Objectives
To examine sex differences in prevalent comorbidity and frailty across age and European regions.
Methods
This is a cross-sectional study based on 113,299 Europeans aged 50+ participating ...in the Survey of Health, Ageing and Retirement in Europe from 2004–2005 to 2015. Sex differences in the Comorbidity Index and the Frailty Phenotype were investigated using ordinal logistic regressions.
Results
European women had generally higher odds of prevalent comorbidity (OR 1.11, 95% CI 1.07–1.15) and frailty (OR 1.56, 95% CI 1.51–1.62). Sex differences increased with advancing age. No overall sex difference in comorbidity was found in Western Europe, but women had more comorbidity than men in Eastern (OR 1.30, 95% CI 1.18–1.44), Southern (OR 1.23, 95% CI 1.15–1.30), and Northern (OR 1.08, 95% CI 1.01–1.16) Europe. Women were frailer than men in all regions, with the largest sex difference in Southern Europe (OR 1.84, 95% CI 1.72–1.96).
Conclusions
European women are frailer and have slightly more comorbidity than European men lending support for the male–female health survival paradox.
Postoperative cognitive dysfunction is common, but it remains unclear whether there are long-term adverse cognitive effects of surgery combined with anesthesia. The authors examined the association ...between exposure to surgery and level of cognitive functioning in a sample of 8,503 middle-aged and elderly twins.
Results from five cognitive tests were compared in twins exposed to surgery, classified as major, minor, hip and knee replacement, or other, with those of a reference group without surgery using linear regression adjusted for sex and age. Genetic and shared environmental confounding was addressed in intrapair analyses of 87 monozygotic and 124 dizygotic same-sexed twin pairs in whom one had a history of major surgery and the other did not.
Statistically significantly lower composite cognitive score was found in twins with at least one major surgery compared with the reference group (mean difference, -0.27; 95% CI, -0.48 to -0.06), corresponding to one tenth of an SD, that is, a negligible effect size. In the intrapair analysis, the surgery-exposed co-twin had the lower cognitive score in 49% (95% CI, 42 to 56%) of the pairs. None of the other groups differed from the reference group except the knee and hip replacement group that tended to have higher cognitive scores (mean difference, 0.35; 95% CI, -0.18 to 0.87).
A history of major surgery was associated with a negligibly lower level of cognitive functioning. The supplementary analyses suggest that preoperative cognitive functioning and underlying diseases were more important for cognitive functioning in mid- and late life than surgery and anesthesia.
Weighing risks and benefits of postmenopausal hormone therapy (HT) has proven a balancing act. We aimed to investigate the association between HT and mortality before and after the 2002 publication ...from the Women's Health Initiative (WHI) study. This publication found that the risk of using HT outweighted the benefits, and thus it caused a marked reduction in systemic HT user prevalence. The 2002 WHI publication may also have caused a change in the subsequent HT user profile, as HT is no longer recommended in the prevention of chronic diseases. This cohort study included two populations followed from 1995: A 5% random sample of female singletons from the Danish general population (n = 52,388) and a sample of Danish female twins (n = 15,261). HT use was evaluated in 1995, 2000, 2005, and 2010. The association between HT, education, and mortality was investigated and controlled for potential unobserved familial confounding in a within-pair analysis. Singletons aged 56-75 using systemic HT in 2000 had a lower mortality compared to non-users (hazard ratio (HR) 0.83, 95% confidence interval (CI) 0.78-0.89). In 2005, the mortality was like that of the background population for this age group (HR 1.02, 95% CI 0.94-1.11). Recently postmenopausal twins showed a similar tendency. Systemic HT users, who had switched to local HT by 2005, had a substantially lower mortality than non-users (HR ranging from 0.42 to 0.67 depending on age group). In conclusion, we found that the prevalence of systemic HT use declined after 2002, and systemic HT users' mortality changed from lower before 2002 to similar to that of the background population after 2002. This indicates that the healthiest users decided to either drop systemic HT or switcted to local HT, as recommendations changed following the WHI publication.
This review examines sex differences in health and survival, with a focus on the Nordic countries. There is a remarkable discrepancy between the health and survival of the sexes: men are physically ...stronger and have fewer disabilities, but have substantially higher mortality at all ages compared with women: the so-called male-female health-survival paradox. A number of proposed explanations for this paradox are rooted in biological, social, and psychological interpretations. It is likely to be due to multiple causes that include fundamental biological differences between the sexes such as genetic factors, immune system responses, hormones, and disease patterns. Behavioral differences such as risk-taking and reluctance to seek and comply with medical treatment may also play a role. Another consideration is that part of the difference may be due to methodological challenges, such as selective non-participation and under-reporting of health problems, and delayed seeking of treatment by men. The Nordic countries provide a unique opportunity for such studies, as they have good-quality data in their national health registers, which cover the whole population, and a long tradition of high participation rates in surveys.
Late-life loss of independence in daily living is a central concern for the aging individual and for society. The implications of increased survival to advanced age may be different at the population ...level than at the individual level. Here we used a longitudinal multi-assessment survey of the entire Danish 1905 cohort from 1998 to 2005 to assess the loss of physical and cognitive independence in the age range of 92 to 100 years. Multiple functional outcomes were studied, including independence, which was defined as being able to perform basic activities of daily living without assistance from other persons and having a MiniMental State Examination (MMSE) score of 23 or higher. In the aggregate, the 1905 cohort had only a modest decline in the proportion of independent individuals at the 4 assessments between age 92 and 100 years: 39%, 36%, 32%, and 33%, with a difference between first and last assessment of 6% 95% confidence interval (CI), -1-14%. For participants who survived until 2005, however, the prevalence of independence was reduced by more than a factor of 2, from 70% in 1998 to 33% in 2005 (difference, 37%; 95% CI, 28-46%). Similar results were obtained for the other functional outcomes. Analyses of missing data resulting from nonresponse and death suggest that the discrepancy between the population trajectory and the individual trajectory is caused by increased mortality among dependent individuals. For the individual, long life brings an increasing risk of loss of independence. For society, mortality reductions are not expected to result in exceptional levels of disability in cohorts of the very old.
Hypothyroidism has been linked with an increased risk of other morbidities, such as cardiovascular diseases and diabetes mellitus. However, the temporal relationship between these diseases and the ...diagnosis of hypothyroidism is not well illuminated. Such information may provide insight into causal relationships between hypothyroidism and other morbidities.
To investigate the type and extent of somatic morbidity before and after a diagnosis of hypothyroidism.
Observational cohort study. From official Danish health registers, 2822 hypothyroid singletons were identified and matched 1:4 with non-hypothyroid controls and observed over a mean period of 6 years. Frequency of different morbidities was obtained by person-to-person linking in the registers. Logistic and Cox regression models were used to assess the risk of morbidity before and after the diagnosis of hypothyroidism, respectively.
Prior to the diagnosis of hypothyroidism there was a significantly increased risk of being diagnosed with cardiovascular diseases (odds ratio (OR) 1.37; 95% confidence interval (CI): 1.19-1.58), lung diseases (OR 1.25; 95% CI: 1.13-1.39), diabetes mellitus (OR 1.92; 95% CI: 1.61-2.29), as well as malignant diseases (OR 1.24; 95% CI: 1.06-1.45). Following the diagnosis of hypothyroidism there was a significantly increased risk of being diagnosed with cardiovascular diseases (hazard ratio (HR) 1.36; 95% CI: 1.15-1.60); lung diseases (HR 1.51; 95% CI: 1.30-1.75); and diabetes mellitus (HR 1.40; 95% CI: 1.11-1.77).
Prior to the diagnosis of hypothyroidism there is an excess risk of being diagnosed with cardiovascular diseases, lung diseases, diabetes mellitus, and malignant diseases. Following the diagnosis of hypothyroidism we demonstrate an increased frequency of cardiovascular diseases, lung diseases, and diabetes mellitus.
Abstract
Background
As populations age, the possible consequences of increased frailty are a major concern for the health sector. Here, we investigate how life expectancy with and without frailty has ...changed during a 10–11-year-period across Europe.
Methods
The Sullivan method was used to investigate changes in life expectancy with and without frailty in 10 European countries. Frailty status (non-frail, pre-frail and frail) was determined by use of the Survey of Health, Ageing and Retirement in Europe Frailty Instrument (SHARE-FI). Data on frailty prevalence was obtained from 21 698 individuals in wave 1 (2004–05) and 38 859 individuals in wave 6 (2015) of the SHARE. Information on mortality was obtained from the Eurostat Database.
Results
In 2015, women aged 70 spent 25.0% (95% CI: 24.0–26.1) of their remaining life expectancy in a frail state, and the number for men was 11.5% (95% CI: 10.7–12.3). Southern Europeans spent 24.2% (95% CI: 22.9–25.4) of their remaining life expectancy in a frail state and the numbers for Central Europeans and Northern Europeans were 17.0% (95% CI: 16.0–17.9) and 12.2% (95% CI: 10.9–13.5), respectively. From 2004–05 to 2015, life expectancy increased by 1.1 years (from 15.3 to 16.4 years) for 70-year-old Europeans. Similarly, non-frail life expectancy increased by 1.1 years (95% CI: 0.8–1.4), whereas no significant changes in life expectancy in frail states were observed.
Conclusions
This study suggests that Europeans today spend more years in a non-frail state than Europeans did 10–11 years ago. Our findings reflect a considerable inequality by gender and region.
Summary
The accumulation of epigenetic changes was proposed to contribute to the age‐related increase in the risk of most common diseases. In this study on 230 monozygotic twin pairs (MZ pairs), aged ...18–89 years, we investigated the occurrence of epigenetic changes over the adult lifespan. Using mass spectrometry, we investigated variation in global (LINE1) DNA methylation and in DNA methylation at INS, KCNQ1OT1, IGF2, GNASAS, ABCA1, LEP, and CRH, candidate loci for common diseases. Except for KCNQ1OT1, interindividual variation in locus‐specific DNA methylation was larger in old individuals than in young individuals, ranging from 1.2‐fold larger at ABCA1 (P = 0.010) to 1.6‐fold larger at INS (P = 3.7 × 10−07). Similarly, there was more within‐MZ‐pair discordance in old as compared with young MZ pairs, except for GNASAS, ranging from an 8% increase in discordance each decade at CRH (P = 8.9 × 10−06) to a 16% increase each decade at LEP (P = 2.0 × 10−08). Still, old MZ pairs with strikingly similar DNA methylation were also observed at these loci. After 10‐year follow‐up in elderly twins, the variation in DNA methylation showed a similar pattern of change as observed cross‐sectionally. The age‐related increase in methylation variation was generally attributable to unique environmental factors, except for CRH, for which familial factors may play a more important role. In conclusion, sustained epigenetic differences arise from early adulthood to old age and contribute to an increasing discordance of MZ twins during aging.
Prostate cancer is thought to be the most heritable cancer, although little is known about how this genetic contribution varies across age.
To address this question, we undertook the world's largest ...prospective study in the Nordic Twin Study of Cancer cohort, including 18,680 monozygotic (MZ) and 30,054 dizygotic (DZ) same-sex male twin pairs. We incorporated time-to-event analyses to estimate the risk concordance and heritability while accounting for censoring and competing risks of death, essential sources of biases that have not been accounted for in previous twin studies modeling cancer risk and liability.
The cumulative risk of prostate cancer was similar to that of the background population. The cumulative risk for twins whose co-twin was diagnosed with prostate cancer was greater for MZ than for DZ twins across all ages. Among concordantly affected pairs, the time between diagnoses was significantly shorter for MZ than DZ pairs (median, 3.8 versus 6.5 years, respectively). Genetic differences contributed substantially to variation in both the risk and the liability heritability = 58% (95% confidence interval, 52%-63%) of developing prostate cancer. The relative contribution of genetic factors was constant across age through late life with substantial genetic heterogeneity even when diagnosis and screening procedures vary.
Results from the population-based twin cohort indicate a greater genetic contribution to the risk of developing prostate cancer when addressing sources of bias. The role of genetic factors is consistently high across age.
Findings affect the search for genetic and epigenetic markers and frame prevention efforts.
Hyperthyroidism has been linked with different morbidities, like atrial fibrillation, stroke and diabetes mellitus. However, our knowledge regarding the extent and temporal relation between ...hyperthyroidism and other diseases is fragmented. Here, we aimed at evaluating various morbidities before and after the diagnosis of hyperthyroidism.
Observational cohort study. From nationwide Danish health registers 2631 hyperthyroid singletons and 375 twin pairs discordant for hyperthyroidism were identified and followed for an average of 6 years (range 0-13). Data on the occurrence of cardiovascular diseases, lung diseases, diabetes mellitus, rheumatic diseases and malignant diseases was obtained by person-to-person record linkage with the National Danish Patient Register and/or the Danish National Prescription Registry (lung diseases and diabetes mellitus). Logistic and Cox regression models were used to assess the risk of morbidity before and after the diagnosis of hyperthyroidism, respectively. All Cox regression analyses were adjusted for the degree of co-morbidity preceding the diagnosis of hyperthyroidism, using the Charlson score.
Hyperthyroid individuals had a significantly higher risk of being diagnosed with cardiovascular diseases (odds ratio (OR) 1.65; 95% confidence interval (CI): 1.45-1.87), lung diseases (OR 1.53; 95% CI: 1.29-1.60), and diabetes mellitus (OR 1.43, 95% CI: 1.20-1.72), but not with malignant diseases (OR 1.16, 95% CI: 0.99-1.36) prior to the diagnosis of hyperthyroidism. After the diagnosis of hyperthyroidism, subjects had a significantly higher risk of being diagnosed with cardiovascular diseases (hazard ratio (HR) 1.34; 95% CI: 1.15-1.56), lung diseases (HR 1.28; 95% CI: 1.10-1.49), and diabetes mellitus (HR 1.46; 95% CI: 1.16-1.84), but not with rheumatic diseases (HR 1.39, 95% CI: 0.92-2.09) or malignant diseases (HR 1.18, 95% CI 0.97-1.42).
We demonstrate a significantly increased burden of morbidity, both before and after the diagnosis of hyperthyroidism.