1. |
- Andersen, Zorana J., et al.
(author)
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Long-term exposure to ambient air pollution and incidence of postmenopausal breast cancer in 15 European cohorts within the ESCAPE project
- 2017
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In: Journal of Environmental Health Perspectives. - Research triangle park : US department of health. - 0091-6765 .- 1552-9924. ; 125:10
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Journal article (peer-reviewed)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.
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2. |
- Clerici, Francesca, et al.
(author)
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Does Vascular Burden Contribute to the Progression of Mild Cognitive Impairment to Dementia?
- 2012
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In: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 34:3-4, s. 235-243
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Journal article (peer-reviewed)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.
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3. |
- Escott-Price, Valentina, et al.
(author)
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Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
- 2014
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e94661-
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Journal article (peer-reviewed)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.
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4. |
- Jones, Lesley, et al.
(author)
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Convergent genetic and expression data implicate immunity in Alzheimer's disease
- 2015
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In: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:6, s. 658-671
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Journal article (peer-reviewed)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.
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5. |
- Pérez, Laura M., et al.
(author)
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Glutathione Serum Levels and Rate of Multimorbidity Development in Older Adults
- 2020
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In: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press (OUP). - 1079-5006 .- 1758-535X. ; 75:6, s. 1089-1094
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Journal article (peer-reviewed)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.
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6. |
- Abbadi, Ahmad, et al.
(author)
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Validation of the Health Assessment Tool (HAT) based on four aging cohorts from the Swedish National study on Aging and Care
- 2024
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In: BMC Medicine. - : BioMed Central (BMC). - 1741-7015. ; 22:1
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Journal article (peer-reviewed)abstract
- Background: As global aging accelerates, routinely assessing the functional status and morbidity burden of older patients becomes paramount. The aim of this study is to assess the validity of the comprehensive clinical and functional Health Assessment Tool (HAT) based on four cohorts of older adults (60 + years) from the Swedish National study on Aging and Care (SNAC) spanning urban, suburban, and rural areas.Methods: The HAT integrates five health indicators (gait speed, global cognition, number of chronic diseases, and basic and instrumental activities of daily living), providing an individual-level score between 0 and 10. The tool was constructed using nominal response models, first separately for each cohort and then in a harmonized dataset. Outcomes included all-cause mortality over a maximum follow-up of 16 years and unplanned hospital admissions over a maximum of 3 years of follow-up. The predictive capacity was assessed through the area under the curve (AUC) using logistic regressions. For time to death, Cox regressions were performed, and Harrell’s C-indices were reported. Results from the four cohorts were pooled using individual participant data meta-analysis and compared with those from the harmonized dataset.Results: The HAT demonstrated high predictive capacity across all cohorts as well as in the harmonized dataset. In the harmonized dataset, the AUC was 0.84 (95% CI 0.81–0.87) for 1-year mortality, 0.81 (95% CI 0.80–0.83) for 3-year mortality, 0.80 (95% CI 0.79–0.82) for 5-year mortality, 0.69 (95% CI 0.67–0.70) for 1-year unplanned admissions, and 0.69 (95% CI 0.68–0.70) for 3-year unplanned admissions. The Harrell’s C for time-to-death throughout 16 years of follow-up was 0.75 (95% CI 0.74–0.75).Conclusions: The HAT is a highly predictive, clinically intuitive, and externally valid instrument with potential for better addressing older adults’ health needs and optimizing risk stratification at the population level. © The Author(s) 2024.
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7. |
- Agüero-Torres, Hedda, et al.
(author)
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Institutionalization in the elderly : The role of chronic diseases and dementia. Cross-sectional and longitudinal data from a population-based study
- 2001
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In: Journal of Clinical Epidemiology. - : Elsevier. - 0895-4356 .- 1878-5921. ; 54:8, s. 795-801
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Journal article (peer-reviewed)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.
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8. |
- Andel, Ross, et al.
(author)
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Work-related exposure to extremely low-frequency magnetic fields and dementia: results from the population-based study of dementia in Swedish twins.
- 2010
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In: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press (OUP). - 1758-535X .- 1079-5006. ; 65:11, s. 1220-7
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Journal article (peer-reviewed)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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9. |
- Andel, Ross, et al.
(author)
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Work-Related Stress May Increase the Risk of Vascular Dementia
- 2012
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In: Journal of The American Geriatrics Society. - : Wiley. - 0002-8614 .- 1532-5415. ; 60:1, s. 60-67
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Journal article (peer-reviewed)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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10. |
- Andersen, Zorana J., et al.
(author)
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Long-term Exposure to Ambient Air Pollution and Incidence of Brain Tumor : the European Study of Cohorts for Air Pollution Effects (ESCAPE)
- 2018
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In: Neuro-Oncology. - : Oxford University Press. - 1522-8517 .- 1523-5866. ; 20:3, s. 420-432
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Journal article (peer-reviewed)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.
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11. |
- Angleman, Sara B., et al.
(author)
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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
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:7
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Journal article (peer-reviewed)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.
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12. |
- Angleman, Sara B., et al.
(author)
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Temporal Trends of Functional Dependence and Survival Among Older Adults From 1991 to 2010 in Sweden : Toward a Healthier Aging
- 2015
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In: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press (OUP). - 1079-5006 .- 1758-535X. ; 70:6, s. 746-752
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Journal article (peer-reviewed)abstract
- Background. Declines in functional dependence among older adults were observed before the 1990s, but there is uncertainty about subsequent trends. Our study aimed to verify the temporal trends in disability during 1991-2010 in an older Swedish population and to estimate the associated changes in survival. Methods. Functional status in octogenarians and nonagenarians was assessed at seven occasions with intervals of 2-3 years. Sample size varied at each assessment with an average of 646 (range 212-1096). Disability was defined as difficulty in one or more of personal activities of daily living. We compared prevalence and incidence, as well as mortality, and survival associated with disability over the 20-year period. Results. Sex-standardized prevalence of disability remained steady over time with a tendency toward a gradual decline, and a statistically significant decrease was present among nonagenarians. Sex-standardized cumulative incidence also remained steady. The proportion of people with prevalent disability who died <3 years remained stable, as did the survival time of people with incident disability. In contrast, among nondisabled persons, 3-year mortality decreased significantly, and for octogenarians median survival time was 1.3 years longer at the more recent assessment than a decade earlier. Conclusions. Both prevalence and incidence of disability remained stable over the last two decades in this urban Swedish population, with a trend toward a slow decline. Mortality remained steady among disabled persons but decreased among persons without disability, suggesting that increased life expectancy during the last two decades may be essentially driven by longer lives of functionally independent people.
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13. |
- Anstey, Kaarin J., et al.
(author)
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A Self-Report Risk Index to Predict Occurrence of Dementia in Three Independent Cohorts of Older Adults : The ANU-ADRI
- 2014
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:1, s. e86141-
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Journal article (peer-reviewed)abstract
- Background and Aims: The Australian National University AD Risk Index (ANU-ADRI, http://anuadri.anu.edu.au) is a self-report risk index developed using an evidence-based medicine approach to measure risk of Alzheimer's disease (AD). We aimed to evaluate the extent to which the ANU-ADRI can predict the risk of AD in older adults and to compare the ANU-ADRI to the dementia risk index developed from the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study for middle-aged cohorts. Methods: This study included three validation cohorts, i.e., the Rush Memory and Aging Study (MAP) (n = 903, age >= 53 years), the Kungsholmen Project (KP) (n = 905, age >= 75 years), and the Cardiovascular Health Cognition Study (CVHS) (n = 2496, age >= 65 years) that were each followed for dementia. Baseline data were collected on exposure to the 15 risk factors included in the ANU-ADRI of which MAP had 10, KP had 8 and CVHS had 9. Risk scores and C-statistics were computed for individual participants for the ANU-ADRI and the CAIDE index. Results: For the ANU-ADRI using available data, the MAP study c-statistic was 0.637 (95% CI 0.596-0.678), for the KP study it was 0.740 (0.712-0.768) and for the CVHS it was 0.733 (0.691-0.776) for predicting AD. When a common set of risk and protective factors were used c-statistics were 0.689 (95% CI 0.650-0.727), 0.666 (0.628-0.704) and 0.734 (0.707-0.761) for MAP, KP and CVHS respectively. Results for CAIDE ranged from c-statistics of 0.488 (0.427-0.554) to 0.595 (0.565-0.625). Conclusion: A composite risk score derived from the ANU-ADRI weights including 8-10 risk or protective factors is a valid, self-report tool to identify those at risk of AD and dementia. The accuracy can be further improved in studies including more risk factors and younger cohorts with long-term follow-up.
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14. |
- Atti, Anna Rita, et al.
(author)
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Cognitive Impairment after Age 60 : clinical and Social Correlates in the "Faenza Project"
- 2010
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In: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 21:4, s. 1325-1334
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Journal article (peer-reviewed)abstract
- A total of 7,389 dementia-free elderly (60–102 years old) enrolled in the "Faenza Project" (Northern Italy) were clinically evaluated by nurses and physicians with the aim of detecting the independent and combined association of medical and social factors with cognitive status. Cognitive Impairment No Dementia (CIND) was defined for MMSE scores ⩽ 2 standard deviations than the age- and education-corrected mean score obtained by the non-demented persons of the Faenza cohort. Logistic Regression analysis was used to estimate Odds Ratios and 95% Confidence Intervals (OR, 95%CI) for CIND. The diagnostic procedure identified 402 (5.4%) CIND cases. Diabetes (OR, 95%CI=1.6, 1.2–2.2), stroke (OR, 95%CI=1.9, 1.4–2.6), and depressive symptoms (OR, 95%CI=1.9, 1.4–2.7) emerged as the most relevant medical comorbidities of CIND. Low education (OR, 95%CI=1.8, 1.1–2.9), low Socio Economic Status (SES) (OR, 95%CI=1.5, 1.1–2.1), and unmarried status (OR, 95%CI=1.7, 1.2–2.5) were associated with CIND. Medical and social factors were independently related to CIND occurrence. In comparison to subjects without any of the above mentioned conditions, subjects with one medical and one social factor had an OR, 95%CI for CIND equal to 6.0, 2.9–12.4. The strength of the association increased when more of those conditions occurred in combination, suggesting a synergistic effect. Despite some methodological limitations, data from this cross-sectional population-based Italian study show that low education, low SES, unmarried status together with diabetes, stroke, and depressive symptoms are related to cognitive impairment in the general population. The interaction of medical and social factors further increases the probability of CIND.
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15. |
- Beelen, Rob, et al.
(author)
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Effects of long-term exposure to air pollution on natural-cause mortality : an analysis of 22 European cohorts within the multicentre ESCAPE project
- 2014
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In: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 383:9919, s. 785-795
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Journal article (peer-reviewed)abstract
- Background Few studies on long-term exposure to air pollution and mortality have been reported from Europe. Within the multicentre European Study of Cohorts for Air Pollution Effects (ESCAPE), we aimed to investigate the association between natural-cause mortality and long-term exposure to several air pollutants. Methods We used data from 22 European cohort studies, which created a total study population of 367 251 participants. All cohorts were general population samples, although some were restricted to one sex only. With a strictly standardised protocol, we assessed residential exposure to air pollutants as annual average concentrations of particulate matter (PM) with diameters of less than 2.5 mu m (PM2.5), less than 10 mu m (PM10), and between 10 mu m and 2.5 mu m (PMcoarse), PM2.5 absorbance, and annual average concentrations of nitrogen oxides (NO2 and NOx), with land use regression models. We also investigated two traffic intensity variables-traffic intensity on the nearest road (vehicles per day) and total traffic load on all major roads within a 100 m buff er. We did cohort-specific statistical analyses using confounder models with increasing adjustment for confounder variables, and Cox proportional hazards models with a common protocol. We obtained pooled effect estimates through a random-effects meta-analysis. Findings The total study population consisted of 367 251 participants who contributed 5 118 039 person-years at risk (average follow-up 13.9 years), of whom 29 076 died from a natural cause during follow-up. A significantly increased hazard ratio (HR) for PM2.5 of 1.07 (95% CI 1.02-1.13) per 5 mu g/m(3) was recorded. No heterogeneity was noted between individual cohort effect estimates (I-2 p value=0.95). HRs for PM2.5 remained significantly raised even when we included only participants exposed to pollutant concentrations lower than the European annual mean limit value of 25 mu g/m(3) (HR 1.06, 95% CI 1.00-1.12) or below 20 mu g/m(3) (1.07, 1.01-1.13). Interpretation Long-term exposure to fine particulate air pollution was associated with natural-cause mortality, even within concentration ranges well below the present European annual mean limit value.
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16. |
- Beelen, Rob, et al.
(author)
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Long-term Exposure to Air Pollution and Cardiovascular Mortality An Analysis of 22 European Cohorts
- 2014
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In: Epidemiology. - : Lippincott Williams & Wilkins. - 1044-3983 .- 1531-5487. ; 25:3, s. 368-378
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Journal article (peer-reviewed)abstract
- Background: Air pollution has been associated with cardiovascular mortality, but it remains unclear as to whether specific pollutants are related to specific cardiovascular causes of death. Within the multicenter European Study of Cohorts for Air Pollution Effects (ESCAPE), we investigated the associations of long-term exposure to several air pollutants with all cardiovascular disease (CVD) mortality, as well as with specific cardiovascular causes of death. Methods: Data from 22 European cohort studies were used. Using a standardized protocol, study area-specific air pollution exposure at the residential address was characterized as annual average concentrations of the following: nitrogen oxides (NO2 and NOx); particles with diameters of less than 2.5 mu m (PM2.5), less than 10 mu m (PM10), and 10 mu m to 2.5 mu m (PMcoarse); PM2.5 absorbance estimated by land-use regression models; and traffic indicators. We applied cohort-specific Cox proportional hazards models using a standardized protocol. Random-effects meta-analysis was used to obtain pooled effect estimates. Results: The total study population consisted of 367,383 participants, with 9994 deaths from CVD (including 4,992 from ischemic heart disease, 2264 from myocardial infarction, and 2484 from cerebrovascular disease). All hazard ratios were approximately 1.0, except for particle mass and cerebrovascular disease mortality; for PM2.5, the hazard ratio was 1.21 (95% confidence interval = 0.87-1.69) per 5 mu g/m(3) and for PM10, 1.22 (0.91-1.63) per 10 mu g/m(3). Conclusion: In a joint analysis of data from 22 European cohorts, most hazard ratios for the association of air pollutants with mortality from overall CVD and with specific CVDs were approximately 1.0, with the exception of particulate mass and cerebrovascular disease mortality for which there was suggestive evidence for an association.
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17. |
- Beelen, Rob, et al.
(author)
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Natural-Cause Mortality and Long-Term Exposure to Particle Components : An Analysis of 19 European Cohorts within the Multi-Center ESCAPE Project
- 2015
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In: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 123:6, s. 525-533
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Research review (peer-reviewed)abstract
- Background: Studies have shown associations between mortality and long-term exposure to particulate matter air pollution. Few cohort studies have estimated the effects of the elemental composition of particulate matter on mortality. Objectives: Our aim was to study the association between natural-cause mortality and long-term exposure to elemental components of particulate matter. Methods: Mortality and confounder data from 19 European cohort studies were used. Residential exposure to eight a priori-selected components of particulate matter ( PM) was characterized following a strictly standardized protocol. Annual average concentrations of copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc within PM size fractions <= 2.5 mu m (PM2.5) and <= 10 mu m (PM10) were estimated using land-use regression models. Cohort-specific statistical analyses of the associations between mortality and air pollution were conducted using Cox proportional hazards models using a common protocol followed by meta-analysis. Results: The total study population consisted of 291,816 participants, of whom 25,466 died from a natural cause during follow-up (average time of follow-up, 14.3 years). Hazard ratios were positive for almost all elements and statistically significant for PM2.5 sulfur (1.14; 95% CI: 1.06, 1.23 per 200ng/m(3)). In a two-pollutant model, the association with PM2.5 sulfur was robust to adjustment for PM2.5 mass, whereas the association with PM2.5 mass was reduced. Conclusions: Long-term exposure to PM2.5 sulfur was associated with natural-cause mortality. This association was robust to adjustment for other pollutants and PM2.5.
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18. |
- Bergman, Olle, 1978, et al.
(author)
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Do polymorphisms in transcription factors LMX1A and LMX1B influence the risk for Parkinson's disease?
- 2009
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In: Journal of neural transmission (Vienna, Austria : 1996). - : Springer Science and Business Media LLC. - 1435-1463 .- 0300-9564. ; 116:3, s. 333-8
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Journal article (peer-reviewed)abstract
- The key symptoms of Parkinson's disease (PD) are caused by degeneration of dopamine neurons originating in substantia nigra. Whereas, transcription factor LMX1A is crucial for the differentiation of mesencephalic dopamine neurons, LMX1B appears to be important for both the development and the survival of these cells. The aim of this study was to investigate if genetic variation in LMX1A and LMX1B differs between patients with PD (n = 357) and control subjects (n = 1428) by genotyping 33 single nucleotide polymorphisms (SNPs) in LMX1A and 11 SNPs in LMX1B. Three SNPs in LMX1A and one in LMX1B were associated with PD. After splitting for gender, six SNPs were associated with PD in women and four in men. The significances obtained did not survive correction for multiple testing, and our results should hence be interpreted with caution, but are partly in line with a previous report, and should thus be of sufficient interest to encourage further studies of these genes in PD.
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19. |
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20. |
- Brodaty, Henry, et al.
(author)
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The World of Dementia Beyond 2020
- 2011
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In: Journal of The American Geriatrics Society. - : Wiley. - 0002-8614 .- 1532-5415. ; 59:5, s. 923-927
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Journal article (peer-reviewed)abstract
- Counterpoised against dire projections of the tripling of the prevalence of dementia over the next 40 years are major developments in diagnostic biomarkers, neuroimaging, the molecular biology of Alzheimer's disease (AD), epidemiology of risk and protective factors, and drug treatments—mainly targeting the amyloid pathway, tau protein, and immunotherapy—that may have the potential to modify the progression of AD. Drug combinations and presymptomatic treatments are also being investigated. Previous trials of dementia-modifying drugs have not shown benefit, and even if current Phase III trials prove successful, these drugs will not eradicate other dementias, could (if not curative) increase dementia duration and prevalence, and are unlikely to come onto the market before 2020. In the meantime, delaying the onset of dementia by even 2 years would have significant economic and societal effects. This article provides an overview of current achievements and potentials of basic and clinical research that might affect the development of dementia prevalence and care within the near future.
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21. |
- Brommelhoff, Jessica A, et al.
(author)
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Depression as a risk factor or prodromal feature for dementia? Findings in a population-based sample of Swedish twins.
- 2009
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In: Psychology and aging. - : American Psychological Association (APA). - 0882-7974 .- 1939-1498. ; 24:2, s. 373-84
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Journal article (peer-reviewed)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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22. |
- Calderón-Larrañaga, Amaia, et al.
(author)
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Assessing and Measuring Chronic Multimorbidity in the Older Population : A Proposal for Its Operationalization
- 2017
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In: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press (OUP). - 1079-5006 .- 1758-535X. ; 72:10, s. 1417-1423
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Journal article (peer-reviewed)abstract
- BackgroundAlthough the definition of multimorbidity as the simultaneous presence of two or more chronic diseases is well established, its operationalization is not yet agreed. This study aims to provide a clinically driven comprehensive list of chronic conditions to be included when measuring multimorbidity. MethodsBased on a consensus definition of chronic disease, all four-digit level codes from the International Classification of Diseases, 10th revision (ICD-10) were classified as chronic or not by an international and multidisciplinary team. Chronic ICD-10 codes were subsequently grouped into broader categories according to clinical criteria. Last, we showed proof of concept by applying the classification to older adults from the Swedish National study of Aging and Care in Kungsholmen (SNAC-K) using also inpatient data from the Swedish National Patient Register.ResultsA disease or condition was considered to be chronic if it had a prolonged duration and either (a) left residual disability or worsening quality of life or (b) required a long period of care, treatment, or rehabilitation. After applying this definition in relation to populations of older adults, 918 chronic ICD-10 codes were identified and grouped into 60 chronic disease categories. In SNAC-K, 88.6% had >= 2 of these 60 disease categories, 73.2% had >= 3, and 55.8% had >= 4.ConclusionsThis operational measure of multimorbidity, which can be implemented using either or both clinical and administrative data, may facilitate its monitoring and international comparison. Once validated, it may enable the advancement and evolution of conceptual and theoretical aspects of multimorbidity that will eventually lead to better care.
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23. |
- Calderón-Larrañaga, Amaia, et al.
(author)
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COVID-19 : risk accumulation among biologically and socially vulnerable older populations
- 2020
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In: Ageing Research Reviews. - : Elsevier BV. - 1568-1637 .- 1872-9649. ; 63
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Research review (peer-reviewed)abstract
- Emerging data show that the health and economic impacts of COVID-19 are being disproportionately borne by individuals who are not only biologically, but also socially vulnerable. Based on preliminary data from Sweden and other reports, in this paper we propose a conceptual framework whereby different factors related to bio-logical and social vulnerability may explain the specific COVID-19 burden among older people. There is already some evidence showing large social disparities in the prevention, treatment, prognosis and/or long-term consequences of COVID-19. The remaining question is to what extent these affect older adults specifically. We provide the rationale to address this question with scientific methods and proper study designs, where the interplay between individuals' biomedical status and their social environment is the focus. Only through interdisciplinary research integrating biological, clinical and social data will we be able to provide new insights into the SARS-CoV-2 pandemic and inform actions aimed at reducing older adults' vulnerability to COVID-19 or other similar pandemics in the future.
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24. |
- Calderón-Larrañaga, Amaia, et al.
(author)
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Multimorbidity and functional impairment-bidirectional interplay, synergistic effects and common pathways
- 2019
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In: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 285:3, s. 255-271
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Research review (peer-reviewed)abstract
- This review discusses the interplay between multimorbidity (i.e. co-occurrence of more than one chronic health condition in an individual) and functional impairment (i.e. limitations in mobility, strength or cognition that may eventually hamper a person's ability to perform everyday tasks). On the one hand, diseases belonging to common patterns of multimorbidity may interact, curtailing compensatory mechanisms and resulting in physical and cognitive decline. On the other hand, physical and cognitive impairment impact the severity and burden of multimorbidity, contributing to the establishment of a vicious circle. The circle may be further exacerbated by people's reduced ability to cope with treatment and care burden and physicians' fragmented view of health problems, which cause suboptimal use of health services and reduced quality of life and survival. Thus, the synergistic effects of medical diagnoses and functional status in adults, particularly older adults, emerge as central to assessing their health and care needs. Furthermore, common pathways seem to underlie multimorbidity, functional impairment and their interplay. For example, older age, obesity, involuntary weight loss and sedentarism can accelerate damage accumulation in organs and physiological systems by fostering inflammatory status. Inappropriate use or overuse of specific medications and drug-drug and drug-disease interactions also contribute to the bidirectional association between multimorbidity and functional impairment. Additionally, psychosocial factors such as low socioeconomic status and the direct or indirect effects of negative life events, weak social networks and an external locus of control may underlie the complex interactions between multimorbidity, functional decline and negative outcomes. Identifying modifiable risk factors and pathways common to multimorbidity and functional impairment could aid in the design of interventions to delay, prevent or alleviate age-related health deterioration; this review provides an overview of knowledge gaps and future directions.
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25. |
- Calderón-Larrañaga, Amaia, et al.
(author)
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Psychological correlates of multimorbidity and disability accumulation in older adults
- 2019
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In: Age and Ageing. - : Oxford University Press (OUP). - 0002-0729 .- 1468-2834. ; 48:6, s. 789-796
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Journal article (peer-reviewed)abstract
- Background/Objectives: attitudes toward life and health are emerging as important psychological contributors to health heterogeneity in ageing. We aimed to explore whether different psychological factors were associated with the rate of chronic disease and disability accumulation over time.Design: population-based cohort study between 2001 and 2010.Setting: Swedish National study on aging and care in Kungsholmen.Subjects: adults aged 60 and older (N = 2293).Methods: linear mixed models were employed to study the association of life satisfaction, health outlook, resistance to illness, sickness orientation, and health worry with the rate of accumulation of chronic diseases and impaired basic and instrumental activities of daily living. Models were adjusted for demographic, clinical, social, personality and lifestyle factors. Analyses were repeated after excluding individuals with multimorbidity or disability at baseline.Results: high life satisfaction and positive health outlook were consistently associated with a lower rate of accumulation and progression of multimorbidity (beta -0.064 95% confidence interval [CI] -0.116, -0.011; beta -0.065 95% CI -0.121, -0.008, respectively) and disability (beta -0.063 95% CI -0.098, -0.028; beta -0.042 95% CI -0.079, -0.004, respectively) over time. This was true even for people without multimorbidity or disability at baseline and after adjusting for all covariates.Conclusions: positive attitudes toward life in general and health in particular may be especially important in old age, when the cumulative effects of biological and environmental deficits lead to accelerated health decline. These findings should encourage researchers to use measures of psychological well-being to better understand the multifactorial and diverse process of ageing.
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