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AbstractObjectiveTo examine whether physical inactivity is a risk factor for dementia, with attention to the role of cardiometabolic disease in this association and reverse causation bias that arises from changes in physical activity in the preclinical (prodromal) phase of dementia.DesignMeta-analysis of 19 prospective observational cohort studies.Data sourcesThe Individual-Participant-Data Meta-analysis in Working Populations Consortium, the Inter-University Consortium for Political and Social Research, and the UK Data Service, including a total of 19 of a potential 9741 studies.Review methodThe search strategy was designed to retrieve individual-participant data from prospective cohort studies. Exposure was physical inactivity; primary outcomes were incident all-cause dementia and Alzheimer’s disease; and the secondary outcome was incident cardiometabolic disease (that is, diabetes, coronary heart disease, and stroke). Summary estimates were obtained using random effects meta-analysis.ResultsStudy population included 404 840 people (mean age 45.5 years, 57.7% women) who were initially free of dementia, had a measurement of physical inactivity at study entry, and were linked to electronic health records. In 6.0 million person-years at risk, we recorded 2044 incident cases of all-cause dementia. In studies with data on dementia subtype, the number of incident cases of Alzheimer’s disease was 1602 in 5.2 million person-years. When measured <10 years before dementia diagnosis (that is, the preclinical stage of dementia), physical inactivity was associated with increased incidence of all-cause dementia (hazard ratio 1.40, 95% confidence interval 1.23 to 1.71) and Alzheimer’s disease (1.36, 1.12 to 1.65). When reverse causation was minimised by assessing physical activity ≥10 years before dementia onset, no difference in dementia risk between physically active and inactive participants was observed (hazard ratios 1.01 (0.89 to 1.14) and 0.96 (0.85 to 1.08) for the two outcomes). Physical inactivity was consistently associated with increased risk of incident diabetes (hazard ratio 1.42, 1.25 to 1.61), coronary heart disease (1.24, 1.13 to 1.36), and stroke (1.16, 1.05 to 1.27). Among people in whom cardiometabolic disease preceded dementia, physical inactivity was non-significantly associated with dementia (hazard ratio for physical activity assessed >10 before dementia onset 1.30, 0.79 to 2.14).ConclusionsIn analyses that addressed bias due to reverse causation, physical inactivity was not associated with all-cause dementia or Alzheimer’s disease, although an indication of excess dementia risk was observed in a subgroup of physically inactive individuals who developed cardiometabolic disease.

Black carbon (BC), a component of fine particulate matter [particles with an aerodynamic diameter ( )], may contribute to carcinogenic effects of air pollution. Until recently however, there has been little evidence to evaluate this hypothesis. This study aimed to estimate the associations between long-term exposure to BC and risk of cancer. This study was conducted within the French Gazel cohort of 20,625 subjects. We assessed exposure to BC by linking subjects' histories of residential addresses to a map of European black carbon levels in 2010 with back- and forward-extrapolation between 1989 and 2015. We used extended Cox models, with attained age as time-scale and time-varying cumulative exposure to BC, adjusted for relevant sociodemographic and lifestyle variables. To consider latency between exposure and cancer diagnosis, we implemented a 10-y lag, and as a sensitivity analysis, a lag of 2 y. To isolate the effect of BC from that of total , we regressed BC on and used the residuals as the exposure variable. During the 26-y follow-up period, there were 3,711 incident cancer cases (all sites combined) and 349 incident lung cancers. Median baseline exposure in 1989 was 2.65 [interquartile range (IQR): 2.23-3.33], which generally slightly decreased over time. Using 10 y as a lag-time in our models, the adjusted hazard ratio per each IQR increase of the natural log-transformed cumulative BC was 1.17 (95% confidence interval: 1.06, 1.29) for all-sites cancer combined and 1.31 (0.93, 1.83) for lung cancer. Associations with BC residuals were also positive for both outcomes. Using 2 y as a lag-time, the results were similar. Our findings for a cohort of French adults suggest that BC may partly explain the association between and lung cancer. Additional studies are needed to confirm our results and further disentangle the effects of BC, total , and other constituents. https://doi.org/10.1289/EHP8719.

Substance use is more prevalent among unemployed subjects compared to employed ones. However, quantifying the risk subsequent of job loss at short-term according to substance use remains underexplored as well as examining if this association persist across various sociodemographic and occupational positions previously linked to job loss. We examined this issue prospectively for alcohol, tobacco, cannabis use and their combination, among a large population-based sample of men and women, while taking into account age, gender, overall health status and depressive symptoms. From the French population-based CONSTANCES cohort, 18,879 working participants were included between 2012 and 2016. At baseline, alcohol use disorder risk according to the Alcohol Use Disorders Identification Test (mild, dangerous, problematic or dependence), tobacco (non-smoker, former smoker, 1-9, 10-19, >19 cigarettes/day) and cannabis use (never, not in past year, less than once a month, once a month or more) were assessed. Employment status at one-year (working versus not working) was the dependent variable. Logistic regressions provided Odds Ratios(OR(95%CI)) of job loss at one-year, adjusting for age, gender, self-reported health and depressive state (measured with the Center of Epidemiologic Studies Depression scale). Stratified analyses were performed for education, occupational grade, household income, job stress (measured with the Effort-Reward Imbalance), type of job contract, type of work time and history of unemployment. In sensitivity analyses, employment status over a three-year follow-up was used as dependent variable. Alcohol, tobacco and cannabis use were associated with job loss, from the second to the highest category: 1.46(95%CI:1.23-1.73) to 1.92(95%CI:1.34-2.75), 1.26(95%CI:1.09-1.46) to 1.78(95%CI:1.26-2.54) and 1.45(95%CI:1.27-1.66) to 2.68(95%CI:2.10-3.42), respectively, and with dose-dependent relationships (all p for trend <0.001). When introduced simultaneously, associations remained significant for the three substances without any between-substance interactions. Associations remained significant across almost all stratifications and over a three-year follow-up as well as after adjustment for all the sociodemographic and occupational factors. Alcohol, tobacco and cannabis use were independently associated with job loss at short-term, with dose-dependent relationships. This knowledge will help refining information and prevention strategies. Importantly, even moderate levels of alcohol, tobacco or cannabis use are associated with job loss at short-term and all sociodemographic and occupational positions are potentially concerned.

Besides the usual characterization of metabolic syndrome as a cluster of markers arbitrarily defined by thresholds, it is unclear to which extent these markers as continuous traits are correlated with each other in the general population. The present study aimed to explore these correlations across a wide array of biological, social and behavioral characteristics. The cross-sectional analyses were performed in a large population-based French cohort (CONSTANCES) of 159,476 adults in whom blood glucose, low-density lipoproteins (LDL) and high-density lipoproteins (HDL), triglycerides, body mass index, waist and hip circumferences, systolic and diastolic blood pressures were measured at the time of recruitment between 2012 and 2021. Correlations between each pair of continuous marker distributions were assessed by calculating raw and partial correlation coefficients (r). The same pattern of partial correlations is observed with little variation in all groups of sex, age, individual and parental histories of cardiovascular disease, diagnosis of metabolic syndrome, social position, work environment, lifetime unemployment exposure, smoking, non-moderate alcohol consumption, leisure-time physical inactivity and diet quality. This pattern is composed of strong and expected intercorrelations between systolic and diastolic blood pressures (r ranging from 0.62 to 0.74), between body mass index and waist (r from 0.50 to 0.63) and hip (r from 0.58 to 0.70) circumferences and between waist and hip circumferences (r from 0.07 to 0.19). It also includes intercorrelations of systolic blood pressure with waist (r from 0.10 to 0.21) and hip (r from -0.07 to -0.12) circumferences and with blood glucose (r from 0.09 to 0.15), those of triglycerides with blood glucose (r from 0.07 to 0.16), LDL (r from 0.24 to 0.33), HDL (r from -0.20 to -0.29) and waist circumference (r from 0.07 to 0.15), and finally those of waist and hip circumferences with blood glucose (r from 0.09 to 0.17 and from -0.08 to -0.13) and HDL (r from -0.12 to -0.24 and from 0.08 to 0.18). These results show that metabolic syndrome markers are correlated with each other whatever the biological, social or behavioral characteristics of individuals. They suggest that it makes sense to systematically consider these markers all together rather than separately in terms of etiology, prevention and treatment of metabolic diseases and cardiovascular risk in the general population.

Background Data are lacking regarding the prevalence of benzodiazepine long-term use in the general population. Our aim was to examine the prevalence of prescribed benzodiazepine long-term use (BLTU) according to sociodemographic and clinical factors in the French general population. Methods Data came from 4686 men and 4849 women included in 2015 in the French population-based CONSTANCES cohort. BLTU was examined using drug reimbursement administrative registries from 2009 to 2015. Analyses were weighted to provide results representative of the French general population covered by the general health insurance scheme. Weighted prevalence of BTLU and weighted Odds Ratios (OR) of having BTLU were computed with their 95% Confidence Interval (95% CI) according to age, education level, occupational status, occupational grade, household income, marital status, alcohol use disorder risk and depressive symptoms. All the analyses were stratified for gender. Results Weighted prevalence of BLTU were 2.8%(95% CI:2.3–3.4) and 3.8%(95% CI: 3.3–4.5) in men and women, respectively. Compared to men, women had an increased risk of having benzodiazepine long-term use with OR = 1.34(95% CI = 1.02–1.76). Aging, low education, not being at-work, low occupational grade, low income, being alone and depressive state were associated with increased risks of having BTLU. Conclusions BLTU is widespread in the French general population, however this issue may particularly concern vulnerable subgroups. These findings may help in raising attention on this public health burden as well as targeting specific at-risk subgroups in preventive intervention.

Governments need to increase the proportion of the population in work in most developed countries because of ageing populations. We investigated longitudinally how self-perceived health is affected by work and retirement in older workers. We examined trajectories of self-rated health in 14 714 employees (11 581 [79%] men) from the French national gas and electricity company, the GAZEL cohort, for up to 7 years before and 7 years after retirement, with yearly measurements from 1989 to 2007. We analysed data by use of repeated-measures logistic regression with generalised estimating equations. Overall, suboptimum health increased with age. However, between the year before retirement and the year after, the estimated prevalence of suboptimum health fell from 19·2% (95% CI 18·5–19·9) to 14·3% (13·7–14·9), corresponding to a gain in health of 8–10 years. We noted this retirement-related improvement in men (odds ratio 0·68, 95% CI 0·64–0·73) and women (0·74, 0·67–0·83), and across occupational grades (low 0·72, 0·63–0·82; high 0·70, 0·63–0·77), and it was maintained throughout the 7 years after retirement. A poor work environment and health complaints before retirement were associated with a steeper yearly increase in the prevalence of suboptimum health while still in work, and a greater retirement-related improvement; however, people with a combination of high occupational grade, low demands, and high satisfaction at work showed no such retirement-related improvement. These findings suggest that the burden of ill-health, in terms of perceived health problems, is substantially relieved by retirement for all groups of workers apart from those with ideal working conditions, and that working life for older workers needs to be redesigned to achieve higher labour-market participation. Swedish Council for Working Life and Social Research, Academy of Finland, INSERM (France), BUPA Foundation (UK), European Science Foundation, and Economic and Social Research Council (UK).

Background Lifetime unemployment exposure increases in a cumulative way the risk of chronic diseases and premature death but the linearity of these relationships is still unclear. Methods The analyses were performed using individual data from 114,307 participants aged 18 to 75 years who were followed for 7 years after inclusion in the large population-based French cohort CONSTANCES. Unemployment exposure was measured as the total number of unemployed quarters accumulated during the lifetime and categorized into quartiles (low, average, high, very high exposure) along with the group of participants who were never exposed to unemployment. The associations of lifetime unemployment exposure with cardiovascular disease, cancer and all-cause mortality rates during follow-up were assessed by using logistic regression models adjusted for major confounding factors. Adjusted logistic regression models were also used to examine the associations between lifetime unemployment exposure and the prevalence of bad working conditions at inclusion. Results The associations of lifetime unemployment exposure with cardiovascular disease and all-cause mortality rates appear to be J-shaped with lower rates observed in participants with a low unemployment exposure compared to those never exposed (odds ratios (95% CI) of 0.78 (0.63–0.96) and 0.81 (0.60–0.97) respectively). In contrast, an increase in cardiovascular disease and all-cause mortality rates is observed in participants with a high (1.40 (1.17–1.67) and 1.50 (1.18–1.89) respectively) and even more a very high unemployment exposure (1.64 (1.42–1.89) and 2.09 (1.74–2.50) respectively). These J-shaped associations are no longer significant when adjusted for working conditions at inclusion. The prevalence of bad working conditions at inclusion is also reduced in participants with a low unemployment exposure compared to those never exposed (0.83 (0.79–0.86)) while it is increased in participants with a high (1.61 (1.55–1.68)) and even more a very high unemployment exposure (2.12 (2.04–2.21)). Conclusions The non-linear relationships of lifetime unemployment exposure with cardiovascular disease and all-cause mortality rates may be related to the health benefits of having the occasional opportunity to leave jobs with bad working conditions over the life course.

Background The cardiovascular consequences of night work are increasingly well-known. Implementing effective preventive strategies, however, requires further investigation of the effects of exposure duration. This study sought to assess the cumulative dose–effect of night work exposure on the prevalence of cardiovascular risk factors among current and former night workers in France. Methods We used cross-sectional data from the CONSTANCES cohort to design analyses on 52,234 workers exposed or not exposed to night work during their working life. The cumulative duration of night work exposure was assessed among permanent, rotating and former night workers. BMI, blood pressure, lipids, glycaemia and SCORE2 were measured in health screening centres. Results Excess risks of moderate-high SCORE2 were observed for permanent (+ 43%), rotating (+ 72%) and former night workers (+ 101%). Among male permanent night workers, excess risks for obesity (+ 76%) and central obesity (64%) were recorded at five years of exposure and for T2DM (+ 119%) at 10 years of exposure. Male rotating night workers showed excess risks at five years of exposure for obesity/central obesity (about + 45%) and high triglyceridaemia (+ 52%). Female former night workers were at excess risk at five years of exposure for obesity/central obesity (about + 45%), HBP (+ 34%) and low-HDL-C (+ 35%). Conclusions The effects on cardiovascular risk factors varied according to the types of night work and within sex groups. Some effects were observed after five years of exposure. These results support the need for early and appropriate monitoring of cardiovascular risk factors among current and former night workers. Graphical Abstract

Differences in morbidity and mortality between socioeconomic groups constitute one of the most consistent findings of epidemiologic research. However, research on social inequalities in health has yet to provide a comprehensive understanding of the mechanisms underlying this association. In recent analysis, we showed health behaviours, assessed longitudinally over the follow-up, to explain a major proportion of the association of socioeconomic status (SES) with mortality in the British Whitehall II study. However, whether health behaviours are equally important mediators of the SES-mortality association in different cultural settings remains unknown. In the present paper, we examine this issue in Whitehall II and another prospective European cohort, the French GAZEL study. We included 9,771 participants from the Whitehall II study and 17,760 from the GAZEL study. Over the follow-up (mean 19.5 y in Whitehall II and 16.5 y in GAZEL), health behaviours (smoking, alcohol consumption, diet, and physical activity), were assessed longitudinally. Occupation (in the main analysis), education, and income (supplementary analysis) were the markers of SES. The socioeconomic gradient in smoking was greater (p<0.001) in Whitehall II (odds ratio [OR] = 3.68, 95% confidence interval [CI] 3.11-4.36) than in GAZEL (OR = 1.33, 95% CI 1.18-1.49); this was also true for unhealthy diet (OR = 7.42, 95% CI 5.19-10.60 in Whitehall II and OR = 1.31, 95% CI 1.15-1.49 in GAZEL, p<0.001). Socioeconomic differences in mortality were similar in the two cohorts, a hazard ratio of 1.62 (95% CI 1.28-2.05) in Whitehall II and 1.94 in GAZEL (95% CI 1.58-2.39) for lowest versus highest occupational position. Health behaviours attenuated the association of SES with mortality by 75% (95% CI 44%-149%) in Whitehall II but only by 19% (95% CI 13%-29%) in GAZEL. Analysis using education and income yielded similar results. Health behaviours were strong predictors of mortality in both cohorts but their association with SES was remarkably different. Thus, health behaviours are likely to be major contributors of socioeconomic differences in health only in contexts with a marked social characterisation of health behaviours. Please see later in the article for the Editors' Summary.

To study the association between occupational co-exposure to biomechanical risk factors, potentially neurotoxic chemicals and carpal tunnel syndrome (CTS) in a large cohort of French workers, using two methods to estimate chemical exposure: job-exposure matrices (JEM) and self-reported exposure. A randomly selected sample of adults were included between 2012 and 2018 in the French cohort CONSTANCES. Self-reported CTS was assessed using the first self-administered follow-up questionnaire, sent out approximately one year after baseline. Occupational exposure to biomechanical risk factors was assessed using self-administered questionnaire completed at inclusion. Lifetime occupational exposure to chemicals was assessed using two different methods: with JEMs and with a self-administered questionnaire completed at inclusion. Multivariate logistic regression models were used to evaluate the association between co-exposure to biomechanical risk factors and chemicals and CTS, adjusted for personal and medical factors and stratified by gender. For the analysis using JEM assessment, 35,941 workers (16,920 men and 19,021 women) were included: 261 men (1.5%) and 469 women (2.5%) declared having CTS at follow-up. There was an association between CTS and the co-exposure group: OR=2.37 [1.60-3.44] in men and OR=2.09 [1.55-2.77] in women, compared to the non-exposed group. For the self-reported chemicals analysis, 42,168 workers (20,877 men and 21,291 women) were included: 338 men (1.6%) and 532 women (2.5%) declared having CTS at follow-up. There was an association between CTS and the co-exposure group: OR=3.07 [2.28-4.08] in men and OR=2.68 [1.91-3.66] in women, compared to the non-exposed group. The study showed an association between self- reported CTS and co-exposure to biomechanical risk factors and chemicals. This finding should be confirmed using more objective case definition of CTS, e.g. carpal tunnel release surgery.