| 1. |
- Kivimäki, Mika, et al.
(författare)
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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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Ingår i: The BMJ. - : BMJ Publishing Group Ltd. - 1756-1833. ; 374
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Tidskriftsartikel (refereegranskat)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.
(författare)
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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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Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 18:12
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Tidskriftsartikel (refereegranskat)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.
(författare)
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Association of Alcohol-Induced Loss of Consciousness and Overall Alcohol Consumption With Risk for Dementia
- 2020
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Ingår i: JAMA Network Open. - : American Medical Association. - 2574-3805. ; 3:9
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Tidskriftsartikel (refereegranskat)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.
(författare)
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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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Ingår i: International Journal of Obesity. - : Nature Publishing Group. - 0307-0565 .- 1476-5497. ; 44:6, s. 1368-1375
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Tidskriftsartikel (refereegranskat)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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