| 1. |
- Middeldorp, Christel M., et al.
(författare)
-
The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia : design, results and future prospects
- 2019
-
Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 34:3, s. 279-300
-
Tidskriftsartikel (refereegranskat)abstract
- The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
|
|
| 2. |
- Gielen, Marij, et al.
(författare)
-
Body mass index is negatively associated with telomere length : A collaborative cross-sectional meta-analysis of 87 observational studies
- 2018
-
Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165. ; 108:3, s. 453-475
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Even before the onset of age-related diseases, obesity might be a contributing factor to the cumulative burden of oxidative stress and chronic inflammation throughout the life course. Obesity may therefore contribute to accelerated shortening of telomeres. Consequently, obese persons are more likely to have shorter telomeres, but the association between body mass index (BMI) and leukocyte telomere length (TL) might differ across the life span and between ethnicities and sexes. Objective: A collaborative cross-sectionalmeta-analysis of observational studies was conducted to investigate the associations between BMI and TL across the life span. Design: Eighty-seven distinct study samples were included in the meta-analysis capturing data from 146,114 individuals. Studyspecific age- and sex-adjusted regression coefficients were combined by using a random-effects model in which absolute [base pairs (bp)] and relative telomere to single-copy gene ratio (T/S ratio) TLs were regressed against BMI. Stratified analysis was performed by 3 age categories ("young": 18-60 y; "middle": 61-75 y; and "old": >75 y), sex, and ethnicity. Results: Each unit increase in BMI corresponded to a-3.99 bp (95% CI: -5.17, -2.81 bp) difference in TL in the total pooled sample; among young adults, each unit increase in BMI corresponded to a -7.67 bp (95% CI:-10.03,-5.31 bp) difference. Each unit increase in BMI corresponded to a -1.58 × 10-3 unit T/S ratio (0.16% decrease; 95% CI: -2.14 × 10-3, -1.01 × 10-3) difference in ageand sex-adjusted relative TL in the total pooled sample; among young adults, each unit increase in BMI corresponded to a -2.58 × 10-3 unit T/S ratio (0.26% decrease; 95% CI: -3.92 × 10-3, -1.25 × 10-3). The associations were predominantly for the white pooled population. No sex differences were observed. Conclusions: A higher BMI is associated with shorter telomeres, especially in younger individuals. The presently observed difference is not negligible. Meta-analyses of longitudinal studies evaluating change in body weight alongside change in TL arewarranted.
|
|
| 3. |
- Holme, Ingar, et al.
(författare)
-
Congestive heart failure is associated with lipoprotein components in statin-treated patients with coronary heart disease Insights from the Incremental Decrease in End points Through Aggressive Lipid Lowering Trial (IDEAL)
- 2009
-
Ingår i: ATHEROSCLEROSIS. - : Elsevier BV. - 0021-9150. ; 205:2, s. 522-527
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Very few, if any, studies have assessed the ability of apolipoproteins to predict new-onset of congestive heart failure (HF) in statin-treated patients with coronary heart disease (CHD). Aims: To employ the Incremental Decrease in End points Through Aggressive Lipid Lowering Trial (IDEAL) study database to assess the association of on-treatment lipoprotein components with prediction of HF events and to compare their predictive value with that of established risk factors such as hypertension and diabetes. Methods: We used Cox regression models to study the relationships between on-treatment levels of apolipoproteins A1 and B to subsequent HE Chi square information value from the log likelihood was used to compare the predictive value of lipoprotein components with established risk factors of HF. Findings: In the IDEAL study, on-treatment apolipoproteins proved to be associated with the occurrence of new-onset HE Variables related to low-density lipoprotein cholesterol (LDL-C) carried less predictive information than those related to high-density lipoprotein cholesterol (HDL-C), and apoA-1 was the single variable most strongly associated with HF. LDL-C was less predictive than both non-HDL-C (total cholesterol minus HDL-C) and apoB. The ratio of apoB to apoA-1 was most strongly related to HF after adjustment for potential confounders, among which diabetes had a stronger correlation with HF than did hypertension. ApoB/apoA-1 carried approximately 2.2 times more of the statistical information value than that of diabetes. Calculation of the net reclassification improvement index revealed that about 3.7% of the patients had to be reclassified into more correct categories of risk once apoB/apoA-1 was added to the adjustment factors. The reduction in risk by intensive lipid-lowering treatment as compared to usual-dose simvastatin was well predicted by the difference in apoB/apoA-1 on-treatment levels. Interpretation: The on-treatment ratio of apoB/apoA-1 was the strongest predictor of HF in CHD patients of both IDEAL treatment arms combined, mostly driven by the strong association with apoA-1, whereas LDL-C and non-HDL-C were less able to predict HF outcome. The predictive information value contained within apoB/apoA-1 was about 2.2 times more than that of diabetes. Between-treatment group differences in HF were to a significant extent explained by on-treatment differences in apoB/apoA-1, mostly through the changes in apoB. We argue therefore, on-treatment lipoprotein components contribute to the overall future risk of HF in statin-treated patients with CHD.
|
|
| 4. |
- Itzhaki, Ruth F., et al.
(författare)
-
Microbes and Alzheimer's disease
- 2017
-
Ingår i: Handbook of infection and Alzheimer's disease. - : IOS Press. - 9781614997054 - 9781614997061 ; , s. 3-8
-
Bokkapitel (refereegranskat)
|
|
| 5. |
- Janssen, Niels, et al.
(författare)
-
Association Between Cognition, Health Related Quality of Life, and Costs in a Population at Risk for Cognitive Decline
- 2022
-
Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 89:2, s. 623-632
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The association between health-related quality of life (HRQoL) and care costs in people at risk for cognitive decline is not well understood. Studying this association could reveal the potential benefits of increasing HRQoL and reducing care costs by improving cognition. Objective: In this exploratory data analysis we investigated the association between cognition, HRQoL utilities and costs in a well-functioning population at risk for cognitive decline. Methods: An exploratory data analysis was conducted using longitudinal 2-year data from the FINGER study (n= 1,120). A change score analysis was applied using HRQoL utilities and total medical care costs as outcome. HRQoL utilities were derived from the Short Form Health Survey-36 (SF-36). Total care costs comprised visits to a general practitioner, medical specialist, nurse, and days at hospital. Analyses were adjusted for activities of daily living (ADL) and depressive symptoms. Results: Although univariable analysis showed an association between cognition and HRQoL utilities, multivariable analysis showed no association between cognition, HRQoL utilities and total care costs. A one-unit increase in ADL limitations was associated with a -0.006 (p <0 .001) decrease in HRQoL utilities and a one-unit increase in depressive symptoms was associated with a -0.004 (p < 0.001) decrease in HRQoL utilities. Conclusion: The level of cognition in people at-risk for cognitive decline does not seem to be associated with HRQoL utilities. Future research should examine the level at which cognitive decline starts to affect HRQoL and care costs. Ideally, this would be done by means of cross-validation in populations with various stages of cognitive functioning and decline.
|
|
| 6. |
- Kivimäki, Mika, et al.
(författare)
-
Association of Alcohol-Induced Loss of Consciousness and Overall Alcohol Consumption With Risk for Dementia
- 2020
-
Ingår i: JAMA Network Open. - : American Medical Association. - 2574-3805. ; 3:9
-
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.
|
|
| 7. |
- Kivimäki, Mika, et al.
(författare)
-
Body-mass index and risk of obesity-related complex multimorbidity : an observational multicohort study
- 2022
-
Ingår i: The Lancet Diabetes and Endocrinology. - : Elsevier. - 2213-8587 .- 2213-8595. ; 10:4, s. 253-263
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The accumulation of disparate diseases in complex multimorbidity makes prevention difficult if each disease is targeted separately. We aimed to examine obesity as a shared risk factor for common diseases, determine associations between obesity-related diseases, and examine the role of obesity in the development of complex multimorbidity (four or more comorbid diseases). Methods: We did an observational study and used pooled prospective data from two Finnish cohort studies (the Health and Social Support Study and the Finnish Public Sector Study) comprising 114 657 adults aged 16–78 years at study entry (1998–2013). A cohort of 499 357 adults (aged 38–73 years at study entry; 2006–10) from the UK Biobank provided replication in an independent population. BMI and clinical characteristics were assessed at baseline. BMIs were categorised as obesity (≥30·0 kg/m2), overweight (25·0–29·9 kg/m2), healthy weight (18·5–24·9 kg/m2), and underweight (<18·5 kg/m2). Via linkage to national health records, participants were followed-up for death and diseases diagnosed according to the International Classification of Diseases 10th Revision (ICD-10). Hazard ratios (HRs) with 95% CIs and population attributable fractions (PAFs) for associations between BMI and multimorbidity were calculated. Findings: Mean follow-up duration was 12·1 years (SD 3·8) in the Finnish cohorts and 11·8 years (1·7) in the UK Biobank cohort. Obesity was associated with 21 non-overlapping cardiometabolic, digestive, respiratory, neurological, musculoskeletal, and infectious diseases after Bonferroni multiple testing adjustment and ignoring HRs of less than 1·50. Compared with healthy weight, the confounder-adjusted HR for obesity was 2·83 (95% CI 2·74–2·93; PAF 19·9% [95% CI 19·3–20·5]) for developing at least one obesity-related disease, 5·17 (4·84–5·53; 34·4% [33·2–35·5]) for two diseases, and 12·39 (9·26–16·58; 55·2% [50·9–57·5]) for complex multimorbidity. The proportion of participants of healthy weight with complex multimorbidity by age 75 years was observed by age 55 years in participants with obesity, and degree of obesity was associated with complex multimorbidity in a dose–response relationship. Compared with obesity, the association between overweight and complex multimorbidity was more modest (HR 2·67, 95% CI 1·94–3·68; PAF 13·3% [95% CI 9·6–16·3]). The same pattern of results was observed in the UK Biobank cohort. Interpretation: Obesity is associated with diverse, increasing disease burdens, and might represent an important target for multimorbidity prevention that avoids the complexities of multitarget preventive regimens. Funding: Wellcome Trust, Medical Research Council, National Institute on Aging.
|
|
| 8. |
- Kivimäki, Mika, et al.
(författare)
-
Physical inactivity, cardiometabolic disease, and risk of dementia : an individual-participant meta-analysis
- 2019
-
Ingår i: The BMJ. - ENGLAND : BMJ Publishing Group Ltd. - 1756-1833 .- 0959-8138. ; 365
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 9. |
- Kivimäki, Mika, et al.
(författare)
-
Work stress and risk of death in men and women with and without cardiometabolic disease : a multicohort study
- 2018
-
Ingår i: The Lancet Diabetes and Endocrinology. - : Elsevier. - 2213-8587 .- 2213-8595. ; 6:9, s. 705-713
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 10. |
- Kivipelto, Miia, et al.
(författare)
-
The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) : Study design and progress
- 2013
-
Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 9:6, s. 657-665
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) is a multi-center, randomized, controlled trial ongoing in Finland. Materials: Participants (1200 individuals at risk of cognitive decline) are recruited from previous population-based non-intervention studies. Inclusion criteria are CAIDE Dementia Risk Score >= 6 and cognitive performance at the mean level or slightly lower than expected for age (but not substantial impairment) assessed with the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological battery. The 2-year multidomain intervention consists of: nutritional guidance; exercise; cognitive training and social activity; and management of metabolic and vascular risk factors. Persons in the control group receive regular health advice. The primary outcome is cognitive performance as measured by the modified Neuropsychological Test Battery, Stroop test, and Trail Making Test. Main secondary outcomes are: dementia (after extended follow-up); disability; depressive symptoms; vascular risk factors and outcomes; quality of life; utilization of health resources; and neuroimaging measures. Results: Screening began in September 2009 and was completed in December 2011. All 1200 persons are enrolled and the intervention is ongoing as planned. Baseline clinical characteristics indicate that several vascular risk factors and unhealthy lifestyle related factors are present, creating a window of opportunity for prevention. The intervention will be completed during 2014. Conclusions: The FINGER is at the forefront of international collaborative efforts to solve the clinical and public health problems of early identification of individuals at increased risk of late-life cognitive impairment, and of developing intervention strategies to prevent or delay the onset of cognitive impairment and dementia.
|
|
