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
-
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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26. |
- Calderón-Larrañaga, Amaia, et al.
(author)
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Rapidly developing multimorbidity and disability in older adults : does social background matter?
- 2018
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In: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 283:5, s. 489-499
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Journal article (peer-reviewed)abstract
- Background. Multimorbidity is among the most disabling geriatric conditions. In this study, we explored whether a rapid development of multi morbidity potentiates its impact on the functional independence of older adults, and whether different sociodemographic factors play a role beyond the rate of chronic disease accumulation. Methods. A random sample of persons aged >= 60 years (n = 2387) from the Swedish National study on Aging and Care in Kungsholmen (SNAC-K) was followed over 6 years. The speed of multimorbidity development was estimated as the rate of chronic disease accumulation (linear mixed models) and further dichotomized into the upper versus the three lower rate quartiles. Binomial negative mixed models were used to analyse the association between speed of multimorbidity development and disability (impaired basic and instrumental activities of daily living), expressed as the incidence rate ratio (IRR). The effect of sociodemographic factors, including sex, education, occupation and social network, was investigated. Results. The risk of new activity impairment was higher among participants who developed multi morbidity faster (IRR 2.4, 95% Cl 1.9-3.1) compared with those who accumulated diseases more slowly overtime, even after considering the baseline number of chronic conditions. Only female sex (IRR for women vs. men 1.6, 95% Cl 1.2-2.0) and social network (IRR for poor vs. rich social network 1.7, 95% Cl 1.3-2.2) showed an effect on disability beyond the rate of chronic disease accumulation. Conclusions. Rapidly developing multimorbidity is a negative prognostic factor for disability. However, sociodemographic factors such as sex and social network may determine older adults' reserves of functional ability, helping them to live independently despite the rapid accumulation of chronic conditions.
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27. |
- Caracciolo, Barbara, et al.
(author)
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Cognitive decline, dietary factors and gut-brain interactions
- 2014
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In: Mechanisms of Ageing and Development. - : Elsevier BV. - 0047-6374 .- 1872-6216. ; 136, s. 59-69
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Journal article (peer-reviewed)abstract
- Cognitive decline in elderly people often derives from the interaction between aging-related changes and age-related diseases and covers a large spectrum of clinical manifestations, from intact cognition through mild cognitive impairment and dementia. Epidemiological evidence supports the hypothesis that modifiable lifestyle-related factors are associated with cognitive decline, opening new avenues for prevention. Diet in particular has become the object of intense research in relation to cognitive aging and neurodegenerative disease. We reviewed the most recent findings in this rapidly expanding field. Some nutrients, such as vitamins and fatty acids, have been studied longer than others, but strong scientific evidence of an association is lacking even for these compounds. Specific dietary patterns, like the Mediterranean diet, may be more beneficial than a high consumption of single nutrients or specific food items. A strong link between vascular risk factors and dementia has been shown, and the association of diet with several vascular and metabolic diseases is well known. Other plausible mechanisms underlying the relationship between diet and cognitive decline, such as inflammation and oxidative stress, have been established. In addition to the traditional etiological pathways, new hypotheses, such as the role of the intestinal microbiome in cognitive function, have been suggested and warrant further investigation.
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28. |
- Caracciolo, Barbara, et al.
(author)
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Differential distribution of subjective and objective cognitive impairment in the population : a nation-wide twin-study
- 2012
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In: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 29:2, s. 393-403
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Journal article (peer-reviewed)abstract
- We report the prevalence of subjective cognitive impairment (SCI) and cognitive impairment no dementia (CIND), their socio-demographic profile, and the contribution of genetic background and shared familial environment to SCI and CIND. Subjects were 11,926 dementia-free twin individuals aged ≥65 from the Swedish Twin Registry. SCI was defined as subjective complaint of cognitive change without objective cognitive impairment and CIND was defined according to current criteria. Overall prevalence rates of SCI and CIND were 39% (95% CI 38-39%) and 25% (95% CI 24-25%). In multivariate GEE models, both SCI and CIND were older compared with people without any cognitive impairment. CIND were also less educated, more likely to be unmarried and to have lower socioeconomic status (SES). SCI individuals differed from persons with CIND as they were older, more educated, more likely to be married, and to have higher SES. Co-twin control analysis, which corrects for common genetic and shared environmental background, confirmed the association of low education with CIND. Probandwise concordance for SCI and CIND was 63% and 52% in monozygotic twins, 63% and 50% in dizygotic same-sex twins, and 42% and 29% in dizygotic unlike-sex twins. Tetrachoric correlations showed no significant differences between monozygotic and dizygotic same-sex twins. We conclude that subjective and objective cognitive impairment are both highly prevalent among nondemented elderly yet have distinct sociodemographic profiles. Shared environmental influences rather than genetic background play a role in the occurrence of SCI and CIND.
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29. |
- Caracciolo, Barbara, et al.
(author)
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Relationship of Subjective Cognitive Impairment and Cognitive Impairment No Dementia to Chronic Disease and Multimorbidity in a Nation-Wide Twin Study
- 2013
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In: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 36:2, s. 275-284
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Journal article (peer-reviewed)abstract
- We investigated the relation of subjective cognitive impairment (SCI) and cognitive impairment no dementia (CIND) to common chronic diseases of the elderly and multimorbidity, and assessed the contribution of genetic background and shared familial environment to these associations. Subjects were 11,379 dementia-free twin individuals aged >= 65 from the Swedish Twin Registry. SCI was defined as subjective complaint of cognitive change without objective cognitive impairment and CIND was defined according to current criteria. In unmatched, fully-adjusted regression models, mental, musculoskeletal, respiratory, and urological diseases were all significantly associated with increased odds ratios (ORs) of SCI and CIND. Circulatory and gastrointestinal diseases were related to SCI only, while endocrine diseases were associated with CIND. The adjusted ORs of multimorbidity were 2.1 [95% confidence intervals (95% CI): 1.8-2.3] for SCI and 1.5 for CIND (95% CI: 1.3-1.8). A dose-dependent relationship was observed between number of chronic diseases and ORs for SCI but not for CIND. In co-twin control analyses, the chronic diseases-SCI association was largely unchanged. On the other hand, the chronic diseases-CIND association was no longer statistically significant, except for cancer, where an increased OR was observed. In conclusion, chronic morbidity is associated with both SCI and CIND but disease profiles do not always overlap between the two cognitive syndromes. The association is stronger when diseases co-occur, especially for SCI. Genetic and early-life environmental factors may partially explain the association of CIND but not that of SCI with chronic diseases.
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30. |
- Cavallin, Lena, et al.
(author)
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Comparison between visual assessment of MTA and hippocampal volumes in an elderly, non-demented population
- 2012
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In: Acta Radiologica. - : SAGE Publications. - 0284-1851 .- 1600-0455. ; 53:5, s. 573-579
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Journal article (peer-reviewed)abstract
- Background It is important to have a replicable easy method for monitoring atrophy progression in Alzheimer's disease. Volumetric methods for calculating hippocampal volume are time-consuming and commonly used in research. Visual assessments of medial temporal lobe atrophy (vaMTA) is a rapid method for clinical use. This method has not been tested in a large non-demented population in comparison with volumetry mesurements. Since hippocampal volume decreases with time even in normal aging there is also a need to study the normal age differences of medial temporal lobe atrophy. Purpose To compare visual assessment of medial temporal lobe atrophy (vaMTA) with hippocampal volume in a healthy, non-demented elderly population. To describe normal ageing using vaMTA. Material and Methods Non-demented individuals aged 60, 66, 72, 78, 81, 84, and ≥87 years old were recruited from the Swedish National study on Ageing and Care in Kungsholmen (SNAC-K), Sweden. Standard magnetic resonance imaging (MRI) scans, vaMTA, and calculations of hippocampal volumes were performed in 544 subjects. Results Significant correlation (rs = −0.32, P < 0.001, sin; and rs = −0.26, P < 0.001, dx) was found between hippocampal volume measurements and vaMTA. In normal ageing, almost 95% of ≤66-year-olds had a medial temporal lobe atrophy (MTA) score ≤1, with possible scores ranging from 0 to 4. Subjects aged 72, 78, and 81 years scored ≤2, while the two oldest age groups had scores ≤3. Conclusion There was a highly significant correlation between volumetric measurements of the hippocampus and MTA scoring. In normal ageing, there is increasing MTA score. For non-demented elderly individuals ≤70 years, an MTA score of 0–1 may be considered normal, compared with MTA ≤2 for 70–80-years and MTA 3 for >80-year-old individuals.
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31. |
- Cesaroni, Giulia, et al.
(author)
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Long term exposure to ambient air pollution and incidence of acute coronary events : prospective cohort study and meta-analysis in 11 European cohorts from the ESCAPE Project
- 2014
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In: The BMJ. - : BMJ. - 1756-1833. ; 348, s. f7412-
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Journal article (peer-reviewed)abstract
- Objectives To study the effect of long term exposure to airborne pollutants on the incidence of acute coronary events in 11 cohorts participating in the European Study of Cohorts for Air Pollution Effects (ESCAPE). Design Prospective cohort studies and meta-analysis of the results. Setting Cohorts in Finland, Sweden, Denmark, Germany, and Italy. Participants 100 166 people were enrolled from 1997 to 2007 and followed for an average of 11.5 years. Participants were free from previous coronary events at baseline. Main outcome measures Modelled concentrations of particulate matter <2.5 mu m (PM2.5), 2.5-10 mu m (PMcoarse), and <10 mu m (PM10) in aerodynamic diameter, soot (PM2.5 absorbance), nitrogen oxides, and traffic exposure at the home address based on measurements of air pollution conducted in 2008-12. Cohort specific hazard ratios for incidence of acute coronary events (myocardial infarction and unstable angina) per fixed increments of the pollutants with adjustment for sociodemographic and lifestyle risk factors, and pooled random effects meta-analytic hazard ratios. Results 5157 participants experienced incident events. A 5 mu g/m(3) increase in estimated annual mean PM2.5 was associated with a 13% increased risk of coronary events (hazard ratio 1.13, 95% confidence interval 0.98 to 1.30), and a 10 mu g/m(3) increase in estimated annual mean PM10 was associated with a 12% increased risk of coronary events (1.12, 1.01 to 1.25) with no evidence of heterogeneity between cohorts. Positive associations were detected below the current annual European limit value of 25 mu g/m(3) for PM2.5 (1.18, 1.01 to 1.39, for 5 mu g/m(3) increase in PM2.5) and below 40 mu g/m(3) for PM10 (1.12, 1.00 to 1.27, for 10 mu g/m(3) increase in PM10). Positive but non-significant associations were found with other pollutants. Conclusions Long term exposure to particulate matter is associated with incidence of coronary events, and this association persists at levels of exposure below the current European limit values.
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32. |
- Cruz-Jentoft, Alfonso J., et al.
(author)
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Using the Multidimensional Prognostic Index (MPI) to improve cost-effectiveness of interventions in multimorbid frail older persons : results and final recommendations from the MPI_AGE European Project
- 2020
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In: Aging Clinical and Experimental Research. - : Springer Science and Business Media LLC. - 1594-0667 .- 1720-8319. ; 32:5, s. 861-868
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Journal article (peer-reviewed)abstract
- MPI_AGE is a European Union co-funded research project aimed to use the Multidimensional Prognostic Index (MPI), a validated Comprehensive Geriatric Assessment (CGA)-based prognostic tool, to develop predictive rules that guide clinical and management decisions in older people in different European countries. A series of international studies performed in different settings have shown that the MPI is useful to predict mortality and risk of hospitalization in community-dwelling older subjects at population level. Furthermore, studies performed in older people who underwent a CGA before admission to a nursing home or receiving homecare services showed that the MPI successfully identified groups of persons who could benefit, in terms of reduced mortality, of specific therapies such as statins in diabetes mellitus and coronary artery disease, anticoagulants in atrial fibrillation and antidementia drugs in cognitive decline. A prospective trial carried out in nine hospitals in Europe and Australia demonstrated that the MPI was able to predict not only in-hospital and long-term mortality, but also institutionalization, re-hospitalization and receiving homecare services during the one-year follow-up after hospital discharge. The project also explored the association between MPI and mortality in hospitalized older patients in need of complex procedures such as transcatheter aortic valve implantation or enteral tube feeding. Evidence from these studies has prompted the MPI_AGE Investigators to formulate recommendations for healthcare providers, policy makers and the general population which may help to improve the cost-effectiveness of appropriate health care interventions for older patients.
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33. |
- Dekhtyar, Serhiy, et al.
(author)
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Association Between Speed of Multimorbidity Accumulation in Old Age and Life Experiences : A Cohort Study
- 2019
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In: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 188:9, s. 1627-1636
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Journal article (peer-reviewed)abstract
- Rapidly accumulating multiple chronic conditions (multimorbidity) during aging are associated with many adverse outcomes. We explored the association between 4 experiences throughout life-childhood socioeconomic circumstances, early-adulthood education, midlife occupational stress, and late-life social network-and the speed of chronic disease accumulation. We followed 2,589 individuals aged >= 60 years from the Swedish National Study on Aging and Care in Kungsholmen for 9 years (2001-2013). Information on life experiences was collected from detailed life-history interviews. Speed of disease accumulation was operationalized as the change in the count of chronic conditions obtained from clinical examinations, medical histories, laboratory data, drug use, and register linkages over 9 years. Linear mixed models were used to analyze the data. Speed of disease accumulation was lower in individuals with more than elementary education (for secondary, beta x time = -0.065, 95% CI: -0.126, -0.004; for university, beta x time = -0.118, 95% CI: -0.185, -0.050); for active occupations compared with high-strain jobs (beta x time = -0.078, 95% CI: -0.138, -0.017); and for richer social networks (for moderate tertile, beta x time = -0.102, 95% CI: -0.149, -0.055; for highest tertile, beta x time = -0.135, 95% CI: -0.182, -0.088). The association between childhood circumstances and speed of disease accumulation was attenuated by later-life experiences. Diverse experiences throughout life might decelerate chronic disease accumulation during aging.
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34. |
- Dekhtyar, Serhiy, et al.
(author)
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Childhood school performance, education and occupational complexity : a life-course study of dementia in the Kungsholmen Project
- 2016
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In: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 45:4, s. 1207-1215
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Journal article (peer-reviewed)abstract
- Background: Cognitive reserve hypothesis predicts that intellectually demanding activities over the life course protect against dementia. We investigate if childhood school performance remains associated with dementia once education and occupational complexity are taken into account. Methods: A cohort of 440 individuals aged 75+ from the Kungsholmen Project was followed up for 9 years to detect dementia. To measure early-life contributors to reserve, we used grades at age 9-10 extracted from the school archives. Data on formal education and occupational complexity were collected at baseline and first follow-up. Dementia was ascertained through comprehensive clinical examination. Cox models estimated the relationship between life-course cognitive reserve measures and dementia. Results: Dementia risk was elevated [hazard ratio (HR): 1.54, 95% confidence interval (CI): 1.03 to 2.29] in individuals with low early-life school grades after adjustment for formal educational attainment and occupational complexity. Secondary education was associated with a lower risk of dementia (HR: 0.72, 95% CI: 0.50 to 1.03), although the effects of post-secondary and university degrees were indistinguishable from baseline. Occupational complexity with data and things was not related to dementia. However, an association was found between high occupational complexity with people and dementia, albeit only in women (HR: 0.39, 95% CI: 0.14 to 0.99). The pattern of results remained unchanged after adjustment for genetic susceptibility, comorbidities and depressive symptoms. Conclusion: Low early-life school performance is associated with an elevated risk of dementia, independent of subsequent educational and occupational attainment.
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35. |
- Dekhtyar, Serhiy, et al.
(author)
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Genetic risk of dementia mitigated by cognitive reserve : A cohort study
- 2019
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In: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 86:1, s. 68-78
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Journal article (peer-reviewed)abstract
- Objective We investigated whether cognitive reserve modifies the risk of dementia attributable to apolipoprotein epsilon 4 (APOE-epsilon 4), a well-known genetic risk factor for dementia. Methods We followed 2,556 cognitively intact participants aged >= 60 years from the ongoing prospective community-based Swedish National Study on Aging and Care in Kungsholmen (SNAC-K). Dementia was ascertained through clinical and neuropsychological assessments and diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria. Structural equation modeling was used to generate a cognitive reserve indicator from 4 previously validated contributors: early life education, midlife substantive work complexity, late life leisure activities, and late life social networks. Cox proportional hazard models estimated dementia risk in relation to cognitive reserve indicator. The interaction between the cognitive reserve indicator and APOE-epsilon 4 was assessed on multiplicative and additive scales. Results After an average of 6.3 years (range = 2.1-10.7) of follow-up, 232 dementia cases were ascertained. Relative to individuals in the lowest tertile of cognitive reserve indicator, those with moderate and high reserve were at a reduced risk of dementia. There was no multiplicative interaction between APOE-epsilon 4 status and cognitive reserve indicator (p = 0.113). Additive interaction was statistically significant. Relative to APOE-epsilon 4 carriers with low cognitive reserve, epsilon 4 carriers with high reserve had a reduced risk of dementia (hazard ratio [HR] = 0.28, 95% confidence interval [CI] = 0.13-0.59). The magnitude of risk reduction was similar in epsilon 4 noncarriers with a high cognitive reserve indicator (HR = 0.24, 95% CI = 0.15-0.40). Interpretation Lifelong engagement in reserve-enhancing activities attenuates the risk of dementia attributable to APOE-epsilon 4. Promoting cognitive reserve might be especially effective in subpopulations with high genetic risk of dementia. ANN NEUROL 2019
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36. |
- Dimakopoulou, Konstantina, et al.
(author)
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Air Pollution and Nonmalignant Respiratory Mortality in 16 Cohorts within the ESCAPE Project
- 2014
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In: American Journal of Respiratory and Critical Care Medicine. - : American Thoracic Society. - 1073-449X .- 1535-4970. ; 189:6, s. 684-696
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Journal article (peer-reviewed)abstract
- Rationale: Prospective cohort studies have shown that chronic exposure to particulate matter and traffic-related air pollution is associated with reduced survival. However, the effects on nonmalignant respiratory mortality are less studied, and the data reported are less consistent. Objectives: We have investigated the relationship of long-term exposure to air pollution and nonmalignant respiratory mortality in 16 cohorts with individual level data within the multicenter European Study of Cohorts for Air Pollution Effects (ESCAPE). Methods: Data from 16 ongoing cohort studies from Europe were used. The total number of subjects was 307,553. There were 1,559 respiratory deaths during follow-up. Measurements and Main Results: Air pollution exposure was estimated by land use regression models at the baseline residential addresses of study participants and traffic-proximity variables were derived from geographical databases following a standardized procedure within, the ESCAPE study. Cohort-specific hazard ratios obtained by Cox proportional hazard models from standardized individual cohort analyses were combined using metaanalyses. We found no significant associations between air pollution exposure and nonmalignant respiratory mortality. Most hazard ratios were slightly below unity, with the exception of the traffic-proximity indicators. Conclusions: In this study of 16 cohorts, there was no-association between air pollution exposure and nonmalignant respiratory mortality.
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37. |
- Ding, Mozhu, et al.
(author)
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Atrial fibrillation and use of antithrombotic medications in older people : A population-based study
- 2017
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In: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 249, s. 173-178
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Journal article (peer-reviewed)abstract
- Background: Trends in the use of antithrombotic drugs in elderly patients with atrial fibrillation (AF) are largely unknown. We estimated the prevalence of AF in an older population, and examined whether use of anticoagulant and antiplatelet drugs in older AF patients has changed over time. Methods: Data from the population-based Swedish National study on Aging and Care in Kungsholmen (n = 3363, age = 60 years, 64.9% women) were used (2001-2004 and 2007-2010). AF cases were identified through 12-lead electrocardiogram, physician examinations, and patient register records (ICD-10 code I48). We used the CHADS(2) and CHA(2)DS(2)-VASc scores to estimate stroke risk, and an incomplete HAS-BLED score to estimate bleeding risk. Results: At baseline (2001-2004), 328 persons (9.8%) were ascertained to have AF. The prevalence of AF increased significantly with age from 2.8% in people aged 60-66 years to 21.2% in those = 90 years, and was more common in men than in women (11.2% vs. 9.0%). Among AF patients with CHADS2 score = 2 at baseline, 25% were taking anticoagulant drugs and 54% were taking antiplatelet drugs. High bleeding risk was significantly associated with not using anticoagulant drugs in AF patients (multi-adjusted OR = 2.50, p = 0.015). Between 2001-2004 and 2007-2010, use of anticoagulant drugs increased significantly, especially in AF patients with CHA2DS2-VASc score >= 2 (23% vs. 33%, p = 0.008) and in those with HAS-BLED score <3 (32% vs. 53%, p = 0.004). Conclusion: AF is common among old people. The use of anticoagulant drugs increased over time in AF patients, yet still two-thirds of those with high stroke risk remained untreated.
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38. |
- Ding, Mozhu, et al.
(author)
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Atrial fibrillation, antithrombotic treatment, and cognitive aging : A population-based study
- 2018
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In: Neurology. - 0028-3878 .- 1526-632X. ; 91:19, s. e1732-e1740
-
Journal article (peer-reviewed)abstract
- ObjectiveTo examine the association of atrial fibrillation (AF) with cognitive decline and dementia in old age, and to explore the cognitive benefit of antithrombotic treatment in patients with AF.MethodsThis population-based cohort study included 2,685 dementia-free participants from the Swedish National Study on Aging and Care in Kungsholmen, who were regularly examined from 2001-2004 to 2010-2013. AF was ascertained from clinical examination, ECG, and patient registry. Global cognitive function was assessed using the Mini-Mental State Examination. We followed the DSM-IV criteria for the diagnosis of dementia, the NINDS-AIREN (National Institute of Neurological Disorders and Stroke and Association Internationale pour la Recherche et l'Enseignement en Neurosciences) criteria for vascular dementia, and the NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association) criteria for Alzheimer disease. Data were analyzed using multiple linear mixed-effects and Cox regression models.ResultsWe identified 243 participants (9.1%) with AF at baseline. During the 9-year follow-up period, 279 participants (11.4%) developed AF and 399 (14.9%) developed dementia. As a time-varying variable, AF was significantly associated with a faster annual Mini-Mental State Examination decline (beta coefficient = -0.24, 95% confidence interval [ CI]: -0.31 to -0.16) and an increased hazard ratio (HR) of all-cause dementia (HR = 1.40, 95% CI: 1.11-1.77) and vascular and mixed dementia (HR = 1.88, 95% CI: 1.09-3.23), but not Alzheimer disease (HR = 1.33, 95% CI: 0.92-1.94). Among people with either prevalent or incident AF, use of anticoagulant drugs, but not antiplatelet treatment, was associated with a 60% decreased risk of dementia (HR = 0.40, 95% CI: 0.18-0.92).Conclusion AF is associated with a faster global cognitive decline and an increased risk of dementia in older people. Use of anticoagulant drugs may reduce dementia risk in patients with AF.
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39. |
- Ding, Mozhu, et al.
(author)
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Cerebral Small Vessel Disease Associated With Atrial Fibrillation Among Older Adults : A Population-Based Study.
- 2021
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In: Stroke. - : American Heart Association. - 0039-2499 .- 1524-4628. ; 52:8, s. 2685-2689
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Journal article (peer-reviewed)abstract
- BACKGROUND AND PURPOSE: Cerebral small vessel disease, as a potential mechanism underlying the association between atrial fibrillation (AF) and dementia, remains poorly investigated. In this cohort study, we sought to examine the association between AF and cerebral small vessel disease markers among older adults.METHODS: Data on 336 participants (age ≥60 years, mean 70.2 years; 60.2% women) free of dementia, disability, and cerebral infarcts were derived from the population-based Swedish National Study on Aging and Care in Kungsholmen. Structural brain magnetic resonance imaging examinations were performed at baseline (2001-2004) and follow-ups (2004-2007 and 2007-2010). Magnetic resonance imaging markers of cerebral small vessel disease included perivascular spaces, lacunes, and volumes of white matter hyperintensities, lateral ventricles, and total brain tissue. AF was assessed at baseline and follow-ups through clinical examinations, electrocardiogram, and medical records. Data were analyzed using linear mixed-effects models.RESULTS: At baseline, 18 persons (5.4%) were identified to have prevalent AF and 17 (5.6%) developed incident AF over the 6-year follow-up. After multivariable adjustment, AF was significantly associated with a faster annual increase in white matter hyperintensities volume (β coefficient=0.45 [95% CI, 0.04-0.86]) and lateral ventricular volume (0.58 [0.13-1.02]). There was no significant association of AF with annual changes in perivascular spaces number (β coefficient=0.53 [95% CI, -0.27 to 1.34]) or lacune number (-0.01 [-0.07 to 0.05]).CONCLUSIONS: Independent of cerebral infarcts, AF is associated with accelerated progression of white matter lesions and ventricular enlargement among older adults.
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40. |
- Ding, Mozhu, et al.
(author)
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Tracing temporal trends in dementia incidence over 25 years in central Stockholm, Sweden
- 2020
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In: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 16:5, s. 770-778
-
Journal article (peer-reviewed)abstract
- Introduction: Recent reports from high-income countries have suggested a declining incidence of dementia.Methods: Trends in dementia incidence over 25 years among people >= 75 years of age were examined using two population-based cohort studies: the Kungsholmen Project (KP, n = 1473, 1987-1998) and the Swedish National study on Aging and Care in Kungsholmen (SNAC-K, n = 1746, 2001-2013).Results: We identified 440 (29.9%) and 388 (22.2%) incident dementia cases in the KP and SNAC-K cohorts, respectively. The incidence of dementia declined by 30% (hazard ratio [HR] = 0.70; 95% confidence interval [CI] 0.61-0.80) during the second decade. Adjustment of education, psychosocial working conditions, lifestyle, and vascular diseases did not substantially change the results (HR = 0.77, 95% CI 0.65-0.90). This decline was observed particularly in women and people with elementary education.Discussion: Our study provides direct evidence of a declining trend in dementia incidence. Improved cognitive reserve and cardiovascular health could partially explain the decline.
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41. |
- Dove, Abigail, et al.
(author)
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Association between social isolation and reduced mental well-being in Swedish older adults during the first wave of the COVID-19 pandemic : the role of cardiometabolic diseases
- 2022
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In: Aging. - : Impact Journals, LLC. - 1945-4589. ; 14:6, s. 2462-2474
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Journal article (peer-reviewed)abstract
- Social isolation has been recommended as a strategy for reducing COVID-19 risk, but it may have unintended consequences for mental well-being. We explored the relationship between social isolation and symptoms of depression and anxiety in older adults during the first wave of the COVID-19 pandemic and assessed the role of cardiometabolic diseases (CMDs) in this association. Between May and September 2020, 1,190 older adults from the Swedish National Study on Aging and Care in Kungsholmen were surveyed about their behaviors and health consequences during the first wave of the COVID-19 pandemic. In total, 913 (76.7%) participants reported socially isolating at home to avoid infection during this period. Social isolation was associated with a greater likelihood of reduced mental well-being (i.e., feelings of depression or anxiety) (OR: 1.74, 95% CI: 1.15-2.65). In joint exposure analysis, there was a significant likelihood of reduced mental well-being only among people who were socially isolating and had CMDs (OR: 2.13, 95% CI: 1.22-3.71) (reference: not isolating, CMD-free). In conclusion, social isolation as a COVID-19 prevention strategy was related to reduced mental well-being in an urban sample of Swedish older adults, especially among individuals with CMDs.
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42. |
- Dove, Abigail, et al.
(author)
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Cardiometabolic multimorbidity accelerates cognitive decline and dementia progression
- 2023
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In: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:3, s. 821-830
-
Journal article (peer-reviewed)abstract
- Introduction: Cardiometabolic diseases (CMDs) have been individually associated with adverse cognitive outcomes, but their combined effect has not been investigated.Methods: A total of 2577 dementia-free participants 60 years of age or older were followed for 12 years to observe changes in cognitive function and to detect incident cognitive impairment, no dementia (CIND) and dementia. CMDs (including type 2 diabetes, heart disease, and stroke) were assessed at baseline through medical records and clinical examinations. Cardiometabolic multimorbidity was defined as the presence of two or more CMDs. Data were analyzed using multi-adjusted linear mixed-effects models, Cox regression, and Laplace regression.Results: CMD multimorbidity was associated with cognitive decline, CIND (hazard ratio [HR] 1.73; 95% confidence interval CI 1.23 to 2.44), and its progression to dementia (HR 1.86; 95% CI 1.17 to 2.97). CMD multimorbidity accelerated the onset of CIND by 2.3 years and dementia by 1.8 years.Conclusions: CMD multimorbidity accelerates cognitive decline and increases the risk of both CIND and its conversion to dementia.
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43. |
- Ek, Stina, et al.
(author)
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Risk Factors for Injurious Falls in Older Adults : The Role of Sex and Length of Follow-Up
- 2019
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In: Journal of The American Geriatrics Society. - : Wiley. - 0002-8614 .- 1532-5415. ; 67:2, s. 246-253
-
Journal article (peer-reviewed)abstract
- OBJECTIVES: To identify sex-specific associations between risk factors and injurious falls over the short (<4 years) and long (4-10 years) term.DESIGN: Longitudinal cohort study between 2001 and 2011.SETTING: Swedish National Study on Aging and Care, Kungsholmen, Sweden.PARTICIPANTS: Community-dwelling adults aged 60 and older (N = 3,112).MEASUREMENTS: An injurious fall was defined as a fall that required inpatient or outpatient care. Information was collected on participant and exposure characteristics using structured interviews, clinical examinations, and physical function tests at baseline.RESULTS: The multivariate model showed that, in the short term, living alone (hazard ratio (HR)=1.83, 95% confidence interval (CI)=1.13-2.96), dependency in instrumental activities of daily living (IADLs) (HR=2.59, 95% CI=1.73-3.87), and previous falls (HR=1.71, 95% CI=1.08-2.72) were independently associated with injurious falls in women. Low systolic blood pressure (HR=1.96, 95% CI=1.04-3.71), impaired chair stands (HR=3.00, 95% CI=1.52-5.93), and previous falls (HR=2.81, 95% CI=1.32-5.97) were associated with injurious falls in men. Long-term risk factors were underweight (HR=2.03, 95% CI=1.40-2.95), cognitive impairment (HR=1.49, 95% CI=1.08-2.06), fall-risk increasing drugs (HR=1.67, 95% CI=1.27-2.20 for >= 2 drugs), and IADL dependency (HR=1.58, 95% CI=1.32-5.97) for women and smoking (HR=1.71, 95% CI=1.03-2.84), heart disease (HR=2.20, 95% CI=1.5-3.24), impaired balance (HR=1.68, 95% CI=1.08-2.62), and a previous fall (HR=3.61, 95% CI=1.98-6.61) for men.CONCLUSION: Men and women have different fall risk profiles, and these differences should be considered when developing preventive strategies. Some risk factors were more strongly predictive of injurious falls over shorter than longer periods and vice versa, suggesting that it may be possible to identify older men and women at short-and long-term risk of injurious falls.
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44. |
- Ek, Stina, et al.
(author)
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Risk Profiles for Injurious Falls in People Over 60 : A Population-Based Cohort Study
- 2018
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In: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press (OUP). - 1079-5006 .- 1758-535X. ; 73:2, s. 233-239
-
Journal article (peer-reviewed)abstract
- Background: Although falls in older adults are related to multiple risk factors, these factors have commonly been studied individually. We aimed to identify risk profiles for injurious falls in older adults by detecting clusters of established risk factors and quantifying their impact on fall risk. Methods: Participants were 2,566 people, aged 60 years and older, from the population-based Swedish National Study on Aging and Care in Kungsholmen. Injurious falls was defined as hospitalization for or receipt of outpatient care because a fall. Cluster analysis was used to identify aggregation of possible risk factors including chronic diseases, fall-risk increasing drugs (FRIDs), physical and cognitive impairments, and lifestyle-related factors. Associations between the clusters and injurious falls over 3, 5, and 10 years were estimated using flexible parametric survival models. Results: Five clusters were identified including: a healthy, a well-functioning with multimorbidity, a well-functioning, with multimorbidity and high FRID consumption, a physically and cognitively impaired, and a disabled cluster. The risk of injurious falls for all groups was significantly higher than for the first cluster of healthy individuals in the reference category. Hazard ratios (95% confidence intervals) ranged from 1.71 (1.02-2.66) for the second cluster to 12.67 (7.38-21.75) for the last cluster over 3 years of follow-up. The highest risk was observed in the last two clusters with high burden of physical and cognitive impairments. Conclusion: Risk factors for injurious fall tend to aggregate, representing different levels of risk for falls. Our findings can be useful to tailor and prioritize clinical and public health interventions.
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45. |
- Ekman, Sirkka-Liisa, et al.
(author)
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Alzheimer
- 2011
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Reports (other academic/artistic)
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46. |
- Ferencz, Beata, et al.
(author)
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The influence of APOE and TOMM40 polymorphisms on hippocampal volume and episodic memory in old age
- 2013
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In: Frontiers in Human Neuroscience. - : Frontiers Media SA. - 1662-5161. ; 7
-
Journal article (peer-reviewed)abstract
- Mitochondrial dysfunction is implicated in neurodegenerative disorders, such as Alzheimer's disease (AD). Translocase of outer mitochondrial membrane 40 (TOMM40) may be influential in this regard by influencing mitochondrial neurotoxicity. Little is known about the influence of the TOMM40 gene on hippocampal (HC) volume and episodic memory (EM), particularly in healthy older adults. Thus, we sought to discern the influence of TOMM40 single nucleotide polymorphisms (SNPs), which have previously been associated with medial temporal lobe integrity (rs11556505 and rs2075650), on HC volume and EM. The study sample consisted of individuals from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K) who were free of dementia and known neurological disorders, and 6087 years of age (n = 424). EM was measured by using a 16-item word list with a 2-min free recall period and delineation of the HC was performed manually. The influence of Apolipoprotein E (APOE) and TOMM40 was assessed by 2 x 2 ANOVAs and partial correlations. There was no effect of APOE and TOMM40 on EM performance and HC volume. However, partial correlations revealed that HC volume was positively associated with free recall performance (r = 0.21, p < 0.01, r(2) = 0.04). When further stratified for TOMM40, the observed association between HC volume and free recall in APOE epsilon 4 carriers was present in combination with TOMM40 rs11556505 any T (r = 0.28, p < 0.01, R-2 = 0.08) and rs2075650 any G (r = 0.28, p < 0.01, R-2 = 0.08) risk alleles. This pattern might reflect higher reliance on HC volume for adequate EM performance among APOE epsilon 4 carriers with additional TOMM40 risk alleles suggesting that the TOMM40 gene cannot merely be considered a marker of APOE genotype. Nevertheless, neither APOE nor TOMM40 influenced HC volume or EM in this population-based sample of cognitively intact individuals over the age of 60.
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47. |
- Ferrari, Camilla, et al.
(author)
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Alzheimer's Disease Progression : Factors Influencing Cognitive Decline
- 2018
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In: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 61:2, s. 785-791
-
Journal article (peer-reviewed)abstract
- Background:Alzheimer's disease (AD) patients present high variability in the rate of cognitive decline. Despite the wide knowledge on factors influencing dementia risk, little is known on what accounts for AD progression. Previous studies on this topic have mainly analyzed each factor separately without taking into account the interaction between genetic and non-genetic factors.Objective:The aim of the present study is to evaluate the role of demographic, clinical, therapeutic, and genetic factors and their interaction on cognitive decline among newly diagnosed AD patients.Methods:We retrospectively selected 160 AD patients diagnosed at the Neurology Unit of Careggi University Hospital of Florence. We evaluated the occurrence of rapid cognitive changes defined as the worsening of more than four points at the Mini-Mental State Examination after 2-year follow up period.Results:Among the 160 AD patients, 50% presented rapid disease progression. Extrapyramidal signs at disease onset were predictors of worse outcome (OR 2.2), especially among Apolipoprotein E (APOE) epsilon 4 allele carriers, while the presence of family history for dementia decreased the risk of rapid progression by about 50%. Higher educated epsilon 4-carriers showed a slower AD progression. We identified the chronic use of aspirin as potential secondary preventative strategy for the non epsilon 4-carriers.Conclusion:At dementia onset, some clinical and demographic data can be predictors of future progression. The outcomes of the present study support the already hypothesized interaction between genetic and non-genetic factors during disease course and suggest genetic-based approaches.
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48. |
- Ferrari, Camilla, et al.
(author)
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How can elderly apolipoprotein E epsilon 4 carriers remain free from dementia?
- 2013
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In: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 34:1, s. 13-21
-
Journal article (peer-reviewed)abstract
- Apolipoprotein E (APOE) epsilon 4 is a major risk factor for Alzheimer's disease (AD) and dementia, but not all epsilon 4 carriers develop dementia. We sought to identify factors that may play a role in modifying the risk of dementia due to epsilon 4. A cognitively intact cohort (n = 932, age >= 75) was followed for 9 years to detect incident dementia cases. At baseline, information on education, leisure activities, and vascular risk factors was collected, and APOE was genotyped. During the follow-up, 324 subjects developed dementia, including 247 AD cases. The hazard ratio (HR, 95% confidence interval [95% CI]) of dementia related to the epsilon 4 was 1.39 (1.11-1.76), while the risk was reduced when epsilon 4 carriers had high education, no vascular risk factors, or high score of leisure activities. Among epsilon 4 carriers, the multiadjusted HRs of dementia that were associated with high education, high level of leisure activities, and absence of vascular risk factors were 0.59 (0.40-0.87), 0.49 (0.29-0.85), and 0.61 (0.41-0.90), respectively. The epsilon 4 carriers with these factors had about 1.2 years delayed time to dementia onset compared with those without these factors. High education, active leisure activities, or maintaining vascular health seems to reduce the risk of dementia related to APOE epsilon 4. The epsilon 4 carriers with these characteristics appear to have similar dementia-free survival time to non-epsilon 4 carriers.
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49. |
- Ferreira, Daniel, et al.
(author)
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The interactive effect of demographic and clinical factors on hippocampal volume : A multicohort study on 1958 cognitively normal individuals
- 2017
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In: Hippocampus. - : Wiley. - 1050-9631 .- 1098-1063. ; 27:6, s. 653-667
-
Journal article (peer-reviewed)abstract
- Alzheimer's disease is characterized by hippocampal atrophy. Other factors also influence the hippocampal volume, but their interactive effect has not been investigated before in cognitively healthy individuals. The aim of this study is to evaluate the interactive effect of key demographic and clinical factors on hippocampal volume, in contrast to previous studies frequently investigating these factors in a separate manner. Also, to investigate how comparable the control groups from ADNI, AIBL, and AddNeuroMed are with five population-based cohorts. In this study, 1958 participants were included (100 AddNeuroMed, 226 ADNI, 155 AIBL, 59 BRC, 295 GENIC, 279 BioFiNDER, 398 PIVUS, and 446 SNAC-K). ANOVA and random forest were used for testing between-cohort differences in demographic-clinical variables. Multiple regression was used to study the influence of demographic-clinical variables on hippocampal volume. ANCOVA was used to analyze whether between-cohort differences in demographic-clinical variables explained between-cohort differences in hippocampal volume. Age and global brain atrophy were the most important variables in explaining variability in hippocampal volume. These variables were not only important themselves but also in interaction with gender, education, MMSE, and total intracranial volume. AddNeuroMed, ADNI, and AIBL differed from the population-based cohorts in several demographic-clinical variables that had a significant effect on hippocampal volume. Variability in hippocampal volume in individuals with normal cognition is high. Differences that previously tended to be related to disease mechanisms could also be partly explained by demographic and clinical factors independent from the disease. Furthermore, cognitively normal individuals especially from ADNI and AIBL are not representative of the general population. These findings may have important implications for future research and clinical trials, translating imaging biomarkers to the general population, and validating current diagnostic criteria for Alzheimer's disease and predementia stages.
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50. |
- Forsell, Charlotte, et al.
(author)
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Genetic association to the amyloid plaque associated protein gene COL25A1 in Alzheimer's disease
- 2010
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In: Neurobiology of Aging. - Fayetteville, N.Y. : Ankho International. - 0197-4580 .- 1558-1497. ; 31:3, s. 409-415
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Journal article (peer-reviewed)abstract
- The COL25A1 gene, located in 4q25, encodes the CLAC protein, which has been implicated in Alzheimer's disease (AD) pathogenesis. CLAC was originally identified in amyloid preparations from AD brain and has been shown to be associated with amyloid plaques, inhibition of Abeta-fibril elongation and increased protease resistance of Abeta-fibrils through direct binding to Abeta. These biochemical data as well as the genomic location of the COL25A1 gene in chromosome 4q25 where we previously have reported a weak linkage-signal in Swedish AD families encouraged us to perform a case-control association study of two LD blocks in COL25A1 using 817 AD cases and 364 controls. The LD blocks cover a putative Abeta-binding motif and the variable 3' end of the gene. The analyses indicated association to three of eight analysed SNPs. We found further support for the association by replication in a Swedish population-based longitudinal sample set (n=926). Thus, in addition to the biochemical data, there is now genetic evidence of association between COL25A1 and risk for Alzheimer's disease.
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