Summary Background The oldest-old (those aged ≥80 years) are the most rapidly growing age group globally, and are most in need of health care and assistance. We aimed to assess changes in mortality, ...disability in activities of daily living, and physical and cognitive functioning among oldest-old individuals between 1998 and 2008. Methods We used data from the Chinese Longitudinal Healthy Longevity Study. Three pairs of cohorts aged 80–89 years, 90–99 years, and 100–105 years (in total, 19 528 oldest-old participants) were examined; the two cohorts in each pair were born 10 years apart, with the same age at the time of the assessment in the 1998 and 2008 surveys. Four health outcomes were investigated: annual death rate, Activities of Daily Living (ADL), physical performance in three tests and cognitive function measured by Mini-Mental State Examination (MMSE). We used different tests and multivariate regression analyses to examine the cohort differences. Findings Controlling for various confounding factors, we noted that annual mortality among oldest-old individuals was substantially reduced between 0·2% and 1·3% in 1998–2008 compared with individuals of the same age born 10 years previously, and that disability according to activities of daily living had significantly reduced annually between 0·8% and 2·8%. However, cognitive impairment in the later cohorts increased annually between 0·7% and 2·2% and objective physical performance capacity (standing up from a chair, picking up a book from the floor, and turning around 360°) decreased anually between 0·4% and 3·8%. We also noted that female mortality was substantially lower than male mortality among the oldest-old, but that women's functional capacities in activities of daily living, cognition, and physical performance were worse than their male counterparts. Interpretation Advances in medications, lifestyle, and socioeconomics might compress activities of daily living disability, that is, benefits of success, but lifespan extension might expand disability of physical and cognitive functioning as more frail, elderly individuals survive with health problems, that is, costs of success. Funding National Natural Science Foundation of China, National Institute on Aging/National Institutes of Health, United Nations Funds for Population Activities.
Twin studies have provided evidence that both genetic and environmental factors contribute to schizophrenia (SZ) risk. Heritability estimates of SZ in twin samples have varied methodologically. This ...study provides updated heritability estimates based on nationwide twin data and an improved statistical methodology.
Combining two nationwide registers, the Danish Twin Register and the Danish Psychiatric Research Register, we identified a sample of twins born between 1951 and 2000 (N = 31,524 twin pairs). Twins were followed until June 1, 2011. Liability threshold models adjusting for censoring with inverse probability weighting were used to estimate probandwise concordance rates and heritability of the diagnoses of SZ and SZ spectrum disorders.
The probandwise concordance rate of SZ is 33% in monozygotic twins and 7% in dizygotic twins. We estimated the heritability of SZ to be 79%. When expanding illness outcome to include SZ spectrum disorders, the heritability estimate was almost similar (73%).
The key strength of this study is the application of a novel statistical method accounting for censoring in the follow-up period to a nationwide twin sample. The estimated 79% heritability of SZ is congruent with previous reports and indicates a substantial genetic risk. The high genetic risk also applies to a broader phenotype of SZ spectrum disorders. The low concordance rate of 33% in monozygotic twins demonstrates that illness vulnerability is not solely indicated by genetic factors.
Summary If the pace of increase in life expectancy in developed countries over the past two centuries continues through the 21st century, most babies born since 2000 in France, Germany, Italy, the ...UK, the USA, Canada, Japan, and other countries with long life expectancies will celebrate their 100th birthdays. Although trends differ between countries, populations of nearly all such countries are ageing as a result of low fertility, low immigration, and long lives. A key question is: are increases in life expectancy accompanied by a concurrent postponement of functional limitations and disability? The answer is still open, but research suggests that ageing processes are modifiable and that people are living longer without severe disability. This finding, together with technological and medical development and redistribution of work, will be important for our chances to meet the challenges of ageing populations.
Summary Background A rapidly increasing proportion of people in high-income countries are surviving into their tenth decade. Concern is widespread that the basis for this development is the survival ...of frail and disabled elderly people into very old age. To investigate this issue, we compared the cognitive and physical functioning of two cohorts of Danish nonagenarians, born 10 years apart. Methods People in the first cohort were born in 1905 and assessed at age 93 years (n=2262); those in the second cohort were born in 1915 and assessed at age 95 years (n=1584). All cohort members were eligible irrespective of type of residence. Both cohorts were assessed by surveys that used the same design and assessment instrument, and had almost identical response rates (63%). Cognitive functioning was assessed by mini-mental state examination and a composite of five cognitive tests that are sensitive to age-related changes. Physical functioning was assessed by an activities of daily living score and by physical performance tests (grip strength, chair stand, and gait speed). Findings The chance of surviving from birth to age 93 years was 28% higher in the 1915 cohort than in the 1905 cohort (6·50% vs 5·06%), and the chance of reaching 95 years was 32% higher in 1915 cohort (3·93% vs 2·98%). The 1915 cohort scored significantly better on the mini-mental state examination than did the 1905 cohort (22·8 SD 5·6 vs 21·4 6·0; p<0·0001), with a substantially higher proportion of participants obtaining maximum scores (28–30 points; 277 23% vs 235 13%; p<0·0001). Similarly, the cognitive composite score was significantly better in the 1915 than in the 1905 cohort (0·49 SD 3·6 vs 0·01 SD 3·6; p=0·0003). The cohorts did not differ consistently in the physical performance tests, but the 1915 cohort had significantly better activities of daily living scores than did the 1905 cohort (2·0 SD 0·8 vs 1·8 0·7; p<0·0001). Interpretation Despite being 2 years older at assessment, the 1915 cohort scored significantly better than the 1905 cohort on both the cognitive tests and the activities of daily living score, which suggests that more people are living to older ages with better overall functioning. Funding Danish National Research Foundation; US National Institutes of Health—National Institute on Aging; Danish Agency for Science, Technology and Innovation; VELUX Foundation.
Women in almost all modern populations live longer than men. Research to date provides evidence for both biological and social factors influencing this gender gap. Conditions when both men and women ...experience extremely high levels of mortality risk are unexplored sources of information. We investigate the survival of both sexes in seven populations under extreme conditions from famines, epidemics, and slavery. Women survived better than men: In all populations, they had lower mortality across almost all ages, and, with the exception of one slave population, they lived longer on average than men. Gender differences in infant mortality contributed the most to the gender gap in life expectancy, indicating that newborn girls were able to survive extreme mortality hazards better than newborn boys. Our results confirm the ubiquity of a female survival advantage even when mortality is extraordinarily high. The hypothesis that the survival advantage of women has fundamental biological underpinnings is supported by the fact that under very harsh conditions females survive better than males even at infant ages when behavioral and social differences may be minimal or favor males. Our findings also indicate that the female advantage differs across environments and is modulated by social factors.
Abstract
Background and Objectives
The present cross-sectional study examines gender differences in three major health measures among older adults in India and in China, and investigates whether ...these differences can be explained by major sociodemographic and health risk characteristics.
Research Design and Methods
The study included 7,150 individuals in India and 13,367 individuals in China aged 50-plus who participated in the WHO Study on Global AGEing and Adult Health in 2007–2010. Logistic regression models for self-reported health (SRH) and ordinary least square regression models for grip strength and cognitive function were used to investigate gender differences in health.
Results
A consistent female disadvantage was found in India and in China for all three health measures. Compared to their male counterparts, women in the Indian and the Chinese samples had, respectively, 38% (95% confidence interval CI: 1.22, 1.56) and 36% (95% CI: 1.25, 1.48) higher risk of reporting poor SRH, 9.56 kg (95% CI: 9.91, 9.22) and 11.95 kg (95% CI: 12.29, 11.62) lower grip strength, and 3.64 (95% CI: 3.96, 3.32) and 1.99 (95% CI: 2.28, 1.71) lower cognitive scores. The magnitude of the female disadvantage in poor SRH and in grip strength changed very little when adjustments were made for marital status, education, place of residence, smoking status, height, and number of chronic conditions; but these characteristics accounted for about 50% of the gender gap in cognitive function.
Discussion and Implications
In these study populations, major sociodemographic and health risk characteristics accounted for very small parts of the gender differences in health, except in cognition.
Estimates of familial cancer risk from population-based studies are essential components of cancer risk prediction.
To estimate familial risk and heritability of cancer types in a large twin cohort.
...Prospective study of 80,309 monozygotic and 123,382 same-sex dizygotic twin individuals (N = 203,691) within the population-based registers of Denmark, Finland, Norway, and Sweden. Twins were followed up a median of 32 years between 1943 and 2010. There were 50,990 individuals who died of any cause, and 3804 who emigrated and were lost to follow-up.
Shared environmental and heritable risk factors among pairs of twins.
The main outcome was incident cancer. Time-to-event analyses were used to estimate familial risk (risk of cancer in an individual given a twin's development of cancer) and heritability (proportion of variance in cancer risk due to interindividual genetic differences) with follow-up via cancer registries. Statistical models adjusted for age and follow-up time, and accounted for censoring and competing risk of death.
A total of 27,156 incident cancers were diagnosed in 23,980 individuals, translating to a cumulative incidence of 32%. Cancer was diagnosed in both twins among 1383 monozygotic (2766 individuals) and 1933 dizygotic (2866 individuals) pairs. Of these, 38% of monozygotic and 26% of dizygotic pairs were diagnosed with the same cancer type. There was an excess cancer risk in twins whose co-twin was diagnosed with cancer, with estimated cumulative risks that were an absolute 5% (95% CI, 4%-6%) higher in dizygotic (37%; 95% CI, 36%-38%) and an absolute 14% (95% CI, 12%-16%) higher in monozygotic twins (46%; 95% CI, 44%-48%) whose twin also developed cancer compared with the cumulative risk in the overall cohort (32%). For most cancer types, there were significant familial risks and the cumulative risks were higher in monozygotic than dizygotic twins. Heritability of cancer overall was 33% (95% CI, 30%-37%). Significant heritability was observed for the cancer types of skin melanoma (58%; 95% CI, 43%-73%), prostate (57%; 95% CI, 51%-63%), nonmelanoma skin (43%; 95% CI, 26%-59%), ovary (39%; 95% CI, 23%-55%), kidney (38%; 95% CI, 21%-55%), breast (31%; 95% CI, 11%-51%), and corpus uteri (27%; 95% CI, 11%-43%).
In this long-term follow-up study among Nordic twins, there was significant excess familial risk for cancer overall and for specific types of cancer, including prostate, melanoma, breast, ovary, and uterus. This information about hereditary risks of cancers may be helpful in patient education and cancer risk counseling.
Background The potential association between level of education and age-related cognitive decline remains an open question, partly because of a lack of studies including large subsamples with low ...education and follow-up intervals covering a substantial part of the adult lifespan. Objectives To examine cognitive decline assessed by a comprehensive clinical test of intelligence over a 35-year period of follow-up from ages 50 to 85 and to analyze the effect of education on trajectories of cognitive decline, including the effects of selective attrition. Methods A longitudinal cohort study with a 35-year follow-up of community dwelling members of the Glostrup 1914 cohort. The study sample comprised 697 men and women at the 50-year baseline assessment and additional participants recruited at later follow-ups. Verbal, Performance, and Full Scale IQs were assessed using the Wechsler Adult Intelligence Scale at ages 50, 60, 70, 80, and 85. To be able to track cognitive changes between successive WAIS assessments, all IQs were based on the Danish 50-year norms. Information on school education was self-reported. The association between education and cognitive decline over time was examined in growth curve models. Selective attrition was investigated in subsamples of participants who dropped out at early or later follow-ups. Results The trajectories for Verbal, Performance, and Full Scale IQ showed higher initial cognitive performance, but also revealed steeper decline among participants with a formal school exam compared to participants without a formal exam. Verbal IQ showed the largest difference in level between the two educational groups, whereas the interaction between education and age was stronger for Performance IQ than for Verbal IQ. In spite of the difference in trajectories, higher mean IQ was observed among participants with a formal school exam compared to those without across all ages, including the 85-year follow-up. Further analyses revealed that early dropout was associated with steeper decline, but that this effect was unrelated to education. Conclusion Comprehensive cognitive assessment over a 35-year period suggests that higher education is associated with steeper decline in IQ, but also higher mean IQ at all follow-ups. These findings are unlikely to reflect regression towards the mean, other characteristics of the employed test battery or associations between educational level and study dropout.
Mutations in the epigenetic modifier TET2 are frequent in myeloid malignancies and clonal hematopoiesis of indeterminate potential (CHIP) and clonal cytopenia of undetermined significance (CCUS). ...Here, we investigate associations between TET2 mutations and DNA methylation in whole blood in 305 elderly twins, 15 patients with CCUS and 18 healthy controls. We find that TET2 mutations are associated with DNA hypermethylation at enhancer sites in whole blood in CHIP and in both granulocytes and mononuclear cells in CCUS. These hypermethylated sites are associated with leukocyte function and immune response and ETS-related and C/EBP-related transcription factor motifs. While the majority of TET2-associated hypermethylation sites are shared between CHIP and in AML, we find a set of AML-specific hypermethylated loci at active enhancer elements in hematopoietic stem cells. In summary, we show that TET2 mutations is associated with hypermethylated enhancers involved in myeloid differentiation in both CHIP, CCUS and AML patients.
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•Autoimmune hepatitis accumulates in families.•Only first-degree relatives are at increased risk of autoimmune hepatitis.•The absolute risk of autoimmune hepatitis in family members ...is very low.
It is widely believed that autoimmune hepatitis accumulates in families, but the degree of familial clustering has not been clarified. We conducted a population-based study on the family occurrence of autoimmune hepatitis.
Through Danish nationwide registries we identified 8,582 first-degree and 9,230 second-degree relatives of index patients diagnosed with autoimmune hepatitis in 1994–2015; and 64 co-twins of index patients diagnosed with autoimmune hepatitis in 1977–2011. For first- and second-degree relatives we calculated the sex- and age-adjusted standardized incidence ratio of autoimmune hepatitis relative to the general population, and we calculated the cumulative risk, i.e. the cumulative incidence, of developing autoimmune hepatitis from the time of the index patient’s diagnosis. For co-twins, we estimated the standardized incidence ratio and the concordance rate of autoimmune hepatitis.
In first-degree relatives, there were six incident autoimmune hepatitis diagnoses during 64,020 years of follow-up: the standardized incidence ratio was 4.9 (95% CI 1.8–10.7), and the 10-year cumulative risk was 0.10% (95% CI 0.04–0.23). In the second-degree relatives, there were no incident autoimmune hepatitis diagnoses (expected number assuming incidence rate as in the Danish general population = 0.8). In the co-twins, there was one incident autoimmune hepatitis diagnosis during 1,112 years of follow-up, and the standardized incidence ratio was 53.9 (95% CI 1.4–300.4). The probandwise concordance rate, a measure of heritability, was higher in monozygotic than in dizygotic twins (8.7% 95% CI 1.1–28.0 vs. 0%).
This nationwide study indicates that only first-degree relatives of index patients with autoimmune hepatitis are at increased risk of autoimmune hepatitis from the time of the index patient’s diagnosis, but the absolute risk is very low.
Autoimmune hepatitis is a chronic liver disease caused by a dysfunctional immune system. It is widely believed that autoimmune hepatitis accumulates in families. We studied the family members of patients with autoimmune hepatitis from the entire Danish population. We found that autoimmune hepatitis does accumulate in families, but the risk of autoimmune hepatitis in the family members is very low.
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