Building a framework to decolonize global emergency medicine.

Background: Global emergency medicine (GEM) is situated at the intersection of global health and emergency medicine (EM), which is built upon a history of colonial systems and institutions that continue to reinforce inequities between high-income countries (HICs) and low- and middle-income countries (LMICs) today. These power imbalances yield disparities in GEM practice, research, and education. Approach: The Global Emergency Medicine Academy (GEMA) of the Society for Academic Emergency Medicine formed the Decolonizing GEM Working Group in 2020, which now includes over 100 worldwide members. The mission is to address colonial legacies in GEM and catalyze sustainable changes and recommendations toward decolonization at individual and institutional levels. To develop recommendations to decolonize GEM, the group conducted a nonsystematic review of existing literature on decolonizing global health, followed by in-depth discussions between academics from LMICs and HICs to explore implications and challenges specific to GEM. We then synthesized actionable solutions to provide recommendations on decolonizing GEM. Results: Despite the rapidly expanding body of literature on decolonizing global health, there is little guidance specific to the relatively new field of GEM. By applying decolonizing principles to GEM, we suggest key priorities for improving equity in academic GEM: (1) reframing partnerships to place LMIC academics in positions of expertise and power, (2) redirecting research funding toward LMIC-driven projects and investigators, (3) creating more equitable practices in establishing authorship, and (4) upholding principles of decolonization in the education of EM trainees from LMICs and HICs. Conclusions: Understanding the colonial roots of GEM will allow us to look more critically at current health disparities and identify inequitable institutionalized practices within our profession that continue to uphold these misguided concepts. A decolonized future of GEM depends on our recognition and rectification of colonial-era practices that shape structural determinants of health care delivery and scientific advancement.

APOE ɛ4 exacerbates age-dependent deficits in cortical microstructure.

The apolipoprotein E ɛ4 allele is the primary genetic risk factor for the sporadic type of Alzheimer's disease. However, the mechanisms by which apolipoprotein E ɛ4 are associated with neurodegeneration are still poorly understood. We applied the Neurite Orientation Dispersion Model to characterize the effects of apolipoprotein ɛ4 and its interactions with age and education on cortical microstructure in cognitively normal individuals. Data from 1954 participants were included from the PREVENT-Dementia and ALFA (ALzheimer and FAmilies) studies (mean age = 57, 1197 non-carriers and 757 apolipoprotein E ɛ4 carriers). Structural MRI datasets were processed with FreeSurfer v7.2. The Microstructure Diffusion Toolbox was used to derive Orientation Dispersion Index maps from diffusion MRI datasets. Primary analyses were focused on (i) the main effects of apolipoprotein E ɛ4, and (ii) the interactions of apolipoprotein E ɛ4 with age and education on lobar and vertex-wise Orientation Dispersion Index and implemented using Permutation Analysis of Linear Models. There were apolipoprotein E ɛ4 × age interactions in the temporo-parietal and frontal lobes, indicating steeper age-dependent Orientation Dispersion Index changes in apolipoprotein E ɛ4 carriers. Steeper age-related Orientation Dispersion Index declines were observed among apolipoprotein E ɛ4 carriers with lower years of education. We demonstrated that apolipoprotein E ɛ4 worsened age-related Orientation Dispersion Index decreases in brain regions typically associated with atrophy patterns of Alzheimer's disease. This finding also suggests that apolipoprotein E ɛ4 may hasten the onset age of dementia by accelerating age-dependent reductions in cortical Orientation Dispersion Index.

The Mediterranean diet is associated with better cardiometabolic health for women in mid-life but not men: A PREVENT dementia cohort cross-sectional analysis.

BACKGROUND AND AIMS: The Mediterranean diet (MedDiet) has been associated with better cardiovascular health in a number of studies. This study aimed to explore cross-sectional associations between MedDiet adherence in the PREVENT Dementia (PREVENT) programme, stratified by sex. METHODS AND RESULTS: Three MedDiet scores were calculated (MEDAS, MEDAS continuous and Pyramid) alongside a Western diet score. We used linear regression and linear mixed effects models to test for associations between the MEDAS score and cardiovascular health. Propensity scores were calculated to strengthen causality inferences from the data, and used as covariates along with total energy intake and Western diet scores. Exploratory analysis repeated the linear regression models for each individual food component. This study included 533 participants, with a mean age 51.25 (±5.40) years, and a majority of women (60.0%). Women had higher MedDiet scores across all three scoring methods, had a lower Western diet score and consumed fewer total calories. Higher MedDiet scores were associated with lower blood pressure, body mass index (BMI) and lower cardiovascular risk scores. When stratified by sex, women had significant positive associations between MedDiet scores and lower blood pressure, BMI and glycemia, whereas men only had a significant association with lower BMI. CONCLUSION: There were significant associations between higher MedDiet scores and a number of cardiovascular health outcome measures. These associations were seen more consistently for women compared to men, which may have implications for the development of personalised nutritional recommendations to improve cardiovascular health.

Differential association of cerebral blood flow and anisocytosis in APOE ε4 carriers at midlife.

Cerebral hemodynamic alterations have been observed in apolipoprotein ε4 (APOE4) carriers at midlife, however the physiological underpinnings of this observation are poorly understood. Our goal was to investigate cerebral blood flow (CBF) and its spatial coefficient of variation (CoV) in relation to APOE4 and a measure of erythrocyte anisocytosis (red blood cell distribution width - RDW) in a middle-aged cohort. Data from 563 participants in the PREVENT-Dementia study scanned with 3 T MRI cross-sectionally were analysed. Voxel-wise and region-of-interest analyses within nine vascular regions were run to detect areas of altered perfusion. Within the vascular regions, interaction terms between APOE4 and RDW in predicting CBF were examined. Areas of hyperperfusion in APOE4 carriers were detected mainly in frontotemporal regions. The APOE4 allele differentially moderated the association between RDW and CBF, an association which was more prominent in the distal vascular territories (p - [0.01, 0.05]). The CoV was not different between the considered groups. We provide novel evidence that in midlife, RDW and CBF are differentially associated in APOE4 carriers and non-carriers. This association is consistent with a differential hemodynamic response to hematological alterations in APOE4 carriers.

Modifiable Lifestyle Activities Affect Cognition in Cognitively Healthy Middle-Aged Individuals at Risk for Late-Life Alzheimer's Disease.

BACKGROUND: It is now acknowledged that Alzheimer's disease (AD) processes are present decades before the onset of clinical symptoms, but it remains unknown whether lifestyle factors can protect against these early AD processes in mid-life. OBJECTIVE: We asked whether modifiable lifestyle activities impact cognition in middle-aged individuals who are cognitively healthy, but at risk for late life AD. Participants (40-59 years) completed cognitive and clinical assessments at baseline (N = 206) and two years follow-up (N = 174). METHODS: Mid-life activities were measured with the Lifetime of Experiences Questionnaire. We assessed the impact of lifestyle activities, known risk factors for sporadic late-onset AD (Apolipoprotein E ɛ4 allele status, family history of dementia, and the Cardiovascular Risk Factors Aging and Dementia score), and their interactions on cognition. RESULTS: More frequent engagement in physically, socially, and intellectually stimulating activities was associated with better cognition (verbal, spatial, and relational memory), at baseline and follow-up. Critically, more frequent engagement in these activities was associated with stronger cognition (verbal and visuospatial functions, and conjunctive short-term memory binding) in individuals with family history of dementia. Impaired visuospatial function is one of the earliest cognitive deficits in AD and has previously associated with increased AD risk in this cohort. Additionally, conjunctive memory functions have been found impaired in the pre-symptomatic stages of AD. CONCLUSION: These findings suggest that modifiable lifestyle activities offset cognitive decrements due to AD risk in mid-life and support the targeting of modifiable lifestyle activities for the prevention of AD.

Beyond the Basics: A Novel Approach to Integrating a Social Determinants of Health Curriculum into an Emergency Medicine Course.

Background: Our aim was to implement and evaluate a novel social determinants of health (SDoH) curriculum into the required fourth-year emergency medicine (EM) course at the University of Vermont Larner College of Medicine with the goal to teach students how to assess and address SDoH in clinical practice. The objectives were as follows: 1. Assess the SDoH, risk factors, and barriers to healthcare facing patients from diverse socioeconomic and cultural backgrounds in the ED. 2. Examine how social work consult services operate in the ED setting and how to identify appropriate referrals, resources, and treatment plans for patients in the ED. 3. Examine and interpret the impact health disparities have on patients in the ED and develop potential solutions to reduce these disparities to improve health outcomes. 4. Analyze the experiences and lessons learned and use them to inform future patient interactions. Curricular Design: The curriculum was developed by a workgroup that considered the following: scope; target learners; overall structure; instructional and delivery methods; and session scheduling. The curriculum consisted of four components that took place over the four-week EM course. Students completed a required end-of-course survey. Survey results underwent a mixed-methods analysis to assess student attitudes and the impact of the curriculum. Impact/Effectiveness: We received a 78.7% (74/94) completion rate for the 2021-2022 academic year. Of all respondents, 92% (68/74) indicated that they would apply lessons learned from the SDoH components of the curriculum; 74% (54/74) rated the SDoH curriculum as good, very good, or excellent; and 81% (60/74) felt that the EM course increased their understanding of diversity, equity, and inclusion as it relates to the practice of medicine. The thematic analyses revealed four main themes: 1) general comments; 2) course design; 3) interprofessional collaboration; and 4) expanding the scope of the curriculum. Conclusion: Social medicine integration into core EM courses is a generalizable approach to experiential and collaborative exposure to the social determinants of health. Of student respondents, 92% indicated they will use lessons learned from this curriculum in their future practice. This can improve the way future generations of physicians identify SDoH and address the social needs that affect their patients, thereby advancing and promoting health equity.

Gender-based Barriers to the Advancement of Women in Academic Emergency Medicine: A Multi-Institutional Survey Study.

INTRODUCTION: Leadership positions occupied by women within academic emergency medicine have remained stagnant despite increasing numbers of women with faculty appointments. We distributed a multi-institutional survey to women faculty and residents to evaluate categorical characteristics contributing to success and differences between the two groups. METHODS: An institutional review board-approved electronic survey was distributed to women faculty and residents at eight institutions and were completed anonymously. We created survey questions to assess multiple categories: determination; resiliency; career support and obstacles; career aspiration; and gender discrimination. Most questions used a Likert five-point scale. Responses for each question and category were averaged and deemed significant if the average was greater than or equal to 4 in the affirmative, or less than or equal to 2 in the negative. We calculated proportions for binary questions. RESULTS: The overall response rate was 55.23% (95/172). The faculty response rate was 54.1% (59/109) and residents' response rate was 57.1% (36/63). Significant levels of resiliency were reported, with a mean score of 4.02. Childbearing and rearing were not significant barriers overall but were more commonly reported as barriers for faculty over residents (P <0.001). Obstacles reported included a lack of confidence during work-related negotiations and insufficient research experience. Notably, 68.4% (65/95) of respondents experienced gender discrimination and 9.5% (9/95) reported at least one encounter of sexual assault by a colleague or supervisor during their career. CONCLUSION: Targeted interventions to promote female leadership in academic emergency medicine include coaching on negotiation skills, improved resources and mentorship to support research, and enforcement of safe work environments. Female emergency physician resiliency is high and not a barrier to career advancement.

Higher midlife CAIDE score is associated with increased brain atrophy in a cohort of cognitively healthy middle-aged individuals.

BACKGROUND: Structural brain changes associated with Alzheimer's disease (AD) can occur decades before the onset of symptoms. The Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) score has been suggested to be associated with accelerated brain atrophy in middle-aged subjects but the regional specificity of atrophic areas remains to be elucidated. METHODS: 3T T1-weighted magnetic resonance imaging scans of 160 cognitively healthy middle-aged participants (mean age = 52) in the PREVENT-Dementia cohort, from baseline and from follow-up after 2 years, were examined. Images were preprocessed using Computational Anatomy Toolbox 12. Voxel-based morphometry was performed in FSL 6.0.1 to identify areas of grey matter (GM) volume differences both cross-sectionally and longitudinally between subjects with high and low baseline CAIDE score (CAIDE score was dichotomized at cohort-median). A GM percentage of change map was created for each subject for evaluation of atrophy over 2 years. Analyses were adjusted for age, gender, education and total intracranial volume. RESULTS: Compared to subjects with CAIDE score ≤ 6 (low risk), subjects with CAIDE score > 6 (high risk) showed lower GM volume in the temporal, occipital, and fusiform cortex and lingual gyrus at baseline, and greater percentage of GM loss over 2 years in the supramarginal gyrus, angular gyrus, precuneus, lateral occipital cortex, superior parietal lobule and cingulate gyrus (corrected P < 0.05). CONCLUSION: This study demonstrated accelerated GM atrophy concentrated in several AD signature cortical regions in healthy middle-aged subjects with high CAIDE scores.

Harnessing inter-disciplinary collaboration to improve emergency care in low- and middle-income countries (LMICs): results of research prioritisation setting exercise.

BACKGROUND: More than half of deaths in low- and middle-income countries (LMICs) result from conditions that could be treated with emergency care - an integral component of universal health coverage (UHC) - through timely access to lifesaving interventions. METHODS: The World Health Organization (WHO) aims to extend UHC to a further 1 billion people by 2023, yet evidence supporting improved emergency care coverage is lacking. In this article, we explore four phases of a research prioritisation setting (RPS) exercise conducted by researchers and stakeholders from South Africa, Egypt, Nepal, Jamaica, Tanzania, Trinidad and Tobago, Tunisia, Colombia, Ethiopia, Iran, Jordan, Malaysia, South Korea and Phillipines, USA and UK as a key step in gathering evidence required by policy makers and practitioners for the strengthening of emergency care systems in limited-resource settings. RESULTS: The RPS proposed seven priority research questions addressing: identification of context-relevant emergency care indicators, barriers to effective emergency care; accuracy and impact of triage tools; potential quality improvement via registries; characteristics of people seeking emergency care; best practices for staff training and retention; and cost effectiveness of critical care - all within LMICs. CONCLUSIONS: Convened by WHO and facilitated by the University of Sheffield, the Global Emergency Care Research Network project (GEM-CARN) brought together a coalition of 16 countries to identify research priorities for strengthening emergency care in LMICs. Our article further assesses the quality of the RPS exercise and reviews the current evidence supporting the identified priorities.

Midlife alcohol consumption and longitudinal brain atrophy: the PREVENT-Dementia study.

BACKGROUND AND AIMS: Consensus is lacking on whether light to moderate consumption of alcohol compared to abstinence is neuroprotective. In this study, we investigated the relationship between self-reported alcohol use and brain volume change over 2 years in middle-aged subjects. METHODS: A sample of 162 subjects (aged 40-59 at baseline) from the PREVENT-Dementia programme underwent MRI scans on two separate occasions (mean interval 734 days; SD 42 days). We measured longitudinal rates of brain atrophy using the FSL Siena toolbox, and change in hippocampal volume from segmentation in SPM. RESULTS: Controlling for age and sex, there were no significant associations of either total brain, ventricular, or hippocampal volume change with alcohol consumption. Adjusting for lifestyle, demographic and vascular risk factors did not alter this. CONCLUSIONS: We did not find any evidence of influence of alcohol consumption on changes in brain volume over a 2-year period in 40-60-year-olds.

Regional hyperperfusion in cognitively normal APOE ε4 allele carriers in mid-life: analysis of ASL pilot data from the PREVENT-Dementia cohort.

BACKGROUND: Regional cerebral hypoperfusion is characteristic of Alzheimer's disease (AD). Previous studies report conflicting findings in cognitively normal individuals at high risk of AD. Understanding early preclinical perfusion alterations may improve understanding of AD pathogenesis and lead to new biomarkers and treatment targets. METHODS: 3T arterial spin labelling MRI scans from 162 participants in the PREVENT-Dementia cohort were analysed (cognitively normal participants aged 40-59, stratified by future dementia risk). Cerebral perfusion was compared vertex-wise according to APOE ε4 status and family history (FH). Correlations between individual perfusion, age and cognitive scores (COGNITO battery) were explored. RESULTS: Regional hyperperfusion was found in APOE ε4+group (left cingulate and lateral frontal and parietal regions p<0.01, threshold-free cluster enhancement, TFCE) and in FH +group (left temporal and parietal regions p<0.01, TFCE). Perfusion did not correlate with cognitive test scores. CONCLUSIONS: Regional cerebral hyperperfusion in individuals at increased risk of AD in mid-life may be a very early marker of functional brain change related to AD. Increased perfusion may reflect a functional 'compensation' mechanism, offsetting the effects of early neural damage or may itself be risk factor for accelerating spread of degenerative pathology.

Hippocampal Subfield Volumes in Middle-Aged Adults at Risk of Dementia.

BACKGROUND: Alzheimer's disease (AD) begins decades before the onset of dementia. There is a need to investigate biomarkers of early AD for use in clinical trials and to facilitate early intervention. OBJECTIVE: We aimed to determine whether changes in hippocampal subfield volumes in healthy middle-aged adults were associated with risk of future dementia. METHODS: We included 150 participants from the PREVENT-Dementia cohort, which recruited subjects aged 40-59 with or without a family history of dementia (FHD; included here were 81 with FHD and 69 without). Hippocampal subfield volumes were segmented from high resolution T2-weighted 3T MRI images taken at baseline and 2-year follow-up. RESULTS: FHD and greater 20 year-risk of dementia due to cardiovascular risk factors were both associated with lower CA1 volume. FHD was also associated with a relative increase in combined CA3, CA4, and dentate gyrus volume between baseline and follow-up. CONCLUSION: CA1 atrophy may commence as early as middle-age in those with a high risk of future dementia, while increases in CA3, CA4, and dentate gyrus volume may be a response to early AD in the form of inflammation or neurogenesis.

Volumetric alterations in the hippocampal subfields of subjects at increased risk of dementia.

The hippocampus is one of the first regions to demonstrate atrophy during the prodromal stage of Alzheimer's disease. Volumetric analysis of its individual subfields could provide biomarkers with higher sensitivity than whole hippocampal volume during an earlier disease stage. We quantified the hippocampal subfields volume in a large cohort comprising healthy participants (aged 40-59) with dementia family history (FH) and controls (without FH), examined at 2 time points across 2 years. Subfield volumes were quantified using both a T1-weighted and a high-resolution T2 hippocampal magnetic resonance imaging acquisition with Freesurfer. The participants were stratified based on dementia FH, APOE genotype, and CAIDE (Cardiovascular Risk Factors, Aging and Dementia) risk score. Whole hippocampal volume did not differ between the groups. The volume of the molecular layer was lower in participants with an APOE ε4 genotype, but there were no differences between subjects with and without dementia FH or with an increasing CAIDE score. The molecular layer may be the first hippocampal region to demonstrate volumetric alterations in subjects at risk of dementia.

Association between midlife dementia risk factors and longitudinal brain atrophy: the PREVENT-Dementia study.

BACKGROUND: Increased rates of brain atrophy on serial MRI are frequently used as a surrogate marker of disease progression in Alzheimer's disease and other dementias. However, the extent to which they are associated with future risk of dementia in asymptomatic subjects is not clear. In this study, we investigated the relationship between the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) risk score and longitudinal atrophy in middle-aged subjects. MATERIALS AND METHODS: A sample of 167 subjects (aged 40-59 at baseline) from the PREVENT-Dementia programme underwent MRI scans on two separate occasions (mean interval 735 days; SD 44 days). We measured longitudinal rates of brain atrophy using the FSL Siena toolbox. RESULTS: Annual percentage rates of brain volume and ventricular volume change were greater in those with a high (>6) vs low CAIDE score-absolute brain volume percentage loss 0.17% (CI 0.07 to 0.27) and absolute ventricular enlargement 1.78% (CI 1.14 to 2.92) higher in the at risk group. Atrophy rates did not differ between subjects with and without a parental history of dementia, but were significantly correlated with age. Using linear regression, with covariates of age, sex and education, CAIDE score >6 was the only significant predictor of whole brain atrophy rates (p=0.025) while age (p=0.009), sex (p=0.002) and CAIDE>6 (p=0.017) all predicted ventricular expansion rate. CONCLUSION: Our results show that progressive brain atrophy is associated with increased risk of future dementia in asymptomatic middle-aged subjects, two decades before dementia onset.

Research participants as collaborators: Background, experience and policies from the PREVENT Dementia and EPAD programmes.

AIM: Despite the growing importance of public and patient involvement in biomedical research, comparatively little attention has been paid to the important role of research participants themselves. Our aim in this paper is to explore the impact research participant involvement has within the PREVENT and the European Prevention of Alzheimer's Dementia (EPAD) projects. METHOD: In this paper, we report the experiences of involving research participants as collaborators in prospective cohort studies exploring early changes in the brain as pathways towards and risks for dementia. We use minutes and feedback from members of the panel and steering committee to understand the experience and impact on the study. RESULTS: We describe the aims and structure of the participant panel established within the PREVENT Dementia study and highlight its contributions to the organisation, conduct and future of the study. Key areas of contribution identified include recruitment, inclusion of additional sub-studies, understanding the participant experience and contributing to the future of the study. DISCUSSION: We then describe how the PREVENT Dementia panel forms the basis for participant involvement within EPAD project.

At, with and beyond risk: expectations of living with the possibility of future dementia.

Biomedical research aimed at the development of therapies for chronic and late-onset conditions increasingly concentrates on the early treatment of symptom-less disease. This broad trend is evidenced in prominent shifts in contemporary dementia research. Revised diagnostic criteria and new approaches to clinical trials propose a focus on earlier stages of disease and prompt concerns about the implications of communicating test results associated with the risk of developing dementia when no effective treatments are available. This article examines expectations of the implications of learning test results related to dementia risk, based on focus group research conducted in the UK and Spain. It points to the extended social and temporal aspects of the dementia risk experience. Three key dimensions of this risk experience are elaborated: living 'at risk', represented in efforts to reduce risk and plan for the future; 'with risk', through vigilance towards cognitive health and earlier or prolonged contact with healthcare services; and finally, 'beyond risk' through a cessation of the self in its current social, legal and financial form. A virtual abstract of this paper can be viewed at: https://www.youtube.com/channel/UC_979cmCmR9rLrKuD7z0ycA.

Perspectives on Communicating Biomarker-Based Assessments of Alzheimer's Disease to Cognitively Healthy Individuals.

In clinical trials which target pathophysiological mechanisms associated with Alzheimer's disease, research participants who are recruited based on biomarker test results should be informed about their increased risk of developing Alzheimer's dementia. This paper presents the results of a qualitative focus group study of attitudes and concerns toward learning information about biomarker-based risk status among healthy research participants in the United Kingdom and Spain and people with dementia and their supporters/caregivers from countries represented in the European Working Group of People with Dementia of Alzheimer Europe. The study identified expectations related to learning risk status and preferences related to the content, quality, and follow-up of the disclosure process. The latter emphasize distinctions between risk and diagnoses, the importance of clear information about risk, and suggestions for risk reduction, as well as expectations for follow up and support. The implications of these preferences for practice are discussed. Providing details of research participants' experience and views may serve as a guide for the development of processes for the responsible disclosure of Alzheimer's disease biomarkers.

Cerebral small vessel disease in middle age and genetic predisposition to late-onset Alzheimer's disease.

INTRODUCTION: Cerebral small vessel disease (CSVD) is associated with late-onset Alzheimer's disease (LOAD) and might contribute to the relationship between apolipoprotein E ε4 (APOE ε4) and LOAD, in older people. However, it is unclear whether CSVD begins in middle age in individuals genetically predisposed to LOAD. METHODS: We assessed the relationship between radiological markers of CSVD, white matter hyperintensities and microbleeds, and genetic predisposition to LOAD in a cross-sectional analysis of cognitively normal subjects aged 40-59 years recruited from the PREVENT Dementia study. RESULTS: Microbleed prevalence was 14.5%, and mean ± standard deviation white matter hyperintensity percentage of total brain volume was 0.41 ± 0.28%. There was no significant association between APOE ε4 carrier status or history of parental dementia and white matter hyperintensity volume (P = .713, .912 respectively) or microbleeds (P = .082, .562 respectively) on multiple regression. DISCUSSION: Genetic predisposition to LOAD, through APOE genotype or AD family history, is not associated with CSVD in middle age.