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  • Almqvist, Catarina, et al. (författare)
  • LifeGene-a large prospective population-based study of global relevance
  • 2011
  • Ingår i: European Journal of Epidemiology. - Springer. - 0393-2990 .- 1573-7284. ; 26:1, s. 67-77
  • Tidskriftsartikel (refereegranskat)abstract
    • Studying gene-environment interactions requires that the amount and quality of the lifestyle data is comparable to what is available for the corresponding genomic data. Sweden has several crucial prerequisites for comprehensive longitudinal biomedical research, such as the personal identity number, the universally available national health care system, continuously updated population and health registries and a scientifically motivated population. LifeGene builds on these strengths to bridge the gap between basic research and clinical applications with particular attention to populations, through a unique design in a research-friendly setting. LifeGene is designed both as a prospective cohort study and an infrastructure with repeated contacts of study participants approximately every 5 years. Index persons aged 18-45 years old will be recruited and invited to include their household members (partner and any children). A comprehensive questionnaire addressing cutting-edge research questions will be administered through the web with short follow-ups annually. Biosamples and physical measurements will also be collected at baseline, and re-administered every 5 years thereafter. Event-based sampling will be a key feature of LifeGene. The household-based design will give the opportunity to involve young couples prior to and during pregnancy, allowing for the first study of children born into cohort with complete pre-and perinatal data from both the mother and father. Questions and sampling schemes will be tailored to the participants' age and life events. The target of LifeGene is to enrol 500,000 Swedes and follow them longitudinally for at least 20 years.
  • Altman, Daniel, et al. (författare)
  • The genetic and environmental contribution to the occurrence of bladder pain syndrome: an empirical approach in a nationwide population sample.
  • 2011
  • Ingår i: European urology. - 1873-7560. ; 59:2, s. 280-5
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The aetiology of bladder pain syndrome (BPS) remains poorly understood, and a number of pathogenic mechanisms have been proposed. The importance of genetic factors for BPS is receiving growing attention, but data so far are of a preliminary nature. OBJECTIVE: To empirically assess the genetic and environmental contribution to BPS in a population-based sample of twins. DESIGN, SETTING, AND PARTICIPANTS: The study included >25 000 twins born between 1959 and 1985. Individuals with BPS were identified using latent class cluster analysis (LCCA) based on self-reported symptoms from a nationwide screening for complex diseases in the Swedish Twin Registry. By comparing monozygotic and dizygotic twins, we estimated twin similarity and the relative proportions of phenotypic variance resulting from genetic and environmental factors. MEASUREMENTS: Twin similarity was measured. RESULTS AND LIMITATIONS: The LCCA yielded an overall BPS prevalence of 1.1% and 2.4% for males and females, respectively. In males, the contribution of genetic effects to BPS could not be assessed because of the small number of concordant twin pairs. In women, twin similarity estimates indicated a genetic component for the aetiology of BPS, but genetic factors contributed less than one-third of the total variation in susceptibility to BPS. Nonshared environmental factors accounted for more than two-thirds of the variance, whereas early nongenetic factors shared within the family were of little or no consequence to the risk of developing BPS later in life. Use of self-reported symptoms to define the disease phenotype is a limitation of the study. CONCLUSIONS: The influence of environmental factors in the development of BPS in women is substantial, whereas genetic influences are of only modest importance for the possibility of developing the disease.
  • Andel, Ross, et al. (författare)
  • Work-related exposure to extremely low-frequency magnetic fields and dementia: results from the population-based study of dementia in Swedish twins.
  • 2010
  • Ingår i: The journals of gerontology. Series A, Biological sciences and medical sciences. - 1758-535X. ; 65:11, s. 1220-7
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. We examined the association between extremely low-frequency magnetic fields (EMF) and the risk of dementia and Alzheimer’s disease using all 9,508 individuals from the Study of Dementia in Swedish Twins (HARMONY) with valid occupational and diagnostic data.Methods. Dementia diagnoses were based on telephone screening followed by in-person clinical workup. Main lifetime occupation was coded according to an established EMF exposure matrix. Covariates were age, gender, education, vascular risk factors, and complexity of work. Based on previous research, data were also analyzed separately for cases with disease onset by age 75 years versus later, men versus women, and those with manual versus nonmanual main occupation. We used generalized estimating equations with the entire sample (to adjust for the inclusion of complete twin pairs) and conditional logistic regression with complete twin pairs only.Results. Level of EMF exposure was not significantly associated with dementia or Alzheimer’s disease. However, in stratified analyses, medium and high levels of EMF exposure were associated with increased dementia risk compared with low level in cases with onset by age 75 years (odds ratio: 1.94, 95% confidence interval: 1.07–3.65 for medium, odds ratio: 2.01, 95% confidence interval: 1.10–3.65 for high) and in participants with manual occupations (odds ratio: 1.81, 95% confidence interval: 1.06–3.09 for medium, odds ratio: 1.75, 95% confidence interval: 1.00–3.05 for high). Results with 42 twin pairs discordant for dementia did not reach statistical significance.Conclusions. Occupational EMF exposure appears relevant primarily to dementia with an earlier onset and among former manual workers.
  • Andel, Ross, et al. (författare)
  • Work-Related Stress May Increase the Risk of Vascular Dementia
  • 2012
  • Ingår i: Journal of The American Geriatrics Society. - 0002-8614. ; 60:1, s. 60-67
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To examine job control, job demands, social support at work, and job strain (ratio of demands to control) in relation to risk of any dementia, Alzheimer's disease (AD), and vascular dementia (VaD). DESIGN: Cohort study. SETTING: The population-based Study of Dementia in Swedish Twins. PARTICIPANTS: Two hundred fifty-seven people with dementia (167 AD, 46 VaD) and 9,849 without. MEASUREMENTS: Dementia diagnoses were based on telephone screening for cognitive impairment followed by in-person clinical examination. An established job exposure matrix was matched to main occupation categories to measure work characteristics. RESULTS: In generalized estimating equations (adjusted for the inclusion of complete twin pairs), lower job control was associated with greater risk of any dementia (odds ratio (OR) = 1.17, 95% confidence interval (CI) = 1.04-1.31) and VaD specifically (OR = 1.39, 95% CI = 1.07-1.81). Lower social support at work was associated with greater risk of dementia (OR = 1.15, 95% CI = 1.03-1.28), AD (OR = 1.14, 95% CI = 1.00-1.31), and VaD (OR = 1.28, 95% CI = 1.02-1.60). Greater job strain was associated with greater risk of VaD only (OR = 1.28, 95% CI = 1.02-1.60), especially in combination with low social support (OR = 1.35, 95% CI = 1.11-1.64). Age, sex, and education were controlled for. Work complexity, manual work, and vascular disease did not explain the results. No differences in work-related stress scores were observed in the 54 twin pairs discordant for dementia, although only two pairs included a twin with VaD. CONCLUSION: Work-related stress, including low job control and low social support at work, may increase the risk of dementia, particularly VaD. Modification to work environment, including attention to social context and provision of meaningful roles for employees, may contribute to efforts to promote cognitive health.
  • Bennet, Anna M, et al. (författare)
  • Genetic association of sequence variants near AGER/NOTCH4 and dementia.
  • 2011
  • Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 24:3, s. 475-84
  • Tidskriftsartikel (refereegranskat)abstract
    • We performed a survey of sequence variation in a series of 20 genes involved in inflammation-related pathways for association with dementia risk in twin and unrelated case-control samples consisting in total of 1462 Swedish dementia casesand 1929 controls. For a total of 218 tested genetic markers, strong evidence was obtained implicating a region near AGER and NOTCH4 on chromosome 6p with replication across both samples and maximum combined significance at marker rs1800625 (OR = 1.37, 95% CI 1.19–1.56, p = 1.36×10(–6)). Imputation of the associated genomic interval provided an improved signal atrs8365, near the 3UTR of AGER (p = 7.34×10(–7)). The associated region extends 120 kb encompassing 11 candidate genes.While AGER encodes a key receptor for amyloid-? protein, an analysis of network context based upon genes now confirmed to contribute to dementia risk (A?PP, PSEN1, PSEN2, CR1, CLU, PICALM, and APOE) suggested strong functional coupling to NOTCH4, with no significant coupling to the remaining candidates. The implicated region occurs in the broad HLA locus on chromosome 6p, but associated markers were not in strong LD with known variants that regulate HLA gene function, suggesting that this may represent a signal distinct from immune-system pathways.
  • Brommelhoff, Jessica A, et al. (författare)
  • Depression as a risk factor or prodromal feature for dementia? Findings in a population-based sample of Swedish twins.
  • 2009
  • Ingår i: Psychology and aging. - 0882-7974. ; 24:2, s. 373-84
  • Tidskriftsartikel (refereegranskat)abstract
    • This study tested whether history of depression is associated with an increased likelihood of dementia, and whether a first depressive episode earlier in life is associated with increased dementia risk, or whether only depressive episodes close in time to dementia onset are related to dementia. Depression information came from national hospital discharge registries, medical history, and medical records. Dementia was diagnosed clinically. In case-control results, individuals with recent registry-identified depression were 3.9 times more likely than those with no registry-identified depression history to have dementia, whereas registry-identified depression earlier in life was not associated with dementia risk. Each 1-year increase in time between depression onset and dementia onset or equivalent age decreased the likelihood of dementia by 8.4%. In co-twin control analyses, twins with prior depression were 3.0 times more likely to have dementia than their nondepressed twin partners, with a similar age of depression gradient. These findings suggest that after partially controlling for genetic influences, late-life depression for many individuals may be a prodrome rather than a risk factor for dementia.
  • Dahl, Anna K, et al. (författare)
  • Agreement between self-reported and measured height, weight and body mass index in old age : a longitudinal study with 20 years of follow-up
  • 2010
  • Ingår i: Age and Ageing. - 0002-0729. ; 39:4, s. 445-451
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: self-reported body mass index (BMI) based on self-reported height and weight is a widely used measure of adiposity in epidemiological research. Knowledge about the accuracy of these measures in late life is scarce. OBJECTIVE: the study aimed to evaluate the accuracy and changes in accuracy of self-reported height, weight and BMI calculated from self-reported height and weight in late life. DESIGN: a longitudinal population-based study with five times of follow-up was conducted. Participants: seven hundred seventy-four community-living men and women, aged 40-88 at baseline (mean age 63.9), included in The Swedish Adoption/Twin Study of Aging. METHODS: participants self-reported their height and weight in a questionnaire, and height and weight were measured by experienced research nurses at an in-person testing five times during a 20-year period. BMI was calculated as weight (kilogramme)/height (metre)(2). RESULTS: latent growth curve modelling showed an increase in the mean difference between self-reported and measured values over time for height (0.038 cm/year) and BMI (0.016 kg/m(2)/year), but not for weight. CONCLUSIONS: there is a very small increase in the mean difference between self-reported and measured BMI with ageing, which probably would not affect the results when self-reported BMI is used as a continuous variable in longitudinal studies.
  • Dahl, Anna K., 1975-, et al. (författare)
  • Body mass index across midlife and cognitive change in late life
  • 2013
  • Ingår i: International Journal of Obesity. - 0307-0565. ; 37:2, s. 296-302
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: High midlife body mass index (BMI) has been linked to a greater risk of dementia in late life, but few have studied the effect of BMI across midlife on cognitive abilities and cognitive change in a dementia-free sample.Methods: We investigated the association between BMI, measured twice across midlife (mean age 40 and 61 years, respectively), and cognitive change in four domains across two decades in the Swedish Adoption/Twin Study of Aging.Results: Latent growth curve models fitted to data from 657 non-demented participants showed that persons who were overweight/obese in early midlife had significantly lower cognitive performance across domains in late life and significantly steeper decline in perceptual speed, adjusting for cardio-metabolic factors. Both underweight and overweight/obesity in late midlife were associated with lower cognitive abilities in late life. However, the association between underweight and low cognitive abilities did not remain significant when weight decline between early and late midlife was controlled for.Conclusion: There is a negative effect on cognitive abilities later in life related to being overweight/obese across midlife. Moreover, weight decline across midlife rather than low weight in late midlife per se was associated with low cognitive abilities. Weight patterns across midlife may be prodromal markers of late life cognitive health.
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