| 1. |
- Andersen, Zorana J., et al.
(författare)
-
Long-term exposure to ambient air pollution and incidence of postmenopausal breast cancer in 15 European cohorts within the ESCAPE project
- 2017
-
Ingår i: Journal of Environmental Health Perspectives. - Research triangle park : US department of health. - 0091-6765 .- 1552-9924. ; 125:10
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Epidemiological evidence on the association between ambient air pollution and breast cancer risk is inconsistent.OBJECTIVE: We examined the association between long-term exposure to ambient air pollution and incidence of postmenopausal breast cancer in European women.METHODS: In 15 cohorts from nine European countries, individual estimates of air pollution levels at the residence were estimated by standardized land-use regression models developed within the European Study of Cohorts for Air Pollution Effects (ESCAPE) and Transport related Air Pollution and Health impacts – Integrated Methodologies for Assessing Particulate Matter (TRANSPHORM) projects: particulate matter (PM) ≤2.5μm, ≤10μm, and 2.5–10μm in diameter (PM2.5, PM10, and PMcoarse, respectively); PM2.5 absorbance; nitrogen oxides (NO2 and NOx); traffic intensity; and elemental composition of PM. We estimated cohort-specific associations between breast cancer and air pollutants using Cox regression models, adjusting for major lifestyle risk factors, and pooled cohort-specific estimates using random-effects meta-analyses.RESULTS: Of 74,750 postmenopausal women included in the study, 3,612 developed breast cancer during 991,353 person-years of follow-up. We found positive and statistically insignificant associations between breast cancer and PM2.5 {hazard ratio (HR)=1.08 [95% confidence interval (CI): 0.77, 1.51] per 5 μg/m(3)}, PM10 [1.07 (95% CI: 0.89, 1.30) per 10 μg/m(3)], PMcoarse[1.20 (95% CI: 0.96, 1.49 per 5 μg/m(3)], and NO(2) [1.02 (95% CI: 0.98, 1.07 per 10 μg/m(3)], and a statistically significant association with NOx [1.04 (95% CI: 1.00, 1.08) per 20 μg/m(3), p=0.04].CONCLUSIONS: We found suggestive evidence of an association between ambient air pollution and incidence of postmenopausal breast cancer in European women.
|
|
| 2. |
- Clerici, Francesca, et al.
(författare)
-
Does Vascular Burden Contribute to the Progression of Mild Cognitive Impairment to Dementia?
- 2012
-
Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 34:3-4, s. 235-243
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: To investigate the contribution of vascular risk factors (VRFs), vascular diseases (VDs) and white matter lesions (WMLs) to the progression of mild cognitive impairment (MCI) to dementia and Alzheimer’s disease (AD). Methods: Two hundred forty-five consecutive subjects with MCI (age 74.09 ± 6.92 years) were followed for an average of 2.4 years. The Hachinski Ischemic Score and the Framingham Stroke Risk Profile were used to summarize VRFs and VDs. WMLs were graded using the Age-Related White Matter Changes Scale. Results: One hundred twenty-nine (52.6%) out of 245 subjects at risk converted to dementia, including 87 cases of AD. When hypertension occurred in MCI with deep WMLs, a 1.8-fold increased risk of dementia was observed (95% CI = 1.0–3.4). When deep WMLs occurred in MCI with high scores (≥4) on the Hachinski scale, a 3.5-fold (95% CI = 1.6–7.4) and 3.8-fold (95% CI = 1.2–11.5) risk of progression to dementia and AD was observed, respectively. Analogously, the joint effect of WMLs and high scores (≥14) on the Framingham scale nearly doubled the risk of dementia (hazard ratio = 1.9, 95% CI = 1.1–3.3). Conclusions: Accelerated progression of MCI to dementia and AD is to be expected when VRFs and VDs occur together with WMLs.
|
|
| 3. |
- Escott-Price, Valentina, et al.
(författare)
-
Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
- 2014
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e94661-
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-8)) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
|
|
| 4. |
- Jones, Lesley, et al.
(författare)
-
Convergent genetic and expression data implicate immunity in Alzheimer's disease
- 2015
-
Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:6, s. 658-671
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis. Methods: The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results: ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 X 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 X 10(-11)), cholesterol transport (P = 2.96 X 10(-9)), and proteasome-ubiquitin activity (P = 1.34 X 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05). Conclusions: The immime response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics.
|
|
| 5. |
- Pérez, Laura M., et al.
(författare)
-
Glutathione Serum Levels and Rate of Multimorbidity Development in Older Adults
- 2020
-
Ingår i: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press (OUP). - 1079-5006 .- 1758-535X. ; 75:6, s. 1089-1094
-
Tidskriftsartikel (refereegranskat)abstract
- We aimed to investigate the association between baseline levels of total serum glutathione (tGSH) and rate of chronic disease accumulation over time. The study population (n = 2,596) was derived from a population-based longitudinal study on >= 60-year-olds living in Stockholm. Participants were clinically assessed at baseline, 3- and 6-year follow-ups. Multimorbidity was measured as the number of chronic conditions from a previously built list of 60 diseases. Linear mixed models were applied to analyze the association between baseline tGSH levels and the rate of multimorbidity development over 6 years. We found that at baseline, participants with >= 4 diseases had lower tGSH levels than participants with no chronic conditions (3.3 vs 3.6 mu mol/L; p < .001). At follow-up, baseline levels of tGSH were inversely associated with the rate of multimorbidity development (beta * time: -0.044, p < .001) after adjusting for age, sex, education, levels of serum creatinine, C-reactive protein, albumin, body mass index, smoking, and time of dropout or death. In conclusion, serum levels of tGSH are inversely associated with multimorbidity development; the association exists above and beyond the link between tGSH and specific chronic conditions. Our findings support the hypothesis that tGSH is a biomarker of multisystem dysregulation that eventually leads to multimorbidity.
|
|
| 6. |
- Agüero-Torres, Hedda, et al.
(författare)
-
Institutionalization in the elderly : The role of chronic diseases and dementia. Cross-sectional and longitudinal data from a population-based study
- 2001
-
Ingår i: Journal of Clinical Epidemiology. - : Elsevier. - 0895-4356 .- 1878-5921. ; 54:8, s. 795-801
-
Tidskriftsartikel (refereegranskat)abstract
- A population-based study of 1810 persons, aged 75+, was investigated to evaluate the role of dementia and other chronic diseases as determinants of institutionalization in the elderly. The study population was examined at baseline and after a 3-year interval. After adjustment for sociodemographic characteristics, functional dependence, dementia, cerebrovascular disease and hip fracture were associated with living in an institution at baseline. Additionally, functional dependence, hip fracture and dementia were also associated with moving to an institution during the 3-year follow-up. In a similar analysis, including only nondemented subjects, the Mini-Mental State Examination emerged as one of the strongest determinants. The population attributable risk percentage of institutionalization during the 3-year follow-up due to dementia was 61%. This study confirms that dementia and cognitive impairment are the main contributors to institutionalization in the elderly, independently of their sociodemographic status, social network, or functional status.
|
|
| 7. |
- 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.
|
|
| 8. |
- 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.
|
|
| 9. |
- Andersen, Zorana J., et al.
(författare)
-
Long-term Exposure to Ambient Air Pollution and Incidence of Brain Tumor : the European Study of Cohorts for Air Pollution Effects (ESCAPE)
- 2018
-
Ingår i: Neuro-Oncology. - : Oxford University Press. - 1522-8517 .- 1523-5866. ; 20:3, s. 420-432
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Epidemiological evidence on the association between ambient air pollution and brain tumor risk is sparse and inconsistent.Methods: In 12 cohorts from 6 European countries, individual estimates of annual mean air pollution levels at the baseline residence were estimated by standardized land-use regression models developed within the ESCAPE and TRANSPHORM projects: particulate matter (PM) ≤2.5, ≤10, and 2.5–10 μm in diameter (PM2.5, PM10, and PMcoarse), PM2.5 absorbance, nitrogen oxides (NO2 and NOx) and elemental composition of PM. We estimated cohort-specific associations of air pollutant concentrations and traffic intensity with total, malignant, and nonmalignant brain tumor, in separate Cox regression models, adjusting for risk factors, and pooled cohort-specific estimates using random-effects meta-analyses.Results: Of 282194 subjects from 12 cohorts, 466 developed malignant brain tumors during 12 years of follow-up. Six of the cohorts also had data on nonmalignant brain tumor, where among 106786 subjects, 366 developed brain tumor: 176 nonmalignant and 190 malignant. We found a positive, statistically nonsignificant association between malignant brain tumor and PM2.5 absorbance (hazard ratio and 95% CI: 1.67; 0.89–3.14 per 10–5/m3), and weak positive or null associations with the other pollutants. Hazard ratio for PM2.5 absorbance (1.01; 0.38–2.71 per 10–5/m3) and all other pollutants were lower for nonmalignant than for malignant brain tumors.Conclusion: We found suggestive evidence of an association between long-term exposure to PM2.5 absorbance indicating traffic-related air pollution and malignant brain tumors, and no association with overall or nonmalignant brain tumors.
|
|
| 10. |
- Angleman, Sara B., et al.
(författare)
-
Multidimensional Prognostic Index in Association with Future Mortality and Number of Hospital Days in a Population-Based Sample of Older Adults : Results of the EU Funded MPI_AGE Project
- 2015
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:7
-
Tidskriftsartikel (refereegranskat)abstract
- Background The Multidimensional Prognostic Index (MPI) has been found to predict mortality in patients with a variety of clinical conditions. We aimed to assess the association of the MPI with future mortality and number of in-hospital days for the first time in a population-based cohort. Methods The study population consisted of 2472 persons, aged 66-99 years, from the Swedish National Study on Aging and Care in Kungsholmen, Sweden, who underwent the baseline visit 2001-4, and were followed up >10 years for in-hospital days and >12 years for mortality. The MPI was a modified version of the original and aggregated seven domains (personal and instrumental activities of daily living, cognitive function, illness severity and comorbidity, number of medications, co-habitation status, and nutritional status). The MPI score was divided into risk groups: low, medium and high. Number of in-hospital days (within 1, 3 and 10 years) and mortality data were derived from official registries. All analyses were age-stratified (sexagenarians, septuagenarians, octogenarians, nonagenarians). Results During the follow-up 1331 persons (53.8%) died. Laplace regression models, suggested that median survival in medium risk groups varied by age from 2.2-3.6 years earlier than for those in the corresponding low risk groups (p = 0.002-p<0.001), and median survival in high risk groups varied by age from 3.8-9.0 years earlier than for corresponding low risk groups (p<0.001). For nonagenarians, the median age at death was 3.8 years earlier in the high risk group than for the low risk group (p<0.001). The mean number of in-hospital days increased significantly with higher MPI risk score within 1 and 3 years for people of each age group. Conclusion For the first time, the effectiveness of MPI has been verified in a population-based cohort. Higher MPI risk scores associated with more days in hospital and with fewer years of survival, across a broad and stratified age range.
|
|
