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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

IntroductionThe incidence of both type 1 diabetes (T1D) and type 2 diabetes (T2D) is increasing. Life expectancy is improving in T1D, resulting in a growing population of elderly adults with diabetes. While it is well established that older adults with T2D are at increased risk of cognitive impairment, little is known regarding cognitive aging in T1D and how their cognitive profiles may differ from T2D.Research design and methodsWe compared baseline cognitive function and low cognitive function by diabetes status (n=734 T1D, n=232 T2D, n=247 without diabetes) among individuals from the Study of Longevity in Diabetes (mean age=68). We used factor analysis to group cognition into five domains and a composite measure of total cognition. Using linear and logistic regression models, we examined the associations between diabetes type and cognitive function, adjusting for demographics, comorbidities, depression, and sleep quality.ResultsT1D was associated with lower scores on total cognition, language, executive function/psychomotor processing speed, and verbal episodic memory, and greater odds of low executive function/psychomotor processing speed (OR=2.99, 95% CI 1.66 to 5.37) and verbal episodic memory (OR=1.92, 95% CI 1.07 to 3.46), compared with those without diabetes. T2D was associated with lower scores on visual episodic memory. Compared with T2D, T1D was associated with lower scores on verbal episodic memory and executive function/psychomotor processing speed and greater odds of low executive function/psychomotor processing speed (OR=1.74, 95% CI 1.03 to 2.92).ConclusionsOlder adults with T1D had significantly poorer cognition compared with those with T2D and those without diabetes even after accounting for a range of comorbidities. Future studies should delineate how to reduce risk in this vulnerable population who are newly surviving to old age.

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 (β = −2.89, 95% confidence interval [CI] −2.32 to −10.15) than in women (β = −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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Key Points: Question: Does the addition of resuscitative endovascular balloon occlusion of the aorta (REBOA) to standard care reduce mortality in trauma patients with exsanguinating hemorrhage? Findings: In this bayesian randomized clinical trial that included 89 patients at 90 days, all-cause mortality was 54% in the REBOA and standard care group vs 42% in the standard care alone group (odds ratio, 1.58; posterior probability of increased odds of death with REBOA, 86.9%). Meaning: 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. 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 This randomized clinical trial compares the effectiveness of resuscitative endovascular balloon occlusion of the aorta and standard care in the emergency department vs standard care alone on mortality in trauma patients with exsanguinating hemorrhage. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. Although the literature on large‐scale, resting state functional networks in aging has been reviewed previously, we offer the first systematic qualitative and quantitative synthesis of the evidence. The novel synthesis stems from the adoption of PRISMA method and the breadth of network measures reviewed. The review offers a contemporary summary of the strength of the evidence, theoretical implications, and recommendations for further research. [ABSTRACT FROM AUTHOR]

Objectives: There is a lack of guidance on how to manage the multiple post‐discharge issues of older people following minimal trauma hip fracture. We developed a geriatrician‐staffed outpatient service for people aged ≥65 years admitted with a hip fracture who were not discharged to a nursing home. We aimed to evaluate the potential benefits of the addition of a dedicated hip fracture follow‐up clinic by measuring the actions performed by such a clinic. Methods: We evaluated the potential benefit of the clinic through a retrospective review of the medical records of all those referred to the clinic over a 2‐year period. Results: A total of 80 people were provided a clinic appointment, with 43 (54%) attending. The median age of clinic attendees was 81 years. A total of 40/43 (93%) of attendees received inpatient rehabilitation in a sub‐acute facility before discharge. At the dedicated outpatient clinic, multiple issues were identified and managed including further fall reduction strategies (n = 12), commencement of anti‐resorptive medications (n = 11) and medication deprescribing (n = 11). Conclusions: We found that the introduction of a dedicated hip fracture outpatient clinic identified and managed a broad range of issues. It is unclear if these needs would have been met by previously existing services. Further work is required to clarify whether managing these issues translates into improved patient outcomes and whether a dedicated clinic is a cost‐effective practice of achieving this. [ABSTRACT FROM AUTHOR]

Background: Haemorrhage is the most common cause of preventable death after injury. REBOA is a novel technique whereby a percutaneously inserted balloon is deployed in the aorta, providing a relatively quick means of temporarily controlling haemorrhage and augmenting cerebral and coronary perfusion, until definitive control of haemorrhage can be attained. The aim of the UK-REBOA trial is to establish the clinical and cost-effectiveness of a policy of standard major trauma centre treatment plus REBOA, as compared with standard major trauma centre treatment alone, for the management of uncontrolled torso haemorrhage caused by injury.Methods: Pragmatic, Bayesian, group-sequential, randomised controlled trial, performed in 16 major trauma centres in England. We aim to randomise 120 injured patients with suspected exsanguinating haemorrhage to either standard major trauma centre care plus REBOA or standard major trauma centre care alone. The primary clinical outcome is 90-day mortality. Secondary clinical outcomes include 3-h, 6-h, and 24-h mortality; in-hospital mortality; 6-month mortality; length of stay (in hospital and intensive care unit); 24-h blood product use; need for haemorrhage control procedure (operation or angioembolisation); and time to commencement of haemorrhage control procedure (REBOA, operation, or angioembolisation). The primary economic outcome is lifetime incremental cost per QALY gained, from a health and personal social services perspective.Discussion: This study, which is the first to randomly allocate patients to treatment with REBOA or standard care, will contribute high-level evidence on the clinical and cost-effectiveness of REBOA in the management of trauma patients with exsanguinating haemorrhage and will provide important data on the feasibility of implementation of REBOA into mainstream clinical practice.Trial Registration: ISRCTN16184981. [ABSTRACT FROM AUTHOR]

The prevalence of type 2 diabetes (T2D) and cognitive dysfunction increases with age. As society ages, clinicians will be increasingly tasked with managing older people who have both T2D and cognitive dysfunction. T2D is associated with an increased risk of cognitive dysfunction and hence there is increasing interest in whether T2D is a causal factor in the pathogenesis of cognitive decline and dementia. Recent advances in the use of sensitive measures of in vivo brain dysfunction in life-course studies can help understand potential mechanistic pathways and also help guide recommendations for clinical practice. In this article we will describe new horizons in the understanding of cognitive dysfunction associated with T2D. Coming from a clinical perspective, we discuss potential mechanisms and pathways linking the 2 conditions and the contribution of multimodal neuroimaging and study designs to advancing understanding in the field. We also highlight the important issues on the horizon that will need addressing in clinical identification, management, and risk reduction for people with coexistent T2D and cognitive dysfunction. [ABSTRACT FROM AUTHOR]