Association of Alcohol-Induced Loss of Consciousness and Overall Alcohol Consumption With Risk for Dementia

This cohort study examines the association of overall consumption of alcohol and resultant loss of consciousness with risk for dementia. Question Are alcohol-induced loss of consciousness and heavy weekly alcohol consumption associated with increased risk of future dementia? Findings In this multicohort study of 131x202f;415 adults, a 1.2-fold excess risk of dementia was associated with heavy vs moderate alcohol consumption. Those who reported having lost consciousness due to alcohol consumption, regardless of their overall weekly consumption, had a 2-fold increased risk of dementia compared with people who had not lost consciousness and were moderate drinkers. Meaning The findings of this study suggest that alcohol-induced loss of consciousness is a long-term risk factor for dementia among both heavy and moderate drinkers. Importance Evidence on alcohol consumption as a risk factor for dementia usually relates to overall consumption. The role of alcohol-induced loss of consciousness is uncertain. Objective To examine the risk of future dementia associated with overall alcohol consumption and alcohol-induced loss of consciousness in a population of current drinkers. Design, Setting, and Participants Seven cohort studies from the UK, France, Sweden, and Finland (IPD-Work consortium) including 131x202f;415 participants were examined. At baseline (1986-2012), participants were aged 18 to 77 years, reported alcohol consumption, and were free of diagnosed dementia. Dementia was examined during a mean follow-up of 14.4 years (range, 12.3-30.1). Data analysis was conducted from November 17, 2019, to May 23, 2020. Exposures Self-reported overall consumption and loss of consciousness due to alcohol consumption were assessed at baseline. Two thresholds were used to define heavy overall consumption: greater than 14 units (U) (UK definition) and greater than 21 U (US definition) per week. Main Outcomes and Measures Dementia and alcohol-related disorders to 2016 were ascertained from linked electronic health records. Results Of the 131x202f;415 participants (mean [SD] age, 43.0 [10.4] years; 80x202f;344 [61.1%] women), 1081 individuals (0.8%) developed dementia. After adjustment for potential confounders, the hazard ratio (HR) was 1.16 (95% CI, 0.98-1.37) for consuming greater than 14 vs 1 to 14 U of alcohol per week and 1.22 (95% CI, 1.01-1.48) for greater than 21 vs 1 to 21 U/wk. Of the 96x202f;591 participants with data on loss of consciousness, 10x202f;004 individuals (10.4%) reported having lost consciousness due to alcohol consumption in the past 12 months. The association between loss of consciousness and dementia was observed in men (HR, 2.86; 95% CI, 1.77-4.63) and women (HR, 2.09; 95% CI, 1.34-3.25) during the first 10 years of follow-up (HR, 2.72; 95% CI, 1.78-4.15), after excluding the first 10 years of follow-up (HR, 1.86; 95% CI, 1.16-2.99), and for early-onset (= 65 y: HR, 2.25; 95% CI, 1.38-3.66) dementia, Alzheimer disease (HR, 1.98; 95% CI, 1.28-3.07), and dementia with features of atherosclerotic cardiovascular disease (HR, 4.18; 95% CI, 1.86-9.37). The association with dementia was not explained by 14 other alcohol-related conditions. With moderate drinkers (1-14 U/wk) who had not lost consciousness as the reference group, the HR for dementia was twice as high in participants who reported having lost consciousness, whether their mean weekly consumption was moderate (HR, 2.19; 95% CI, 1.42-3.37) or heavy (HR, 2.36; 95% CI, 1.57-3.54). Conclusions and Relevance The findings of this study suggest that alcohol-induced loss of consciousness, irrespective of overall alcohol consumption, is associated with a subsequent increase in the risk of dementia.Peer reviewe

Cognitive stimulation in the workplace, plasma proteins, and risk of dementia : three analyses of population cohort studies

OBJECTIVES To examine the association between cognitively stimulating work and subsequent risk of dementia and to identify protein pathways for this association. DESIGN Multicohort study with three sets of analyses. SETTING United Kingdom, Europe, and the United States. PARTICIPANTS Three associations were examined: cognitive stimulation and dementia risk in 107 896 participants from seven population based prospective cohort studies from the IPD-Work consortium (individual participant data meta-analysis in working populations); cognitive stimulation and proteins in a random sample of 2261 participants from one cohort study; and proteins and dementia risk in 13 656 participants from two cohort studies. MAIN OUTCOME MEASURES Cognitive stimulation was measured at baseline using standard questionnaire instruments on active versus passive jobs and at baseline and over time using a job exposure matrix indicator. 4953 proteins in plasma samples were scanned. Follow-up of incident dementia varied between 13.7 to 30.1 years depending on the cohort. People with dementia were identified through linked electronic health records and repeated clinical examinations. RESULTS During 1.8 million person years at risk, 1143 people with dementia were recorded. The risk of dementia was found to be lower for participants with high compared with low cognitive stimulation at work (crude incidence of dementia per 10 000 person years 4.8 in the high stimulation group and 7.3 in the low stimulation group, age and sex adjusted hazard ratio 0.77, 95% confidence interval 0.65 to 0.92, heterogeneity in cohort specific estimates I2=0%, P=0.99). This association was robust to additional adjustment for education, risk factors for dementia in adulthood (smoking, heavy alcohol consumption, physical inactivity, job strain, obesity, hypertension, and prevalent diabetes at baseline), and cardiometabolic diseases (diabetes, coronary heart disease, stroke) before dementia diagnosis (fully adjusted hazard ratio 0.82, 95% confidence interval 0.68 to 0.98). The risk of dementia was also observed during the first 10 years of follow-up (hazard ratio 0.60, 95% confidence interval 0.37 to 0.95) and from year 10 onwards (0.79, 0.66 to 0.95) and replicated using a repeated job exposure matrix indicator of cognitive stimulation (hazard ratio per 1 standard deviation increase 0.77, 95% confidence interval 0.69 to 0.86). In analysis controlling for multiple testing, higher cognitive stimulation at work was associated with lower levels of proteins that inhibit central nervous system axonogenesis and synaptogenesis: slit homologue 2 (SLIT2, fully adjusted r3 -0.34, P(0.001), carbohydrate sulfotransferase 12 (CHSTC, fully adjusted r3 -0.33, P(0.001), and peptidyl-glycine alpha-amidating monooxygenase (AMD, fully adjusted r3 -0.32, P(0.001). These proteins were associated with increased dementia risk, with the fully adjusted hazard ratio per 1 SD being 1.16 (95% confidence interval 1.05 to 1.28) for SLIT2, 1.13 (1.00 to 1.27) for CHSTC, and 1.04 (0.97 to 1.13) for AMD. CONCLUSIONS The risk of dementia in old age was found to be lower in people with cognitively stimulating jobs than in those with non-stimulating jobs. The findings thatPeer reviewe

Long working hours, socioeconomic status, and the risk of incident type 2 diabetes : a meta-analysis of published and unpublished data from 222 120 individuals

Background Working long hours might have adverse health effects, but whether this is true for all socioeconomic status groups is unclear. In this meta-analysis stratified by socioeconomic status, we investigated the role of long working hours as a risk factor for type 2 diabetes. Methods We identified four published studies through a systematic literature search of PubMed and Embase up to April 30, 2014. Study inclusion criteria were English-language publication; prospective design (cohort study); investigation of the effect of working hours or overtime work; incident diabetes as an outcome; and relative risks, odds ratios, or hazard ratios (HRs) with 95% CIs, or sufficient information to calculate these estimates. Additionally, we used unpublished individual-level data from 19 cohort studies from the Individual-Participant-Data Meta-analysis in Working-Populations Consortium and international open-access data archives. Effect estimates from published and unpublished data from 222 120 men and women from the USA, Europe, Japan, and Australia were pooled with random-effects meta-analysis. Findings During 1.7 million person-years at risk, 4963 individuals developed diabetes (incidence 29 per 10 000 person-years). The minimally adjusted summary risk ratio for long (>= 55 h per week) compared with standard working hours (35-40 h) was 1.07 (95% CI 0.89-1.27, difference in incidence three cases per 10 000 person-years) with significant heterogeneity in study-specific estimates (I-2 = 53%, p = 0.0016). In an analysis stratified by socioeconomic status, the association between long working hours and diabetes was evident in the low socioeconomic status group (risk ratio 1.29, 95% CI 1.06-1.57, difference in incidence 13 per 10 000 person-years, I-2 = 0%, p = 0.4662), but was null in the high socioeconomic status group (1. 00, 95% CI 0.80-1.25, incidence diff erence zero per 10 000 person-years, I-2 = 15%, p = 0.2464). The association in the low socioeconomic status group was robust to adjustment for age, sex, obesity, and physical activity, and remained after exclusion of shift workers. Interpretation In this meta-analysis, the link between longer working hours and type 2 diabetes was apparent only in individuals in the low socioeconomic status groups. Copyright (C) Kivimaki et al. Open Access article distributed under the terms of CC BY.Peer reviewe

A genomic view on syntrophic versus non-syntrophic lifestyle in anaerobic fatty acid degrading communities

In sulfate-reducing and methanogenic environments complex biopolymers are hydrolyzed and degraded by fermentative micro-organisms that produce hydrogen, carbon dioxide and short chain fatty acids. Degradation of short chain fatty acids can be coupled to methanogenesis or to sulfate-reduction. Here we study from a genome perspective why some of these micro-organisms are able to grow in syntrophy with methanogens and others are not. Bacterial strains were selected based on genome availability and upon their ability to grow on short chain fatty acids alone or in syntrophic association with methanogens. Systematic functional domain profiling allowed us to shed light on this fundamental and ecologically important question. Extra-cytoplasmic formate dehydrogenases (InterPro domain number; IPR006443), including their maturation protein FdhE (IPR024064 and IPR006452) is a typical difference between syntrophic and non-syntrophic butyrate and propionate degraders. Furthermore, two domains with a currently unknown function seem to be associated with the ability of syntrophic growth. One is putatively involved in capsule or biofilm production (IPR019079) and a second in cell division, shape-determination or sporulation (IPR018365). The sulfate-reducing bacteria Desulfobacterium autotrophicum HRM2, Desulfomonile tiedjei and Desulfosporosinus meridiei were never tested for syntrophic growth, but all crucial domains were found in their genomes, which suggests their possible ability to grow in syntrophic association with methanogens. In addition, profiling domains involved in electron transfer mechanisms revealed the important role of the Rnf-complex and the formate transporter in syntrophy, and indicate that DUF224 may have a role in electron transfer in bacteria other than Syntrophomonas wolfei as well. This article was invited for a Special Issue entitled: 18th European Bioenergetic Conference.This research was financed by grants of BE-Basic (project 7.2.3.), the Technology Foundation, the Applied Science Division (STW) (project 11603) and the Divisions CW and ALW (projects 700.55.343 and 819.02.014) of the Netherlands Science Foundation (NWO) and ERC (project 323009). Furthermore, this work was carried out on the Dutch national e-infrastructure with the support of

systematic review and meta-analysis of published studies and unpublished individual participant data

Objective To quantify the association between long working hours and alcohol use. Design Systematic review and meta-analysis of published studies and unpublished individual participant data. Data sources A systematic search of PubMed and Embase databases in April 2014 for published studies, supplemented with manual searches. Unpublished individual participant data were obtained from 27 additional studies. Review methods The search strategy was designed to retrieve cross sectional and prospective studies of the association between long working hours and alcohol use. Summary estimates were obtained with random effects meta-analysis. Sources of heterogeneity were examined with meta-regression. Results Cross sectional analysis was based on 61 studies representing 333 693 participants from 14 countries. Prospective analysis was based on 20 studies representing 100 602 participants from nine countries. The pooled maximum adjusted odds ratio for the association between long working hours and alcohol use was 1.11 (95% confidence interval 1.05 to 1.18) in the cross sectional analysis of published and unpublished data. Odds ratio of new onset risky alcohol use was 1.12 (1.04 to 1.20) in the analysis of prospective published and unpublished data. In the 18 studies with individual participant data it was possible to assess the European Union Working Time Directive, which recommends an upper limit of 48 hours a week. Odds ratios of new onset risky alcohol use for those working 49-54 hours and ≥55 hours a week were 1.13 (1.02 to 1.26; adjusted difference in incidence 0.8 percentage points) and 1.12 (1.01 to 1.25; adjusted difference in incidence 0.7 percentage points), respectively, compared with working standard 35-40 hours (incidence of new onset risky alcohol use 6.2%). There was no difference in these associations between men and women or by age or socioeconomic groups, geographical regions, sample type (population based v occupational cohort), prevalence of risky alcohol use in the cohort, or sample attrition rate. Conclusions Individuals whose working hours exceed standard recommendations are more likely to increase their alcohol use to levels that pose a health risk

Long working hours and risk of coronary heart disease and stroke : a systematic review and meta-analysis of published and unpublished data for 603 838 individuals

Background Long working hours might increase the risk of cardiovascular disease, but prospective evidence is scarce, imprecise, and mostly limited to coronary heart disease. We aimed to assess long working hours as a risk factor for incident coronary heart disease and stroke. Methods We identified published studies through a systematic review of PubMed and Embase from inception to Aug 20, 2014. We obtained unpublished data for 20 cohort studies from the Individual-Participant-Data Meta-analysis in Working Populations (IPD-Work) Consortium and open-access data archives. We used cumulative random-effects meta-analysis to combine effect estimates from published and unpublished data. Findings We included 25 studies from 24 cohorts in Europe, the USA, and Australia. The meta-analysis of coronary heart disease comprised data for 603 838 men and women who were free from coronary heart disease at baseline; the meta-analysis of stroke comprised data for 528 908 men and women who were free from stroke at baseline. Follow-up for coronary heart disease was 5.1 million person-years (mean 8.5 years), in which 4768 events were recorded, and for stroke was 3.8 million person-years (mean 7.2 years), in which 1722 events were recorded. In cumulative meta-analysis adjusted for age, sex, and socioeconomic status, compared with standard hours (35-40 h per week), working long hours (>= 55 h per week) was associated with an increase in risk of incident coronary heart disease (relative risk [RR] 1.13, 95% CI 1.02-1.26; p=0.02) and incident stroke (1.33, 1.11-1.61; p=0.002). The excess risk of stroke remained unchanged in analyses that addressed reverse causation, multivariable adjustments for other risk factors, and different methods of stroke ascertainment (range of RR estimates 1.30-1.42). We recorded a dose-response association for stroke, with RR estimates of 1.10 (95% CI 0.94-1.28; p=0.24) for 41-48 working hours, 1.27 (1.03-1.56; p=0.03) for 49-54 working hours, and 1.33 (1.11-1.61; p=0.002) for 55 working hours or more per week compared with standard working hours (p(trend) Interpretation Employees who work long hours have a higher risk of stroke than those working standard hours; the association with coronary heart disease is weaker. These findings suggest that more attention should be paid to the management of vascular risk factors in individuals who work long hours. Copyright (C) Kivimaki et al. Open Access article distributed under the terms of CC BY.Peer reviewe

Association of Alcohol-Induced Loss of Consciousness and Overall Alcohol Consumption With Risk for Dementia

This cohort study examines the association of overall consumption of alcohol and resultant loss of consciousness with risk for dementia.Question Are alcohol-induced loss of consciousness and heavy weekly alcohol consumption associated with increased risk of future dementia? Findings In this multicohort study of 131x202f;415 adults, a 1.2-fold excess risk of dementia was associated with heavy vs moderate alcohol consumption. Those who reported having lost consciousness due to alcohol consumption, regardless of their overall weekly consumption, had a 2-fold increased risk of dementia compared with people who had not lost consciousness and were moderate drinkers. Meaning The findings of this study suggest that alcohol-induced loss of consciousness is a long-term risk factor for dementia among both heavy and moderate drinkers.Importance Evidence on alcohol consumption as a risk factor for dementia usually relates to overall consumption. The role of alcohol-induced loss of consciousness is uncertain. Objective To examine the risk of future dementia associated with overall alcohol consumption and alcohol-induced loss of consciousness in a population of current drinkers. Design, Setting, and Participants Seven cohort studies from the UK, France, Sweden, and Finland (IPD-Work consortium) including 131x202f;415 participants were examined. At baseline (1986-2012), participants were aged 18 to 77 years, reported alcohol consumption, and were free of diagnosed dementia. Dementia was examined during a mean follow-up of 14.4 years (range, 12.3-30.1). Data analysis was conducted from November 17, 2019, to May 23, 2020. Exposures Self-reported overall consumption and loss of consciousness due to alcohol consumption were assessed at baseline. Two thresholds were used to define heavy overall consumption: greater than 14 units (U) (UK definition) and greater than 21 U (US definition) per week. Main Outcomes and Measures Dementia and alcohol-related disorders to 2016 were ascertained from linked electronic health records. Results Of the 131x202f;415 participants (mean [SD] age, 43.0 [10.4] years; 80x202f;344 [61.1%] women), 1081 individuals (0.8%) developed dementia. After adjustment for potential confounders, the hazard ratio (HR) was 1.16 (95% CI, 0.98-1.37) for consuming greater than 14 vs 1 to 14 U of alcohol per week and 1.22 (95% CI, 1.01-1.48) for greater than 21 vs 1 to 21 U/wk. Of the 96x202f;591 participants with data on loss of consciousness, 10x202f;004 individuals (10.4%) reported having lost consciousness due to alcohol consumption in the past 12 months. The association between loss of consciousness and dementia was observed in men (HR, 2.86; 95% CI, 1.77-4.63) and women (HR, 2.09; 95% CI, 1.34-3.25) during the first 10 years of follow-up (HR, 2.72; 95% CI, 1.78-4.15), after excluding the first 10 years of follow-up (HR, 1.86; 95% CI, 1.16-2.99), and for early-onset (= 65 y: HR, 2.25; 95% CI, 1.38-3.66) dementia, Alzheimer disease (HR, 1.98; 95% CI, 1.28-3.07), and dementia with features of atherosclerotic cardiovascular disease (HR, 4.18; 95% CI, 1.86-9.37). The association with dementia was not explained by 14 other alcohol-related conditions. With moderate drinkers (1-14 U/wk) who had not lost consciousness as the reference group, the HR for dementia was twice as high in participants who reported having lost consciousness, whether their mean weekly consumption was moderate (HR, 2.19; 95% CI, 1.42-3.37) or heavy (HR, 2.36; 95% CI, 1.57-3.54). Conclusions and Relevance The findings of this study suggest that alcohol-induced loss of consciousness, irrespective of overall alcohol consumption, is associated with a subsequent increase in the risk of dementia

Work stress and risk of death in men and women with and without cardiometabolic disease: a multicohort study

BackgroundAlthough some cardiovascular disease prevention guidelines suggest a need to manage work stress in patients with established cardiometabolic disease, the evidence base for this recommendation is weak. We sought to clarify the status of stress as a risk factor in cardiometabolic disease by investigating the associations between work stress and mortality in men and women with and without pre-existing cardiometabolic disease.MethodsIn this multicohort study, we used data from seven cohort studies in the IPD-Work consortium, initiated between 1985 and 2002 in Finland, France, Sweden, and the UK, to examine the association between work stress and mortality. Work stress was denoted as job strain or effort–reward imbalance at work. We extracted individual-level data on prevalent cardiometabolic diseases (coronary heart disease, stroke, or diabetes [without differentiation by diabetes type]) at baseline. Work stressors, socioeconomic status, and conventional and lifestyle risk factors (systolic and diastolic blood pressure, total cholesterol, smoking status, BMI, physical activity, and alcohol consumption) were also assessed at baseline. Mortality data, including date and cause of death, were obtained from national death registries. We used Cox proportional hazards regression to study the associations of work stressors with mortality in men and women with and without cardiometabolic disease.ResultsWe identified 102 633 individuals with 1 423 753 person-years at risk (mean follow-up 13·9 years [SD 3·9]), of whom 3441 had prevalent cardiometabolic disease at baseline and 3841 died during follow-up. In men with cardiometabolic disease, age-standardised mortality rates were substantially higher in people with job strain (149·8 per 10 000 person-years) than in those without (97·7 per 10 000 person-years; mortality difference 52·1 per 10 000 person-years; multivariable-adjusted hazard ratio [HR] 1·68, 95% CI 1·19–2·35). This mortality difference for job strain was almost as great as that for current smoking versus former smoking (78·1 per 10 000 person-years) and greater than those due to hypertension, high total cholesterol concentration, obesity, physical inactivity, and high alcohol consumption relative to the corresponding lower risk groups (mortality difference 5·9–44·0 per 10 000 person-years). Excess mortality associated with job strain was also noted in men with cardiometabolic disease who had achieved treatment targets, including groups with a healthy lifestyle (HR 2·01, 95% CI 1·18–3·43) and those with normal blood pressure and no dyslipidaemia (6·17, 1·74–21·9). In all women and in men without cardiometabolic disease, relative risk estimates for the work stress–mortality association were not significant, apart from effort–reward imbalance in men without cardiometabolic disease (mortality difference 6·6 per 10 000 person-years; multivariable-adjusted HR 1·22, 1·06–1·41).InterpretationIn men with cardiometabolic disease, the contribution of job strain to risk of death was clinically significant and independent of conventional risk factors and their treatment, and measured lifestyle factors. Standard care targeting conventional risk factors is therefore unlikely to mitigate the mortality risk associated with job strain in this population.FundingNordForsk, UK Medical Research Council, and Academy of Finland.<br /

Obesity and loss of disease-free years owing to major non-communicable diseases: a multicohort study

Background Obesity increases the risk of several chronic diseases, but the extent to which the obesity-related loss of disease-free years varies by lifestyle category and across socioeconomic groups is unclear. We estimated the number of years free from major non-communicable diseases in adults who are overweight and obese, compared with those who are normal weight.Methods We pooled individual-level data on body-mass index (BMI) and non-communicable diseases from men and women with no initial evidence of these diseases in European cohort studies from the Individual-Participant-Data Meta-Analysis in Working Populations consortium. BMI was assessed at baseline (1991-2008) and non-communicable diseases (incident type 2 diabetes, coronary heart disease, stroke, cancer, asthma, and chronic obstructive pulmonary disease) were ascertained via linkage to records from national health registries, repeated medical examinations, or self-report. Disease-free years from age 40 years to 75 years associated with underweight (BMI = 25 kg/m(2) to = 30 kg/m(2) to = 35 kg/m(2)) compared with normal weight (>= 18.5 kg/m(2) to <25 kg/m(2)) were estimated.Findings Of 137 503 participants from ten studies, we excluded 6973 owing to missing data and 10 349 with prevalent disease at baseline, resulting in an analytic sample of 120 181 participants. Of 47 127 men, 211 (0.4%) were underweight, 21 468 (45.6%) normal weight, 20 738 (44.0%) overweight, 3982 (8.4%) class I obese, and 728 (1.5%) class II-III obese. The corresponding numbers among the 73 054 women were 1493 (2.0%), 44 760 (61.3%), 19 553 (26.8%), 5670 (7.8%), and 1578 (2.2%), respectively. During 1 328 873 person-years at risk (mean follow-up 11.5 years [range 6.3-18.6]), 8159 men and 8100 women developed at least one non-communicable disease. Between 40 years and 75 years, the estimated number of disease-free years was 29.3 (95% CI 28.8-29.8) in normal-weight men and 29.4 (28.7-30.0) in normal-weight women. Compared with normal weight, the loss of disease-free years in men was 1.8 (95% CI -1.3 to 4.9) for underweight, 1.1 (0.7 to 1.5) for overweight, 3.9 (2.9 to 4.9) for class I obese, and 8.5 (7.1 to 9.8) for class II-III obese. The corresponding estimates for women were 0.0 (-1.4 to 1.4) for underweight, 1.1 (0.6 to 1.5) for overweight, 2.7 (1.5 to 3.9) for class I obese, and 7.3 (6.1 to 8.6) for class II-III obese. The loss of disease-free years associated with class II-III obesity varied between 7.1 and 10.0 years in subgroups of participants of different socioeconomic level, physical activity level, and smoking habit.Interpretation Mild obesity was associated with the loss of one in ten, and severe obesity the loss of one in four potential disease-free years during middle and later adulthood. This increasing loss of disease-free years as obesity becomes more severe occurred in both sexes, among smokers and non-smokers, the physically active and inactive, and across the socioeconomic hierarchy. Copyright (c) 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

Non-Standard Errors

In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty: Non-standard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for better reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants