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Sökning: LAR1:gu > Pedersen Nancy L.

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1.
  • 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. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 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.
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  • 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. - : Oxford University Press (OUP). - 1758-535X .- 1079-5006. ; 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.
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4.
  • Andel, Ross, et al. (författare)
  • Work-Related Stress May Increase the Risk of Vascular Dementia
  • 2012
  • Ingår i: Journal of The American Geriatrics Society. - : Wiley. - 0002-8614 .- 1532-5415. ; 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.
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5.
  • 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-β protein, an analysis of network context based upon genes now confirmed to contribute to dementia risk (AβPP, 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.
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6.
  • Bennet, Anna M, et al. (författare)
  • Pleiotropy in the Presence of Allelic Heterogeneity: Alternative Genetic Models for the Influence of APOE on Serum LDL, CSF Amyloid-β42, and Dementia.
  • 2010
  • Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 22:1, s. 129-134
  • Tidskriftsartikel (refereegranskat)abstract
    • The two genetic polymorphisms, rs7412 and rs429358, that collectively form the ε2, ε3, and ε4 alleles of apolipoprotein E (APOE) are among the most widely studied sequence variants in the genome. The predominant model for testing APOE involves the haplotype combinations of ε2, ε3, and ε4 and has been basis of associations with dementia, atherosclerosis, and serum lipid levels. Here, we demonstrate the functional independence of these two component sites, with rs7412 contributing to the majority of variance in serum LDL (p=10-20), whereas rs429358 alone influences variance in CSF amyloid-β42 (Aβ42) (p=10-17). This latter relationship is also reflected in the association of APOE with dementia, where rs429358 strongly influences disease (p=10-67), but rs7412 does not. Models based upon ε2, ε3, and ε4 explained less variance for both dementia risk and CSF Aβ42 than did rs429358 alone. When adjusted for CSF Aβ42, the association of rs429358 with dementia is greatly reduced but remains significant indicating that APOE polymorphism influences disease by additional mechanisms distinct from Aβ42 metabolism. We reach four principal conclusion from this study: 1) rs429358 alone is responsible for the association of APOE with dementia; 2) The association of APOE with dementia is substantially mediated by its effect on CNS Aβ42 levels; 3) The association of APOE with dementia is not mediated by its impact on peripheral lipid metabolism; and 4) The dichotomy of effects of rs429358 and rs7412 represents one of the best examples of genetic pleiotropy for complex traits known and illustrates the importance of allelic heterogeneity in APOE.
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8.
  • 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. - : American Psychological Association (APA). - 0882-7974 .- 1939-1498. ; 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.
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9.
  • Dahl, Anna, et al. (författare)
  • Being overweight in midlife is associated with lower cognitive ability and steeper cognitive decline in late life.
  • 2010
  • Ingår i: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press (OUP). - 1758-535X .- 1079-5006. ; 65:1, s. 57-62
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Although an increasing body of evidence links being overweight in midlife with an increased risk for dementia in late life, no studies have examined the association between being overweight in midlife and cognitive ability in late life. Our aim was to examine the association between being overweight in midlife as measured by body mass index (BMI) and cognitive ability assessed over time. METHODS: Participants in the Swedish Adoption/Twin Study Aging were derived from a population-based sample. The participants completed baseline surveys in 1963 or 1973 (mean age 41.6 years, range 25-63 years). The surveys included questions about height, weight, diseases, and lifestyle factors. Beginning in 1986, the same individuals were assessed on neuropsychological tests every 3 years (except in 1995) until 2002. During the study period, 781 individuals who were 50 years and older (60% women) had at least one complete neuropsychological assessment. A composite score of general cognitive ability was derived from the cognitive test battery for each measurement occasion. RESULTS: Latent growth curve models adjusted for twinness showed that persons with higher midlife BMI scores had significantly lower general cognitive ability and significantly steeper longitudinal decline than their thinner counterparts. The association did not change substantially when persons who developed dementia during the study period were excluded from the analysis. CONCLUSIONS: Higher midlife BMI scores precede lower general cognitive ability and steeper cognitive decline in both men and women. The association does not seem to be mediated by an increased risk for dementia.
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10.
  • Dahl, Anna, et al. (författare)
  • Body mass index across midlife and cognitive change in late life
  • 2013
  • Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 37
  • 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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