| 1. |
- Kivimäki, Mika, et al.
(author)
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Cognitive stimulation in the workplace, plasma proteins, and risk of dementia : three analyses of population cohort studies
- 2021
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In: The BMJ. - : BMJ Publishing Group Ltd. - 1756-1833. ; 374
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Journal article (peer-reviewed)abstract
- 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 β -0.34, P<0.001), carbohydrate sulfotransferase 12 (CHSTC, fully adjusted β -0.33, P<0.001), and peptidyl-glycine α-amidating monooxygenase (AMD, fully adjusted β -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 that cognitive stimulation is associated with lower levels of plasma proteins that potentially inhibit axonogenesis and synaptogenesis and increase the risk of dementia might provide clues to underlying biological mechanisms.
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| 2. |
- Walldius, Goran, et al.
(author)
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Long-term risk of a major cardiovascular event by apoB, apoA-1, and the apoB/apoA-1 ratio-Experience from the Swedish AMORIS cohort : A cohort study
- 2021
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In: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 18:12
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Journal article (peer-reviewed)abstract
- Background Elevated apolipoprotein B (apoB) and elevated apoB/apoA-1 ratio increase the risk of myocardial infarction (MI) and stroke, whereas high apoA-1 is protective. We study how these apolipoproteins are associated with major adverse cardiovascular events (MACEs), whether apoA-1 contributes to this association, and whether abnormal values occur decades before such events develop. Methods and findings In the Swedish AMORIS (Apolipoprotein-related MOrtality RISk) cohort study, 137,100 men and women aged 25-84 years were followed an average 17.8 years. ApoB, apoA-1, and the apoB/apoA-1 ratio were analysed in relation to MACEs (non-fatal MI, stroke, and cardiovascular [CV] mortality), yielding 22,473 events. Hazard ratios (HRs) were estimated using Cox regression. Kaplan-Meier estimates were used to investigate the relationship of MACEs with increasing quintiles of the apoB/apoA-1 ratio in all age groups for both sexes. In nested case-control analyses, cases were randomly matched to age- and sex-matched controls, yielding population trajectories for apolipoproteins. Increased level of apoB and increased apoB/apoA-1 ratio were associated with risk of MACE and all clinical sub-components in both men and women across all ages (10th versus first decile in both sexes combined: HR 1.7 for MACE and 2.7 for non-fatal MI). Decreased values of apoA-1 potentiated the impact of apoB at all levels of apoB (on average across apoB range: 40% increase in HR for MACE and 72% increase in HR for non-fatal MI), indicating that the apoB/apoA-1 ratio covers a broader range of persons with dyslipidaemia at risk than apoB alone. In both men and women, MACEs occurred earlier on average for each increasing quintile of the apoB/apoA-1 ratio. Individuals with the highest levels of apoB/apoA-1 ratio experienced CV events on average several years earlier than those with lower ratios. Higher apoB/apoA-1 ratio in cases of MACE versus controls was seen already about 20 years before the event. A limitation of this study was that adjustment for tobacco smoking and hypertension was only possible in a small validation study. Conclusions An imbalance between apoB and apoA-1 resulting in an increased apoB/apoA-1 ratio is strongly associated with the outcome MACE and its sub-components, in both men and women of all ages. An increased apoB/apoA-1 ratio already 2 decades before events calls for early recognition and primary prevention. Simple evidence-based cut values should be considered in future cardiovascular guidelines.
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| 3. |
- Kivimäki, Mika, et al.
(author)
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Association of Alcohol-Induced Loss of Consciousness and Overall Alcohol Consumption With Risk for Dementia
- 2020
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In: JAMA Network Open. - : American Medical Association. - 2574-3805. ; 3:9
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Journal article (peer-reviewed)abstract
- 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 131 415 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 131 415 participants (mean [SD] age, 43.0 [10.4] years; 80 344 [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 96 591 participants with data on loss of consciousness, 10 004 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, 2.21; 95% CI, 1.46-3.34) and late-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.
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| 4. |
- Virtanen, Marianna, et al.
(author)
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Long working hours and change in body weight : analysis of individual-participant data from 19 cohort studies
- 2020
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In: International Journal of Obesity. - : Nature Publishing Group. - 0307-0565 .- 1476-5497. ; 44:6, s. 1368-1375
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Journal article (peer-reviewed)abstract
- Objective: To examine the relation between long working hours and change in body mass index (BMI). Methods: We performed random effects meta-analyses using individual-participant data from 19 cohort studies from Europe, US and Australia (n = 122,078), with a mean of 4.4-year follow-up. Working hours were measured at baseline and categorised as part time (<35 h/week), standard weekly hours (35–40 h, reference), 41–48 h, 49–54 h and ≥55 h/week (long working hours). There were four outcomes at follow-up: (1) overweight/obesity (BMI ≥ 25 kg/m2) or (2) overweight (BMI 25–29.9 kg/m2) among participants without overweight/obesity at baseline; (3) obesity (BMI ≥ 30 kg/m2) among participants with overweight at baseline, and (4) weight loss among participants with obesity at baseline. Results: Of the 61,143 participants without overweight/obesity at baseline, 20.2% had overweight/obesity at follow-up. Compared with standard weekly working hours, the age-, sex- and socioeconomic status-adjusted relative risk (RR) of overweight/obesity was 0.95 (95% CI 0.90–1.00) for part-time work, 1.07 (1.02–1.12) for 41–48 weekly working hours, 1.09 (1.03–1.16) for 49–54 h and 1.17 (1.08–1.27) for long working hours (P for trend <0.0001). The findings were similar after multivariable adjustment and in subgroup analyses. Long working hours were associated with an excess risk of shift from normal weight to overweight rather than from overweight to obesity. Long working hours were not associated with weight loss among participants with obesity. Conclusions: This analysis of large individual-participant data suggests a small excess risk of overweight among the healthy-weight people who work long hours.
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| 5. |
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| 6. |
- Kivimäki, Mika, et al.
(author)
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Physical inactivity, cardiometabolic disease, and risk of dementia : an individual-participant meta-analysis
- 2019
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In: The BMJ. - ENGLAND : BMJ Publishing Group Ltd. - 1756-1833 .- 0959-8138. ; 365
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Journal article (peer-reviewed)abstract
- OBJECTIVE To 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. DESIGN Meta-analysis of 19 prospective observational cohort studies. DATA SOURCES The 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 METHOD The 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. RESULTS Study 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). CONCLUSIONS In 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.
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| 7. |
- du Prel, Jean-Baptist, et al.
(author)
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Work overcommitment : Is it a trait or a state?
- 2018
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In: International Archives of Occupational and Environmental Health. - : Springer Science and Business Media LLC. - 0340-0131 .- 1432-1246. ; 91:1, s. 1-11
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Journal article (peer-reviewed)abstract
- Effort-reward imbalance (ERI) is a well-tested work-related stress model with three components, the two extrinsic components efforts and rewards and the one intrinsic component overcommitment. While an imbalance between efforts and rewards leads to strain reactions, work-related overcommitment (OC) has been described as a personal characteristic with a set of attitudes, behaviours, and emotions reflecting excessive striving combined with a strong desire for approval. However, the question whether OC is a personality trait or a response pattern sensitive to changes in the work context (state) is still open. 2940 Swedish industrial employees were included in this longitudinal analysis of the WOLF-Norrland data over 5 years. A change of OC index or its subscales were regressed against a change of freedom of choice at work, extra work, and ERI adjusted for age, sex, and education. While OC was insensitive to changes in freedom of choice at work and extra work, it was clearly associated with changes of work-related stress over time. Three of four OC subscales exhibited statistically significant associations with ERI. For the first time, we studied fundamental characteristics of OC as an independent personality variable (trait) or an outcome variable subject to changes in the work environment (state). The association between external ERI and OC over time supports our hypothesis of OC being a state. Further investigations are needed to establish OC as a trait or a state.
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| 8. |
- Kivimäki, Mika, et al.
(author)
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Body mass index and risk of dementia : Analysis of individual-level data from 1.3 million individuals
- 2018
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In: Alzheimer's & Dementia. - : Elsevier. - 1552-5260 .- 1552-5279. ; 14:5, s. 601-609
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Journal article (peer-reviewed)abstract
- Introduction: Higher midlife body mass index (BMI) is suggested to increase the risk of dementia, but weight loss during the preclinical dementia phase may mask such effects. Methods: We examined this hypothesis in 1,349,857 dementia-free participants from 39 cohort studies. BMI was assessed at baseline. Dementia was ascertained at follow-up using linkage to electronic health records (N = 6894). We assumed BMI is little affected by preclinical dementia when assessed decades before dementia onset and much affected when assessed nearer diagnosis. Results: Hazard ratios per 5-kg/m(2) increase in BMI for dementia were 0.71 (95% confidence interval = 0.66-0.77), 0.94 (0.89-0.99), and 1.16 (1.05-1.27) when BMI was assessed 10 years, 10-20 years, and >20 years before dementia diagnosis. Conclusions: The association between BMI and dementia is likely to be attributable to two different processes: a harmful effect of higher BMI, which is observable in long follow-up, and a reverse-causation effect that makes a higher BMI to appear protective when the follow-up is short. (C) 2017 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association.
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| 9. |
- Kivimäki, Mika, et al.
(author)
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Work stress and risk of death in men and women with and without cardiometabolic disease : a multicohort study
- 2018
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In: The Lancet Diabetes and Endocrinology. - : Elsevier. - 2213-8587 .- 2213-8595. ; 6:9, s. 705-713
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Journal article (peer-reviewed)abstract
- BACKGROUND: Although 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.METHODS: In 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.RESULTS: We 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).INTERPRETATION: In 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.FUNDING: NordForsk, UK Medical Research Council, and Academy of Finland.
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| 10. |
- Theorell, Töres, et al.
(author)
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Obesity and loss of disease-free years owing to major non-communicable diseases : a multicohort study
- 2018
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In: The Lancet Public Health. - : Elsevier Ltd. - 2468-2667. ; 3:10, s. e490-e497
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Journal article (peer-reviewed)abstract
- 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 <18·5 kg/m2), overweight (≥25 kg/m2 to <30 kg/m2), and obesity (class I [mild] ≥30 kg/m2 to <35 kg/m2; class II–III [severe] ≥35 kg/m2) compared with normal weight (≥18·5 kg/m2 to <25 kg/m2) 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. Funding: NordForsk, UK Medical Research Council, US National Institute on Aging, Academy of Finland, Helsinki Institute of Life Science, and Cancer Research UK.
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