1c thresholds. At each HbA1c measurement, participants were categorized based on the percentage of their HbA1c measurements that fell into the following categories: less than 6%, 6% to less than 7%, 7% to less than 8%, 8% to less than 9%, 9% to less than 10%, and 10% or more of total hemoglobin (to convert percentage of total hemoglobin to proportion of total hemoglobin, multiply by 0.01). Main Outcomes and Measures: Dementia diagnosis was identified using International Classification of Diseases, Ninth Revision codes from inpatient and outpatient encounters. Cox proportional hazards regression models estimated the association of time-varying cumulative glycemic exposure with dementia, adjusting for age, race and ethnicity, baseline health conditions, and number of HbA1c measurements. Results: A total of 253 211 participants were included. The mean (SD) age of participants was 61.5 (9.4) years, and 53.1% were men. The mean (SD) duration of follow-up was 5.9 (4.5) years. Participants with more than 50% of HbA1c measurements at 9% to less than 10% or 10% or more had greater risk of dementia compared with those who had 50% or less of measurements in those categories (HbA1c 9% to <10%: adjusted hazard ratio [aHR], 1.31 [95% CI, 1.15-1.51]; HbA1c≥10%: aHR, 1.74 [95% CI, 1.62-1.86]). By contrast, participants with more than 50% of HbA1c concentrations less than 6%, 6% to less than 7%, or 7% to less than 8% had lower risk of dementia (HbA1c<6%: aHR, 0.92 [95% CI, 0.88-0.97]; HbA1c 6% to <7%: aHR, 0.79 [95% CI, 0.77-0.81]; HbA1c 7% to <8%: aHR, 0.93 [95% CI, 0.89-0.97]). Conclusions and Relevance: In this study dementia risk was greatest among adults with cumulative HbA1c concentrations of 9% or more. These results support currently recommended relaxed glycemic targets for older people with type 2 diabetes.

Potentially inappropriate medication use is associated with increased risk of incident disability in healthy older adults.

BACKGROUND: Efforts to minimize medication risks among older adults include avoidance of potentially inappropriate medications (PIMs). However, most PIMs research has focused on older people in aged or inpatient care, creating an evidence gap for community-dwelling older adults. To address this gap, we investigated the impact of PIMs use in the ASPirin in Reducing Events in the Elderly (ASPREE) clinical trial cohort. METHODS: Analysis included 19,114 community-dwelling ASPREE participants aged 70+ years (65+ if US minorities) without major cardiovascular disease, cognitive impairment, or significant physical disability. PIMs were defined according to a modified 2019 AGS Beers Criteria. Cox proportional-hazards regression models were used to estimate the association between baseline PIMs exposure and disability-free survival, death, incident dementia, disability, and hospitalization, with adjustment for sex, age, country, years of education, frailty, average gait speed, and comorbidities. RESULTS: At baseline, 7396 (39% of the total) participants were prescribed at least one PIM. Compared with those unexposed, participants on a PIM at baseline were at an increased risk of persistent physical disability (adjusted hazard ratio [HR] 1.47, 95% confidence interval [CI] 1.21, 1.80) and hospitalization (adjusted HR 1.26, 95% CI 1.20, 1.32), but had similar rates of disability-free survival (adjusted HR 1.02; 95% CI 0.93, 1.13) and death (adjusted HR 0.92, 95% CI 0.81, 1.05). These effects did not vary by polypharmacy status in interaction analyses. PIMs exposure was associated with higher risk of disability followed by hospitalization (adjusted HR 1.92, 95% CI 1.25, 2.96) as well as vice versa (adjusted HR 1.54, 95% CI 1.15, 2.05). PPIs, anti-psychotics and benzodiazepines, were associated with increased risk of disability. CONCLUSIONS: PIMs exposure is associated with subsequent increased risk of both incident disability and hospitalization. Increased risk of disability prior to hospitalization suggests that PIMs use may start the disability cascade in healthy older adults. Our findings emphasize the importance of caution when prescribing PIMs to older adults in otherwise good health.

Lower brain glucose metabolism in normal ageing is predominantly frontal and temporal: A systematic review and pooled effect size and activation likelihood estimates meta-analyses.

This review provides a qualitative and quantitative analysis of cerebral glucose metabolism in ageing. We undertook a systematic literature review followed by pooled effect size and activation likelihood estimates (ALE) meta-analyses. Studies were retrieved from PubMed following the PRISMA guidelines. After reviewing 635 records, 21 studies with 22 independent samples (n = 911 participants) were included in the pooled effect size analyses. Eight studies with eleven separate samples (n = 713 participants) were included in the ALE analyses. Pooled effect sizes showed significantly lower cerebral metabolic rates of glucose for older versus younger adults for the whole brain, as well as for the frontal, temporal, parietal, and occipital lobes. Among the sub-cortical structures, the caudate showed a lower metabolic rate among older adults. In sub-group analyses controlling for changes in brain volume or partial volume effects, the lower glucose metabolism among older adults in the frontal lobe remained significant, whereas confidence intervals crossed zero for the other lobes and structures. The ALE identified nine clusters of lower glucose metabolism among older adults, ranging from 200 to 2640 mm3 . The two largest clusters were in the left and right inferior frontal and superior temporal gyri and the insula. Clusters were also found in the inferior temporal junction, the anterior cingulate and caudate. Taken together, the results are consistent with research showing less efficient glucose metabolism in the ageing brain. The findings are discussed in the context of theories of cognitive ageing and are compared to those found in neurodegenerative disease.

The older adult brain is less modular, more integrated, and less efficient at rest: A systematic review of large-scale resting-state functional brain networks in aging.

The literature on large-scale resting-state functional brain networks across the adult lifespan was systematically reviewed. Studies published between 1986 and July 2021 were retrieved from PubMed. After reviewing 2938 records, 144 studies were included. Results on 11 network measures were summarized and assessed for certainty of the evidence using a modified GRADE method. The evidence provides high certainty that older adults display reduced within-network and increased between-network functional connectivity. Older adults also show lower segregation, modularity, efficiency and hub function, and decreased lateralization and a posterior to anterior shift at rest. Higher-order functional networks reliably showed age differences, whereas primary sensory and motor networks showed more variable results. The inflection point for network changes is often the third or fourth decade of life. Age effects were found with moderate certainty for within- and between-network altered patterns and speed of dynamic connectivity. Research on within-subject bold variability and connectivity using glucose uptake provides low certainty of age differences but warrants further study. Taken together, these age-related changes may contribute to the cognitive decline often seen in older adults.

Cognitive trajectories during the menopausal transition.

Aims: Female sex is associated with an increased prevalence of dementia. Menopause may have a role to play in explaining sex differences in cognition, and possibly the risk of future dementia. We aimed to determine if the rate of cognitive decline differed between stages of the menopausal transition. Materials and methods: Women with data on menopause and longitudinal cognitive function from the UK Biobank study were stratified into three groups: premenopausal, perimenopausal and postmenopausal. We studied associations of these menopause groups with rate of change in reaction time, verbal-numeric reasoning, prospective memory, visual memory and attention/working memory, adjusted for age, education, ethnicity and APOEε4 genotype. We also explored the effect of menopausal hormonal therapy (MHT) use and cross-sectional brain magnetic resonance imaging (MRI) volumes on these models. Results: We included 15,486 women (baseline mean age 52 years) over a mean duration of 8 years. An interaction between menopausal group status and time was found for reaction time (p < 0.01). Compared with premenopausal women, the rate of increase (worsening) in reaction time was least in postmenopausal women (ß = -1.07, p for interaction = 0.02). In general, compared with premenopausal women, perimenopausal and postmenopausal women had overall poorer performance in fluid intelligence and memory over the study duration, with no difference in rates of change. The models were unaffected by MHT use and brain volume measures. Conclusions: Perimenopause and post-menopause are associated with cognitive changes. Psychomotor speed appears to be most sensitive to the menopause transition, whereas other cognitive functions may be less susceptible. More sensitive structural or functional brain imaging may be required to understand the underlying neural basis for these findings.

New NHS Prehospital Major Incident Triage Tool: from MIMMS to MITT.

Triage is a key principle in the effective management of major incidents and is the process by which patients are prioritised on the basis of their clinical acuity. However, work published over the last decade has demonstrated that existing methods of triage perform poorly when trying to identify patients in need of life-saving interventions. As a result, a review of major incident triage was initiated by NHS England with the remit to determine the optimum way in which to triage patients of all ages in a major incident for the UK. This article describes the output from this review, the changes being undertaken to UK major incident triage and the introduction of the new NHS Major Incident Triage Tool from the Spring of 2023.

Associations of Sex, Age, and Cardiometabolic Risk Profiles With Brain Structure and Cognition: A UK Biobank Latent Class Analysis.

BACKGROUND AND OBJECTIVES: It is unknown whether there are sex-related profiles of cardiometabolic health that contribute differently to age-related changes in brain health during midlife. We studied how latent classes of middle-aged individuals clustering by age, sex, menopause, and cardiometabolic health were associated with brain structure and cognitive performance. METHODS: Health, brain, and abdominal MRI data from the UK Biobank cohort (men and women aged >40 years in the United Kingdom) were used. We applied latent class analysis to identify groups of individuals based on age, sex, menopausal status, and cardiometabolic health. We examined associations of class membership with brain volumes (total brain volume [TBV], gray matter volume [GMV], white matter volume [WMV], hippocampal volume, and white matter hyperintensity volume) and cognitive performance. RESULTS: Data were available for 36,420 individuals (mean age 64.9 years, 48.5% women). Eight latent classes differing in age, sex, and cardiometabolic risk were identified. Class 1 (reference class) included individuals with the lowest probability of older age and cardiometabolic risk, and the healthiest levels of brain volumes and cognition. In those aged >60 years, but not in those aged 50-60 years, the negative associations of age with TBV, GMV, and WMV were greater in the class comprising healthier older women than classes comprising older men of varying cardiometabolic and vascular health. There were no age-class interactions for cognitive test performance. DISCUSSION: Latent class analysis detected groups of middle-aged individuals clustering by cardiometabolic health. The relationship of age with brain volumes varies by sex, menopausal status, and cardiometabolic health profile.

Longitudinal associations of childhood fitness and obesity profiles with midlife cognitive function: an Australian cohort study.

OBJECTIVES: Clusters of low fitness and high obesity in childhood are associated with poorer health outcomes in later life, however their relationship with cognition is unknown. Identifying such profiles may inform strategies to reduce risk of cognitive decline. This study examined whether specific profiles of childhood fitness and obesity were associated with midlife cognition. DESIGN: Prospective study. METHODS: In 1985, participants aged 7-15 years from the Australian Childhood Determinants of Adult Health study were assessed for fitness (cardiorespiratory, muscular power, muscular endurance) and anthropometry (waist-to-hip ratio). Participants were followed up between 2017 and 2019 (aged 39-50). Composites of psychomotor speed-attention, learning-working memory and global cognition were assessed using CogState computerised battery. Latent profile analysis was used to derive mutually exclusive profiles based on fitness and anthropometry. Linear regression analyses examined associations between childhood profile membership and midlife cognition adjusting for age, sex and education level. RESULTS: 1244 participants were included [age: 44.4 ±â€¯2.6 (mean ±â€¯SD) years, 53% female]. Compared to those with the highest levels of fitness and lowest waist-to-hip ratio, three different profiles characterised by combinations of poorer cardiorespiratory fitness, muscular endurance and power were associated with lower midlife psychomotor-attention [up to -1.09 (-1.92, -0.26) SD], and lower global cognition [up to -0.71 (-1.41, -0.01) SD]. No associations were detected with learning-working memory. CONCLUSIONS: Strategies that improve low fitness and decrease obesity levels in childhood could contribute to improvements in cognitive performance in midlife.

Neuroimaging and cognitive correlates of retinal Optical Coherence Tomography (OCT) measures at late middle age in a twin sample.

Sharing in embryology and function between the eye and brain has led to interest in whether assessments of the eye reflect brain changes seen in neurodegeneration. We aimed to examine the associations between measures of retinal layer thickness using optical coherence tomography (OCT) and multimodal measures of brain structure and function. Using a convenient sample of twins discordant for type 2 diabetes, we performed cognitive testing, structural brain MRI (tissue volumetry), diffusion tensor imaging (white matter microstructure), and arterial spin labelling (cerebral blood flow). OCT images were recorded and retinal thickness maps generated. We used mixed level modelling to examine the relationship between retinal layer thicknesses and brain measures. We enrolled 35 people (18 pairs, mean age 63.8 years, 63% female). Ganglion cell layer thickness was positively associated with memory, speed, gray matter volume, and altered mean diffusivity. Ganglion cell layer thickness was strongly positively associated with regional cerebral blood flow. We found only a limited number of associations between other retinal layer thickness and measures of brain structure or function. Ganglion cell layer thickness showed consistent associations with a range of brain measures suggesting it may have utility as a marker for future dementia risk.