Living longer than expected : protective and risk factors related to human longevity

The scientific community has become increasingly interested in understanding what lies behind the continuing extension of the human lifespan. The main aim of this thesis was to better understand the association between health status, lifestyle, genetic factors and survival in advanced age. Data used in the 4 studies are gathered from the Kungsholmen Project, a longitudinal population-based study on 75 year and older participants living in Stockholm, Sweden. Study I. Dementia, cardiovascular disease (CVD), and cancer were associated with a 2- to 3-fold increased rate of all-cause mortality. The mean survival times after incident diagnosis were 4.1 years for dementia, 4.2 years for CVD, and 2.2 years for cancer. A total of 3.4 potential years of life were lost because of dementia, 3.6 of CVD, and 4.4 because of cancer. Women aged 75 to 84 years lived longer than coetaneous men after incident diagnosis of dementia because they spent 1.6 years longer than men in the severe stage of the disease. Study II. Findings suggest that APOE alleles play different roles in the survival of elderly women and men. The mortality rate was 40% lower among women, but not men, who carried the ε2 allele, compared with the ε3ε3 carriers. The ε4 allele was associated with a 50% higher rate of death only among men. Dementia, not ischemic heart and cerebrovascular diseases, accounted for the majority of the increased mortality rate in those with the ε4 allele. Study III. Maintaining a healthy lifestyle and a rich social network was positively associated with survival even among people aged 75 years and older. People who reported being physically active a minimum of once a month lived about 2 years longer than those who did not. Non-smokers 75 years and older who participated in at least 1 leisure activity a month and had good social support lived about 5 years longer than inactive smokers with poor social support. These association, although attenuated, were also found in individuals aged 85 years and older and those with chronic diseases. Study IV. Genetic risk factors were relevant for survival after age 75. Variations in 4 different genes (APOC1, APOE, IDE, and PI3K) were associated with 12–20% increased rate of mortality. However, participants with at least 1 risk allele and a healthy lifestyle had about 70% lower rate of death than those with no risk allele and an unhealthy lifestyle. Those with no risk alleles and a healthy lifestyle had 80% lower mortality rate and 6 years longer median lifespan than people with at least 1 risk allele and unhealthy lifestyle. In conclusion, survival after 75 years of age was associated with health status, lifestyle, genetic factors, and a combination of those factors. These findings may help prognostic evaluation of the duration of specific diseases. They underscore the malignant nature of dementia as a result of the long period individuals lived with the severe disease stages, especially for women. These findings also suggest that the benefit of a healthy lifestyle, healthy behavior, and social support probably last a lifetime. Moreover, allelic variations in genes were associated with higher mortality rate, but the combined effect of genetic-environmental joint exposures may lead to the attenuation of the mortality rate, indicating that people with genetic susceptibility may reduce their initial mortality rate by modifying their lifestyle. Therefore, efforts to encourage smoking cessation, physical activity, and social engagement should be continued long into late life

personality and survival in older age the role of lifestyle behaviors and health status

Objective We intended to assess the relationship between personality and survival in an older population and to explore the role of lifestyle behaviors and health status as potential mediators. Design Population-based cohort study. Setting Swedish National Study of Aging and Care in Kungsholmen, Sweden. Participants 2,298 adults aged 60 or more years, without dementia or depression, followed for 11 years. Measurements Personality (extraversion, neuroticism, and openness) was assessed with a shortened version of the NEO-Five Factor Inventory. We tested whether personality affected mortality and examined the potential mediating effect of health status (body mass index, number of chronic diseases, impairment in instrumental activities of daily living, and C-reactive protein) and lifestyle behaviors (leisure activities, social network, smoking, and alcohol consumption). Results Over 11 years of follow-up, higher levels of extraversion were associated with a 14% reduction in mortality. Examination of different combinations of personality traits showed that independent of levels of neuroticism and openness, high extraversion were associated with up to 65% lower mortality. Decomposing the effect of extraversion on mortality, we found that the majority (44%) of the beneficial effect was mediated by healthy lifestyle behaviors. Health status accounted for 5% of the association. Conclusions Extroverted people, who are characterized by higher optimism and high self-efficacy, are prone to healthier behaviors and better health, which may result in longer survival. These results highlight the importance of a healthy lifestyle in survival

Peak expiratory flow, walking speed and survival in older adults: An 18-year longitudinal population-based study

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Choosing Wisely? Measuring the Burden of Medications in Older Adults near the End of Life: Nationwide, Longitudinal Cohort Study

Abstract Background The burden of medications near the end of life has recently come under scrutiny, because several studies suggested that people with life-limiting illness receive potentially futile treatments. Methods We identified 511,843 older adults (>65 years) who died in Sweden between 2007 and 2013 and reconstructed their drug prescription history for each of the last 12 months of life through the Swedish Prescribed Drug Register. Decedents' characteristics at time of death were assessed through record linkage with the National Patient Register, the Social Services Register, and the Swedish Education Register. Results Over the course of the final year before death, the proportion of individuals exposed to ≥10 different drugs rose from 30.3% to 47.2% ( P Conclusion Polypharmacy increases throughout the last year of life of older adults, fueled not only by symptomatic medications but also by long-term preventive treatments of questionable benefit. Clinical guidelines are needed to support physicians in their decision to continue or discontinue medications near the end of life

Multimorbidity burden and dementia risk in older adults : The role of inflammation and genetics

Funding: Swedish National study on Aging and Care; Ministry of Health and Social Affairs; Swedish Research Council, Grant/Award Number: 2016-00981; Swedish Research Council for Health,Working Life andWelfare, Grant/Award Number: 2017-01764; Italian Ministry of Health, Grant/Award Number: PE-2016-02364885We investigate dementia risk in older adults with different disease patterns and explore the role of inflammation and apolipoprotein E (APOE) genotype. A total of 2,478 dementia-free participants with two or more chronic diseases (ie, multimorbidity) part of the Swedish National study on Aging and Care in Kungsholmen (SNAC-K) were grouped according to their multimorbidity patterns and followed to detect clinical dementia. The potential modifier effect of C-reactive protein (CRP) and apolipoprotein E (APOE) genotype was tested through stratified analyses. People with neuropsychiatric, cardiovascular, and sensory impairment/cancer multimorbidity had increased hazards for dementia compared to the unspecific (Hazard ration (HR) 1.66, 95% confidence interval [CI] 1.13-2.42; 1.61, 95% CI 1.17-2.29; 1.32, 95% CI 1.10-1.71, respectively). Despite the lack of statistically significant interaction, high CRP increased dementia risk within these patterns, and being APOE ε4 carriers heightened dementia risk for neuropsychiatric and cardiovascular multimorbidity. Individuals with neuropsychiatric, cardiovascular, and sensory impairment/cancer patterns are at increased risk for dementia and APOE ε4, and inflammation may further increase the risk. Identifying such high-risk groups might allow tailored interventions for dementia prevention

Long-term exposure to transportation noise and risk of incident stroke:A pooled study of nine scandinavian cohorts

BACKGROUND: Transportation noise is increasingly acknowledged as a cardiovascular risk factor, but the evidence base for an association with stroke is sparse. OBJECTIVE: We aimed to investigate the association between transportation noise and stroke incidence in a large Scandinavian population. METHODS: We harmonized and pooled data from nine Scandinavian cohorts (seven Swedish, two Danish), totaling 135,951 participants. We identified residential address history and estimated road, railway, and aircraft noise for all addresses. Information on stroke incidence was acquired through link-age to national patient and mortality registries. We analyzed data using Cox proportional hazards models, including socioeconomic and lifestyle con-founders, and air pollution. RESULTS: During follow-up (median = 19:5 y), 11,056 stroke cases were identified. Road traffic noise (Lden ) was associated with risk of stroke, with a hazard ratio (HR) of 1.06 [95% confidence interval (CI): 1.03, 1.08] per 10-dB higher 5-y mean time-weighted exposure in analyses adjusted for indi-vidual-and area-level socioeconomic covariates. The association was approximately linear and persisted after adjustment for air pollution [particulate matter (PM) with an aerodynamic diameter of ≤2:5 lm (PM2:5 ) and NO2 ]. Stroke was associated with moderate levels of 5-y aircraft noise exposure (40–50 vs. ≤40 dB) (HR = 1:12; 95% CI: 0.99, 1.27), but not with higher exposure (≥50 dB, HR = 0:94; 95% CI: 0.79, 1.11). Railway noise was not associated with stroke. DISCUSSION: In this pooled study, road traffic noise was associated with a higher risk of stroke. This finding supports road traffic noise as an important cardiovascular risk factor that should be included when estimating the burden of disease due to traffic noise. https://doi.org/10.1289/EHP8949

Particulate matter air pollution components and incidence of cancers of the stomach and the upper aerodigestive tract in the European Study of Cohorts of Air Pollution Effects (ESCAPE)

© 2020 Elsevier Ltd. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence http://creativecommons.org/licenses/by-nc-nd/4.0/.Introduction: Previous analysis from the large European multicentre ESCAPE study showed an association of ambient particulate matter <2.5 μm (PM2.5) air pollution exposure at residence with the incidence of gastric cancer. It is unclear which components of PM are most relevant for gastric and also upper aerodigestive tract (UADT) cancer and some of them may not be strongly correlated with PM mass. We evaluated the association between long-term exposure to elemental components of PM2.5 and PM10 and gastric and UADT cancer incidence in European adults. Methods: Baseline addresses of individuals were geocoded and exposure was assessed by land-use regression models for copper (Cu), iron (Fe) and zinc (Zn) representing non-tailpipe traffic emissions; sulphur (S) indicating long-range transport; nickel (Ni) and vanadium (V) for mixed oil-burning and industry; silicon (Si) for crustal material and potassium (K) for biomass burning. Cox regression models with adjustment for potential confounders were used for cohort-specific analyses. Combined estimates were determined with random effects meta-analyses. Results: Ten cohorts in six countries contributed data on 227,044 individuals with an average follow-up of 14.9 years with 633 incident cases of gastric cancer and 763 of UADT cancer. The combined hazard ratio (HR) for an increase of 200 ng/m3 of PM2.5_S was 1.92 (95%-confidence interval (95%-CI) 1.13;3.27) for gastric cancer, with no indication of heterogeneity between cohorts (I2 = 0%), and 1.63 (95%-CI 0.88;3.01) for PM2.5_Zn (I2 = 70%). For the other elements in PM2.5 and all elements in PM10 including PM10_S, non-significant HRs between 0.78 and 1.21 with mostly wide CIs were seen. No association was found between any of the elements and UADT cancer. The HR for PM2.5_S and gastric cancer was robust to adjustment for additional factors, including diet, and restriction to study participants with stable addresses over follow-up resulted in slightly higher effect estimates with a decrease in precision. In a two-pollutant model, the effect estimate for total PM2.5 decreased whereas that for PM2.5_S was robust. Conclusion: This large multicentre cohort study shows a robust association between gastric cancer and long-term exposure to PM2.5_S but not PM10_S, suggesting that S in PM2.5 or correlated air pollutants may contribute to the risk of gastric cancer.Peer reviewedFinal Accepted Versio