Extreme heat is intensifying globally and disproportionately harms people experiencing homelessness, who face continuous exposure and limited capacity to access cooling. We reviewed the literature on heat-protection interventions that report findings for people experiencing homelessness. Only 12 studies met the inclusion criteria, indicating a sparse and heterogeneous evidence base mainly from high-income countries (USA, Canada, and Australia). No eligible studies were identified from Europe despite substantial heat events in the region. Interventions included cooling centres and cooled public spaces (eg, air-conditioned community halls and libraries), outreach and preparedness programmes (eg, education and weather-preparedness kits), and makeshift shelter modifications (eg, tent shading and ventilation), with housing and temporary accommodation discussed as structural protection. Access barriers to cooled spaces were common (eg, transport constraints and rules restricting belongings or pets), and some participants relied on self-directed cooling strategies (eg, travelling on public transport) rather than services. Evaluations reported qualitative implementation outcomes and physiological and exposure outcomes, with limited clinical-outcome reporting, constraining inference about effects on heat-related morbidity or mortality. Future research should prioritise co-designed, hybrid models that combine accessible cooling centres and cooled public spaces with outreach and low-cost mobile or distributed cooling (eg, electric fans and water dousing), evaluated using standardised implementation metrics and broad health endpoints.
BACKGROUND:Understanding the size, gender composition, and cadre mix of the health workforce and how it has evolved across time and locations can inform policies for planning, recruitment, training, and retention of human resources for health (HRH), and improvement of access to the health-care workforce among populations. Using comparable and standardised data sources, we aim to describe the composition and density of health workers by sex among 20 cadres for 204 countries and territories over 1990-2023 and quantify workforce shortfalls relative to universal health coverage (UHC) attainment. METHODS:We used 1816 country-years of data from population-based surveys, 82 from censuses, 3888 from administrative sources, and 96 from scientific literature. We harmonised reported occupation in all sources with the International Standard Classification of Occupations 2008. We produced estimates for 20 cadres and the total health workforce disaggregated by sex using spatiotemporal Gaussian process regression, a standardised method in the Global Burden of Diseases, Injuries, and Risk Factors study. Finally, stochastic frontier meta-regression was used to estimate the minimum density of doctors, nurses and midwives, dentists, and pharmacists required to reach a score of 80 out of 100 on the UHC effective coverage index. FINDINGS:In 2023, there were 122·1 million (95% uncertainty interval 115·4-130·5) health workers across 20 cadres, an increase of 81·2 million (72·0-90·5) or 198·5% (161·9-245·6) relative to 1990. Of that total, there were 15·1 million (13·1-18·2) doctors, 33·2 million (30·8-36·3) nurses, 2·4 million (2·0-2·9) midwives, and 7·6 million (6·7-8·6) community health workers (CHWs). 68·9% (66·9-70·6) of all health workers in 2023 were female, and female health workers accounted for 71·4% (64·5-77·4) of net HRH workforce growth. Less than half of doctors were female (43·9%, 34·5-53·2) and most nurses (80·7%, 76·2-83·1), midwives (96·0%, 83·9-98·5), and CHWs (89·5%, 83·6-93·7) were female. Substantial differences in HRH density remained into 2023: sub-Saharan Africa had the lowest HRH densities across cadres, with the exception of CHWs, while high-income countries had the highest HRH densities. To reach 80 out of 100 on the UHC index, an additional 7·1 million (6·6-7·5) doctors, 23·9 million (21·8-26·1) nurses and midwives, 1·8 million (1·6-1·9) dentists, and 1·6 million (1·4-1·9) pharmacists are required globally. INTERPRETATION:The global health workforce has expanded substantially since 1990, largely due to women entering the formal health workforce. However, this expansion has been uneven across regions and persistent shortfalls remain in doctors, nurses and midwives, dentists, and pharmacists relative to moderate UHC attainment. Addressing these gaps will require expansion of training capacity, retention and remuneration policies for early-career workers, and gender-responsive workforce arrangements. FUNDING:Gates Foundation.
BACKGROUND:WHO's Global Oral Health Action Plan (GOHAP) targets include a 10% relative reduction in the combined prevalence of main oral conditions by 2030. The first GOHAP evaluation was planned for 2023, with subsequent evaluations scheduled for 2026 and 2030. The aim of this systematic analysis of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 was to evaluate global and regional progress (2019-23) towards this target and related complementary indicators. METHODS:Using modelled estimates from epidemiological surveys and registries in 204 countries and territories, we estimated the age-standardised prevalence of untreated caries in deciduous and permanent teeth, severe periodontitis, edentulism, other oral disorders and orofacial clefts, and the age-standardised incidence of lip and oral cavity cancer. Progress towards GOHAP targets was measured by comparing the percentage change from 2019 to 2023 in the above indicators against the stated GOHAP target of a 10% relative reduction. FINDINGS:Globally, the age-standardised prevalence of main oral conditions declined (-1·55% [95% uncertainty interval -2·32 to -0·82]) between 2019 and 2023, but global cases increased by 3·07% (2·32 to 3·75), from 3·62 billion (3·35 to 3·95) to 3·73 billion (3·45 to 4·06). Among complementary indicators, reductions in age-standardised prevalence were observed for untreated caries in permanent teeth (-1·99% [-2·49 to -1·40]) whereas the age-standardised incidence of lip and oral cavity cancer increased (8·35% [0·13 to 16·32]), as did the age-standardised prevalence of orofacial clefts (2·25% [0·77 to 3·83]). Progress was heterogeneous across GBD super-regions, with south Asia having the largest reductions in the age-standardised prevalence of main oral conditions (-3·34% [-4·95 to -1·80]) and untreated caries in deciduous teeth (-9·09% [-17·62 to -0·08]). Sub-Saharan Africa showed the largest increase in prevalent cases of main oral conditions (9·51% [8·09-10·94]) and age-standardised incidence of lip and oral cavity cancer (14·86% [1·19-32·45]). The high-income super-region had an increase in the age-standardised prevalence of main oral conditions (1·24% [0·56-1·96]) and untreated caries in deciduous teeth (9·21% [6·60-11·89]). INTERPRETATION:Our modelled estimates of global trends in the prevalence of oral conditions from 2019 to 2023 suggest that early progress is modest and, at the current pace, insufficient to meet the 2030 GOHAP targets. Accelerated, equity-focused prevention and integration of essential oral health-care services within primary care and universal health coverage are needed, alongside strengthened oral cancer control and congenital anomaly care. FUNDING:The Gates Foundation.
The public health approach to suicide prevention recognises the importance of maintaining a whole-of-government policy focus. In many countries, this focus is achieved through the planning and implementation of a national suicide prevention strategy (NSPS). Evidence on the outcomes associated with NSPSs is, however, both scarce and inconsistent. In this Health Policy, we identify and review 26 studies that provide quantitative data on changes in the incidence of suicidal behaviour associated with the introduction of a NSPS. We found that reductions in suicide rates were observed in several countries, but there were also countries where there was no change or even an increase in the suicide rate. Moreover, multiple studies of the same NSPS and multiple iterations of a NSPS within the same country produced discrepant findings. Additionally, there are differences in research design and risk of bias between studies. We identified several methodological limitations (including threats to both internal and external validity) linked to the non-recognition of NSPS as a complex intervention. Finally, we propose a realist approach to evaluation as the keystone of a mixed-methods, multilevel research design for NSPS evaluation studies that does justice to the characteristics and complexity of the phenomenon under investigation.
BACKGROUND:How specific physical illnesses differentially contribute to the persistent mortality gap in severe mental illness (including schizophrenia spectrum disorders, bipolar disorder, and major depressive disorder) remains poorly understood. Using a harmonised multi-country design, we aimed to analyse excess mortality across diagnoses and causes of death to identify high-burden and high-inequity mortality patterns to inform public health prioritisation and organisation of care. METHODS:In this population-based multi-country cohort study using national health registers, we identified people diagnosed with severe mental illness at age 15-65 years in five European countries (Denmark, Finland, France, Poland, and Sweden) during 2004-23 to establish excess mortality before age 75 years in relation to country-specific general population mortality. We defined cause-specific mortality using ICD-10. Random effects meta-analysis was used to pool mortality estimates representing country-specific relative mortality inequities (sex-standardised and age-standardised mortality ratios), absolute excess burden (sex-standardised and age-standardised death rates per 10 000 person-years), and the severity of premature mortality (potential years-of-life-lost before age 75 years). Subgroup analyses were conducted to test for potential effect modification. FINDINGS:Between Jan 1, 2004, and Dec 31, 2023, there were 4 861 795 people with severe mental illness, and 561 903 deaths from any cause. All-cause mortality was 2·6-fold higher in people with severe mental illness compared with the general population (pooled standardised mortality ratio [SMR] 2·64, 95% CI 2·25-3·11). Absolute excess mortality was highest in cardiovascular disease (schizophrenia spectrum disorders: standardised excess death rate 22·08 per 10 000 person-years, 95% CI 8·77-35·39; bipolar disorder: 8·36 per 10 000 person-years, 2·96-13·75; and major depressive disorder: 9·82 per 10 000 person-years, 3·18-16·45). Relative excess mortality was highest in respiratory diseases (schizophrenia spectrum disorders: SMR 6·49; 95% CI 5·52-7·64; bipolar disorder: 2·72, 2·04-3·63; and major depressive disorder: 3·48, 2·63-4·62), followed by endocrine and metabolic diseases (schizophrenia spectrum disorders: 5·09, 4·29-6·04; bipolar disorder: 2·60, 2·26-2·98; and major depressive disorder: 3·07, 1·84-5·12), and in gastrointestinal diseases (schizophrenia spectrum disorders: 3·47, 2·58-4·67; bipolar disorder: 2·34, 2·00-2·74; and major depressive disorder: 3·48, 2·63-4·62). INTERPRETATION:The mortality gap was characterised by distinct patterns of absolute excess mortality and relative inequality across causes of death and severe mental illness diagnoses. Considering both dimensions of excess mortality can inform public health priorities that are not apparent from either measure alone or from focusing on cause-specific numbers of deaths. Reducing premature mortality will therefore require an integrated public health approach that combines universal strategies with targeted interventions to address both high-burden causes of death and those characterised by the greatest relative inequalities. FUNDING:2024 European Partnership on Transforming Health and Care Systems.
Background Over 20% of Europe's population is chronically exposed to transport noise levels considered detrimental to health, yet evidence on its impact on children's mental health remains limited. We aimed to investigate the effect of different sources of residential noise exposure on children's emotional and behavioural difficulties. Methods In this birth cohort study, data from the nationally representative French ELFE cohort were analysed from birth to age 10 years (2011–22). We excluded children with missing data on the study's exposures from age 2 months to 5·5 years and on outcome variables at age 10·5 years, twins, children in foster care, and children with profound hearing impairment. Residential exposure to road traffic, aircraft, and railway noise was assessed at age 2 months, 3·5 years, and 5·5 years using GeoClimate and NoiseModelling open-source software and public geographical, traffic, and noise map data. Children's mental health was assessed using the parent-reported Strengths and Difficulties Questionnaire at age 10·5 years. We applied marginal structural models with inverse probability weighting to estimate the effect of time-varying noise exposure through childhood. Findings Of the 7914 children included, 4044 (51·1%) were male and 3870 (48·9%) were female. At age 2 months, 2480 (31·3%) children were exposed to low levels (<55 A-weighted decibels [dB(A)]) of road traffic noise exposure, 2772 (35·0%) were exposed to medium levels (55–<60 dB[A]), and 2662 (33·6%) were exposed to high levels (≥60 dB[A]). Persistent exposure to high levels of road traffic noise (≥60 dB[A] across childhood) was associated with higher levels of internalising symptoms at age 10·5 years (adjusted regression coefficient β=0·38, 95% CI 0·14 to 0·63; p=0·003), particularly emotional symptoms (β=0·20, 0·02 to 0·37; p=0·026) and peer relationship problems (β=0·19, 0·06 to 0·32; p=0·009). No significant effects were detected for high exposure to road traffic noise at age 3·5 years. At age 2 months, 161 (2·0%) children were exposed to railway noise of 50 dB(A) or higher. Exposure to railway noise (at least once to ≥50 dB[A] during childhood) was associated with lower levels of internalising symptoms (β=–0·61, 95% CI –1·10 to –0·12; p=0·008), although this association was no longer significant after correction for multiple testing. Exposure to aircraft noise was low, with 185 (2·3%) children exposed to 50 dB(A) or higher at age 2 months, and no significant associations were observed between exposure to aircraft noise and children's emotional and behavioural difficulties. Interpretation Although residual confounding cannot be entirely excluded, our results support the need for policies aimed at reducing residential road traffic noise. They require replication in other large-scale cohorts and further investigation of the underlying mechanisms is needed. Funding None.
Background Ensuring appropriate access to essential antibiotics is a crucial public health goal. The 2024 UN General Assembly agreed that 70% of global antibiotic use should be from the Access group of the WHO Access, Watch, Reserve (AWaRe) system. A standard method to estimate optimal national-level antibiotic use based on burden of disease, resistance, and local context is needed to inform national policies. We aimed to develop and apply a burden-adjusted framework for estimating expected optimal national levels of AWaRe antibiotic use, in total and by AWaRe group. Methods We used data from multiple global sources—including datasets from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021; the Global Research on Antimicrobial Resistance project; and the World Bank—to cluster 186 countries, territories, and areas (CTAs) into four peer groups on the basis of sociodemographic factors, infection burden, and resistance incidence using a latent class model. Within each cluster, we identified benchmark CTAs with low antibiotic use and low infection mortality. For each CTA, we used the infection burden to estimate the optimal total defined daily doses (DDD) per 1000 inhabitants per day (DID) for 2019. We then estimated optimal Reserve DID on the basis of relevant resistance burdens, optimal Watch DID from the number of infections requiring Watch antibiotics as defined in the WHO AWaRe antibiotic book, and optimal Access DID as the remaining volume after accounting for Watch and Reserve antibiotic needs. Where CTA-level data on actual antibiotic use in 2019 were available in the IQVIA MIDAS database, estimated optimal levels were compared with actual levels, in total and by AWaRe group. Findings We estimated that, in 2019, 43·0 billion DDD (95% CI 35·4 billion–57·7 billion) of antibiotics were needed in 186 CTAs, of which 77% (95% CI 71–83) would optimally be from the Access group. CTAs in lower-income clusters required more Watch and Reserve antibiotics than higher-income CTAs: at optimal use levels, 81·7% (80·3–82·9) of global Watch antibiotic need and 80·7% (95% CI 68·5–88·9) of global Reserve antibiotic need would arise from the two lowest-income clusters. Among 67 CTAs with actual antibiotic use data available, 48 (72%) used higher total antibiotic volumes than were estimated optimal. Overuse was most frequent in high-income settings: 33 (87%) of 38 CTAs in the highest-income cluster exceeded the estimated optimal total DID. 66 (99%) of 67 CTAs used more Watch antibiotics than optimal, whereas 36 (54%) used lower volumes of Reserve antibiotics and 28 (42%) used lower volumes of Access antibiotics than were estimated optimal. Interpretation We present estimates for optimal AWaRe antibiotic use for 186 CTAs. After accounting for CTA-specific needs, the UN General Assembly's target of 70% of global antibiotic use being from the Access group seems globally appropriate. Benchmarking the use of AWaRe antibiotics enables estimates of their underuse and overuse in individual CTAs, helping to inform national policies. Funding The Antibiotic Data to Inform Local Action (ADILA) Project, funded by the Wellcome Trust.
Background As survival improves globally, the central public health challenge increasingly shifts from extending life to extending healthy lifespan. The compression of morbidity hypothesis proposes that effective prevention and care will delay disability more than death, reducing the morbidity gap—ie, the duration or proportion of life spent in poor health. We aimed to comprehensively estimate changes in the morbidity gap globally, regionally, and nationally from 1990 to 2023, by sociodemographic development levels and sex, and analysed leading diseases and injuries and their underlying risk factors contributing to years lived in poor health. Methods Using Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 estimates of life expectancy and healthy life expectancy (HALE) at birth for 204 countries and territories from 1990 to 2023, we calculated the morbidity gap as life expectancy minus HALE, and the proportional morbidity gap as this difference divided by life expectancy. Results are presented globally, by GBD super-region and country, Socio-demographic Index (SDI) quintile, and sex. We decomposed the morbidity gap into cause-specific and risk-specific contributions, assigning to each cause group its proportional share of years lived with disability (YLD), adjusted for comorbidity to avoid double counting disability for co-occurring conditions. We report mean estimates and 95% uncertainty intervals (UIs) derived from 250 or more draws from posterior distributions. Findings From 1990 to 2023, the global morbidity gap increased from 8·8 years (95% UI 6·7–11·2) to 10·7 (8·2–13·7), an increase of 1·9 years (1·3–2·6), or 21·9% (16·0–27·9), with point estimates suggesting widening morbidity gaps in 203 of 204 countries and territories. Globally in 2023, an average of 14·5% of life was spent in poor health, compared to 13·6% in 1990. From 1990 to 2023, across locations, age-specific morbidity gaps widened across the adult life course, rather than concentrating in the final years of life. In 2023, morbidity gaps were largest in the high SDI quintile and smallest in the low SDI quintile. Countries with longer life expectancies had larger morbidity gaps and both had a positive relationship with SDI; however, the relationship between life expectancy and the proportional morbidity gap was less clear. A small number of chronic, largely non-fatal causes were the primary contributors to the morbidity gap, with musculoskeletal disorders (especially low back pain), mental disorders (depressive and anxiety disorders), sense organ diseases (age-related hearing loss), unintentional injuries (falls), and other non-communicable diseases together accounting for 57·4% of unhealthy years in 2023, globally. High fasting plasma glucose, high body-mass index, and child and maternal malnutrition were the leading risk factors contributing to the global morbidity gap. Interpretation The expansion of the morbidity gap across nearly all locations indicates that improvements in survival have consistently outpaced reductions in non-fatal health loss across geographies, SDI levels, and sexes, with most populations now spending a decade or more of life in poor health across the lifespan. Progress towards healthy ageing should therefore be assessed not only by reduced mortality, but also by declines in years lived in poor health, with emphasis placed on extending healthspan. Funding The Gates Foundation.
BACKGROUND:Road injuries are a leading cause of mortality and morbidity worldwide. Years of international efforts have aimed to strengthen policy engagement, including the 2020 UN General Assembly's proclamation of the Second Decade of Action for Road Safety (2021-30), targeting a 50% reduction in road traffic deaths and serious injuries by 2030. The aim of this study is to provide estimates to monitor progress and identify intervention gaps. METHODS:As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2023, we estimated incidence, mortality, and morbidity of road injuries for 204 countries and territories from 1990 to 2023. Four road injury types and 47 nature-of-injury categories were examined. Morbidity and mortality data from clinical records, vital registration, and police reports were harmonised using meta-analytic techniques to ensure consistency and correct for systematic bias. Incidence was modelled with the meta-regression tool Disease Modelling-Meta-Regression version 2.1 and cause-specific mortality with the Cause of Death Ensemble model, both incorporating location-specific covariates to support interpolation. Years of life lived with disability (YLDs) were estimated from the prevalence and severity of the nature of road injury, and years of life lost (YLLs) from the number of cause-specific deaths multiplied by the standard life expectancy at the age of death. Disability-adjusted life-years (DALYs) were the sum of YLLs and YLDs. All metrics were calculated with 95% uncertainty intervals (UIs). FINDINGS:In 2023, there were 50·9 million (95% UI 46·1-56·1) road injury incident cases, 1·34 million (1·04-1·58) deaths, and 75·3 million (59·8-89·2) DALYs globally. Road injuries were the leading global cause of death among males aged 10-39 years. Between 1990 and 2023, age-standardised incidence decreased by 38·3% (95% UI 36·9-39·7) and mortality decreased by 32·3% (6·1-49·0), but progress varied widely by World Bank income group. Mortality in low-income countries (43·8 [95% UI 31·7-56·0] deaths per 100 000 population) was approximately six times higher than in high-income countries (7·5 [7·1-7·9] deaths per 100 000), despite the high-income countries showing the highest age-standardised incidence rates (858·1 [95% UI 781·9-947·1] cases per 100 000). In the past decade, many countries achieved notable reductions in road injuries, but others, including Ghana and the USA, saw increases. More severe injuries tended to occur in low-income and middle-income countries. INTERPRETATION:Although global incidence, mortality, and DALY rates from road injuries have declined, progress remains uneven, with pronounced disparities across income groups reflecting systemic inadequacies in infrastructure, vehicle standards, enforcement, and post-crash care. Strengthening emergency response, improving road design, enforcing safety measures, and adapting policies to the evolving demographics remain essential. FUNDING:Gates Foundation.
BACKGROUND:Although global estimates for dementia risk reduction are available, risk profiles might differ in a high-income, welfare-state setting. Few studies have been conducted that simultaneously estimate the prevalence of dementia risk factors and their associated risk of dementia within the same nationwide population. We aimed to estimate the relative risk of dementia and the population attributable fractions (PAFs) for 16 potentially modifiable risk factors, their combinations, and their interactions based on routinely collected health registry and survey data. METHODS:We conducted a nationwide cohort study based on data from Danish registries and the Danish National Health Survey (DNHS). The whole population, which included individuals born in or before 1957 who were alive, living in Denmark, and dementia-free at the start of follow-up, was followed up from age 65 years, or Jan 1, 2010 (whichever came last); individuals with additional data from the DNHS formed a subpopulation. Follow-up ended at death, emigration, dementia diagnosis, or on Dec 31, 2022 (whichever came first). The primary outcome was incident all-cause late-onset dementia diagnosis (age ≥65 years). We calculated dementia hazard ratios and PAFs for 16 risk factors (depression, traumatic brain injury, hospital-diagnosed infections, vision impairment, cardiovascular disease, sleep disorders, diabetes, hearing loss, hypercholesterolaemia, low education, hypertension, physical inactivity, social isolation, smoking, alcohol consumption, and obesity), as well as their combinations, and interactions between risk factors. Analyses were stratified by sex, birth cohorts, and educational level. Sensitivity analysis included accounting for reverse causation by splitting the risk time into less than 5 years and more than 5 years since exposure. FINDINGS:The whole population comprised 1 753 515 individuals, of whom 194 368 had additional DNHS data. The overall PAF for dementia in Denmark was 37·8% (95% CI 35·6-40·0) for the assessed risk factors. PAF for individual risk factors was highest for hospital-diagnosed infections (9·4% [9·3-9·4]), depression (8·7% [8·6-8·8]), and cardiovascular disease (CVD; 7·6% [7·6-7·7]). After accounting for reverse causation, the PAF for hospital-diagnosed infections was 7·0% (95% CI 6·9-7·0), and 5·7% (5·7-5·8) for depression. The apparently protective effect of obesity on dementia was also shown to be driven by reverse causation. The overall PAF was higher in males, 1948-57 birth cohorts, and individuals with low education. Risk factor profiles varied by sex and birth cohorts. Risk factor combinations involving depression, hospital-diagnosed infections, or CVD showed the strongest superadditive effects. Interactions between some risk factors were seen in only some of the studied subgroups (eg, in the 1948-57 birth cohorts and individuals with low education). INTERPRETATION:These findings reinforce the need for tailored dementia interventions building on country-specific evidence. Our findings on interactions between different risk factors are important for generating novel hypotheses on the mechanisms underlying dementia disorders and highlighting at-risk population groups for whom targeting of one risk factor could reduce the risk associated with the co-occurring factor. FUNDING:The Alzheimer-forskningsfonden, the KID foundation, and the Danish Ministry of Health.
BACKGROUND:Previous cohort studies of physical activity and cognitive health have often been limited by small sample sizes, short follow-up durations, absence of long-term assessments of physical activity, and potential reverse causation. We aimed to prospectively examine the associations between long-term physical activity and multiple cognitive outcomes. METHODS:In this study, we used data from two ongoing US prospective cohorts: the Nurses' Health Study (established in 1976, comprising 121 700 female registered nurses aged 30-55 years at enrolment) and the Health Professionals Follow-Up Study (HPFS; established in 1986, comprising 51 492 male health professionals aged 40-75 years at enrolment). Discretionary physical activity was assessed approximately every 2-4 years using self-report questionnaires, beginning in 1986 for both cohorts. Total physical activity, walking, and vigorous aerobic exercise were each expressed as the summed metabolic equivalent of task hours per week. We ascertained incident dementia cases (a composite endpoint of self-reported physician-diagnosed dementia and deaths due to dementia) in eligible Nurses' Health Study participants (1990-2023) and HPFS participants (1990-2023); deaths due to dementia were confirmed using medical records, death certificates, and autopsy reports. Objective cognitive function was assessed in Nurses' Health Study participants only (1995-2008) using the Telephone Interview for Cognitive Status (TICS). Subjective cognitive decline was self-reported by Nurses' Health Study participants (followed up in 2012 and 2014) and HPFS participants (followed up in 2008, 2012, 2016, 2018, and 2020) via questionnaires with binary questions that assessed subjective cognitive concerns across multiple domains. Participants were excluded from the analysis if they had dementia, stroke, cancer, were missing total physical activity or walking data, or reported difficulties with walking at baseline. Outcomes were analysed using multivariable-adjusted regression models. We used a 4-year lag approach in our main analyses to minimise the potential for reverse causation. FINDINGS:Our final samples comprised 63 596 Nurses' Health Study participants and 43 440 HPFS participants for the dementia endpoints, 13 647 Nurses' Health Study participants for assessing objective cognitive function, and 29 801 Nurses' Health Study participants and 17 162 HPFS participants for assessing subjective cognitive decline. Compared with participants in the lowest quartile for total physical activity, those in the highest quartile had a lower risk of dementia (hazard ratio [HR] 0·72, 95% CI 0·68-0·76; p<0·0001 for trend) and subjective cognitive decline (relative risk [RR] 0·77, 95% CI 0·73-0·80; p<0·0001 for trend). Being in the highest versus the lowest tertile for walking or vigorous aerobic exercise was also associated with lower risk for dementia (HR 0·76, 95% CI 0·72-0·80 for walking and 0·89, 0·85-0·93 for vigorous aerobic exercise; p<0·0001 for trend for both activities) and subjective cognitive decline (RR 0·82, 95% CI 0·79-0·86 for walking and 0·89, 0·86-0·93 for vigorous aerobic exercise; p<0·0001 for trend for both activities). Additionally, being in the highest quartile of total physical activity versus the lowest quartile was associated with fewer years of age-related cognitive differences in global cognition (mean difference -1·15, 95% CI -1·69 to -0·60; p<0·0001 for trend), verbal memory (-1·27, -1·86 to -0·68; p<0·0001 for trend), and TICS score (-0·79, -1·36 to -0·23; p=0·016 for trend). Similar decreases were observed for vigorous aerobic exercise but not for walking. INTERPRETATION:Higher levels of physical activity were associated with a lower risk of dementia and better cognitive performance. These findings support physical activity as a potential strategy to promote long-term cognitive health. FUNDING:US National Institutes of Health.
Alzheimer's disease is the leading cause of dementia and among the top ten leading causes of death in high-income countries. Exponential advances in epidemiology, genetics, diagnostic imaging and fluid biomarkers, treatment, and prevention in the last decade reinforce the notion that we are entering a new era in the clinical management of Alzheimer's disease. However, far from triumphalism, this momentum should be accelerated to achieve the goals of preventing Alzheimer's disease and arresting its progression. In this Seminar, we summarise this progress and highlight unmet needs and areas of research priority.
BACKGROUND:There remains little evidence on whether opioid agonist treatment (OAT) is associated with a reduction in all-cause mortality in the context of widespread buprenorphine use. We aimed to study the risk of mortality in French primary care patients using OAT according to time on or off OAT treatment. METHODS:In this population-based, retrospective cohort study, we used data from the French National Health Data System (Système National de Données de Santé; SNDS). We included patients aged 15 years and older who began OAT between Jan 1, 2010, and Dec 31, 2022, and had at least two consecutively dispensed opioid agonists. Covariate data were also retrieved from the SNDS and included age, sex, deprivation index, medical comorbidities, psychiatric disorders, and concurrent medication. The primary endpoint was all-cause mortality by 1 year; all-cause mortality by 2, 5, and 7 years and specific mortality were the secondary endpoints. Multivariate Cox models accounting for time-dependent exposure (on OAT vs off OAT) were used to assess the association between OAT and mortality. FINDINGS:We included 175 191 individuals using OAT, of whom 131 444 (75·0%) were male and 43 747 (25·0%) were female. The median follow-up period was 3320 days (IQR 2055-4328). At inclusion, most patients had received buprenorphine (114 247 [65·2%]) or buprenorphine-naloxone (5895 [3·4%]). OAT use was associated with a lower risk of all-cause death at 1 year (adjusted hazard ratio [HR] 0·41 [95% CI 0·37-0·44]; absolute risk difference per 1000 person-years: 21·45 [19·32-23·58]), and this association persisted at 2 years (adjusted HR 0·36 [95% CI 0·34-0·39]), 5 years (0·36 [0·34-0·38]), and 7 years (0·40 [0·37-0·42]). OAT was also associated with lower cause-specific mortality, including injury or poisoning, drug-related deaths, accidental overdoses, infectious causes, and suicide, with similar patterns over time. The association was especially marked for buprenorphine, which had a 6-fold lower risk of all-cause death at 1 year (adjusted HR 0·16 [0·14-0·18]). INTERPRETATION:In this large, nationwide cohort of incident participants using OAT, we identified a large decrease in the risk of all-cause death associated with treatment. The association was especially marked for buprenorphine, even if this might result from indication bias. FUNDING:EPI-PHARE Scientific Interest Group in Epidemiology of Health Products from the French National Agency for the Safety of Medicines and Health Products and the French National Health Insurance.
