Background The mortality rates of older people changes with the seasons. However, it has not been properly investigated whether the seasons affect medical care expenditure (MCE) and... Show moreBackground The mortality rates of older people changes with the seasons. However, it has not been properly investigated whether the seasons affect medical care expenditure (MCE) and institutionalization. Seasonal variation in MCE is plausible, as MCE rises exponentially before death. It is therefore important to investigate the impact of the seasons on MCE both mediated and unmediated by mortality. Methods Data on mortality, MCE and institutionalization from people aged 65 and older in a region in the Netherlands from July 2007 through 2010 were retrieved from a regional health care insurer and were linked with data from the Netherlands Institute for Social Research, and Statistics Netherlands (n = 61,495). The Seasonal and Trend decomposition using Loess (STL) method was used to divide mortality rates, MCE, and institutionalization rates into a long-term trend, seasonal variation, and remaining variation. For every season we calculated the 95% confidence interval compared to the long-term trend using Welch’s t-test. Results The mortality rates of older people differ significantly between the seasons, and are 21% higher in the winter compared to the summer. MCE rises with 13% from the summer to the winter; this seasonal difference is higher for the non-deceased than for the deceased group (14% vs. 6%). Seasonal variation in mortality is more pronounced in men and people in residential care. Seasonal variation in MCE is more pronounced in women. Institutionalization rates are significantly higher in the winter, but the other seasons show no significant impact.Conclusions Seasonal changes affect mortality and the level of MCE of older people; institutionalization rates peak in the winter. Seasonal variation in MCE exists independently from patterns in mortality. Seasonal variation in mortality is similar for both institutionalized and communitydwelling elderly. Policy-makers, epidemiologists and health economists are urged to acknowledge and include the impact of the seasons in future policy and research. Show less
Koopman, Jacob J.E.; Rozing, Maarten P.; Kramer, Anneke; Abad, José M.; Finne, Patrik; Heaf, James G.; ... ; Westendorp, Rudi G.J. 2015
The rate of senescence can be inferred from the acceleration by which mortality rates increase over age. Such a senescence rate is generally estimated from parameters of a mathematical model fitted... Show moreThe rate of senescence can be inferred from the acceleration by which mortality rates increase over age. Such a senescence rate is generally estimated from parameters of a mathematical model fitted to these mortality rates. However, such models have limitations and underlying assumptions. Notably, they do not fit mortality rates at young and old ages. Therefore, we developed a method to calculate senescence rates from the acceleration of mortality directly without modeling the mortality rates. We applied the different methods to age group–specific mortality data from the European Renal Association—European Dialysis and Transplant Association Registry, including patients with end-stage renal disease on dialysis, who are known to suffer from increased senescence rates (n = 302,455), and patients with a functioning kidney transplant (n = 74,490). From age 20 to 70, senescence rates were comparable when calculated with or without a model. However, when using non-modeled mortality rates, senescence rates were yielded at young and old ages that remained concealed when using modeled mortality rates. At young ages senescence rates were negative, while senescence rates declined at old ages. In conclusion, the rate of senescence can be calculated directly from non-modeled mortality rates, overcoming the disadvantages of an indirect estimation based on modeled mortality rates. Show less
Kaptijn, Ralf; Thomese, Fleur; Liefbroer, Aart C.; Poppel, Frans van; Bodegom, David van; Westendorp, Rudi G.J. 2015
Several hypotheses have been put forward to explain the relationship between women’s fertility and their post-reproductive longevity. In this study, we focus on the disposable soma theory, which... Show moreSeveral hypotheses have been put forward to explain the relationship between women’s fertility and their post-reproductive longevity. In this study, we focus on the disposable soma theory, which posits that a negative relationship between women’s fertility and longevity can be understood as an evolutionary trade-off between reproduction and survival. We examine the relationship between fertility and longevity during the epidemiological transition in the Netherlands. This period of rapid decline in mortality from infectious diseases offers a good opportunity to study the relationship between fertility and longevity, using registry data from 6,359 women born in The Netherlands between 1850 and 1910. We hypothesize that an initially negative relationship between women’s fertility and their longevity gradually turns less negative during the epidemiological transition, because of decreasing costs of higher parities. An initially inversed U-shaped association between fertility and longevity changes to zero during the epidemiological transition. This does suggest a diminishing environmental pressure on fertility. However, we find no evidence of an initial linear trade-off between fertility and post-reproductive survival. Show less
Koopman, Jacob J.E.; Bodegom, David van; Heemst, Diana van; Westendorp, Rudi G.J. 2015
Background: muscle strength measured as handgrip strength declines with increasing age and predicts mortality. While handgrip strength is determined by lifestyle through nutrition and physical... Show moreBackground: muscle strength measured as handgrip strength declines with increasing age and predicts mortality. While handgrip strength is determined by lifestyle through nutrition and physical activity, it has almost exclusively been studied in western populations with a sedentary lifestyle. This study aims to investigate the relation between handgrip strength, ageing and mortality in a population characterised by a predominance of malnutrition and manual labour. Design: a population-based longitudinal study. Setting: a traditional African rural population in Ghana. Subjects: nine hundred and twenty-three community-dwelling individuals aged 50 and older. Methods: demographic characteristics were registered. At baseline, height, body mass index (BMI) and handgrip strength were measured and compared with those in a western reference population. Survival of the participants was documented during a period of up to 2 years. Results: handgrip strength was dependent on age, sex, height and BMI. Compared with the western reference population, handgrip strength was lower due to a lower height and BMI but declined over age similarly. Risk of mortality was lower in participants having higher handgrip strength, with a hazard ratio of 0.94 per kg increase (P = 0.002). After adjustment for age, sex, tribe, socio-economic status, drinking water source, height and BMI, only handgrip strength remained predictive of mortality. Conclusion: in a traditional rural African population characterised by malnutrition and manual labour, handgrip strength declines over age and independently predicts mortality similar to western populations. Handgrip strength can be used as a universal marker of ageing. Show less
Rolden, Herbert J.A.; Bodegom, David van; Westendorp, Rudi G.J. 2014
Background: In ageing populations, informal care holds great potential to limit rising health care expenditure. The majority of informal care is delivered by spouses. The loss of informal care due... Show moreBackground: In ageing populations, informal care holds great potential to limit rising health care expenditure. The majority of informal care is delivered by spouses. The loss of informal care due to the death of the spouse could therefore increase expenditure levels for formal care. Objective: To investigate the impact of the death of the spouse on health care expenditure by older people through time. Additionally, to examine whether the impact differs between socio-demographic groups, and what health services are affectedmost. Design: Longitudinal data on health care expenditure (from July 2007 through 2010) from a regional Dutch health care insurer was matched with data on marital status (2004–2011) from the Central Bureau of Statistics. Linear mixed models with log transformed health care expenditure, generalized linear models and two-part models were used to retrieve standardized levels of monthly health care expenditure of 6,487 older widowed subjects in the 42 months before and after the loss of the spouse. Results: Mean monthly health care expenditure in married subjects was J502 in the 42 months before the death of the spouse, and expenditure levels rose by J239 (48%) in the 42 months after the death of the spouse. The increase in expenditure after the death of the spouse was highest for men (J319; 59%) and the oldest old (J553; 82%). Expenditure levels showed the highest increase for hospital and home care services (together J166). Conclusions: The loss of the spouse is associated with an increase in health care expenditure. The relatively high rise in long-term care expenses suggests that the loss of informal care is an important determinant of this rise. Show less
Rolden, Herbert J.A.; Bodegom, David van; Hout, Wilbert B. van den; Westendorp, Rudi G.J. 2014
Background As mortality is more and more concentrated at old age, it becomes critical to identify the determinants of old age mortality. It has counterintuitively been found that mortality rates at... Show moreBackground As mortality is more and more concentrated at old age, it becomes critical to identify the determinants of old age mortality. It has counterintuitively been found that mortality rates at all ages are higher during short-term increases in economic growth. Work-stress is found to be a contributing factor to this association, but cannot explain the association for the older, retired population. Methods Historical figures of gross domestic product (Angus Maddison) were compared with mortality rates (Human Mortality Database) of middle aged (40– 44 years) and older people (70–74 years) in 19 developed countries for the period 1950–2008. Regressions were performed on the de-trended data, accounting for autocorrelation and aggregated using random effects models. Results Most countries show pro-cyclical associations between the economy and mortality, especially with regard to male mortality rates. On average, for every 1% increase in gross domestic product, mortality increases with 0.36% for 70-year-old to 74-year-old men (p<0.001) and 0.38% for 40-year-old to 44-year-old men ( p<0.001). The effect for women is 0.18% for 70-year-olds to 74-year-olds ( p=0.012) and 0.15% for 40-year-olds to 44-year-olds ( p=0.118). Conclusions In developed countries, mortality rates increase during upward cycles in the economy, and decrease during downward cycles. This effect is similar for the older and middle-aged population. Traditional explanations as work-stress and traffic accidents cannot explain our findings. Lower levels of social support and informal care by the working population during good economic times can play an important role, but this remains to be formally investigated. Show less
Engelaer, Frouke M.; Koopman Jacob J.E.; Bodegom, David van; Eriksson, Ulrika K.; Westendorp, Rudi G.J. 2014
Background Many African countries experience a protracted epidemiologic transition, different from the classical transition in western societies. The factors driving this protracted transition are... Show moreBackground Many African countries experience a protracted epidemiologic transition, different from the classical transition in western societies. The factors driving this protracted transition are largely unknown. In northeast Ghana, we studied an ongoing epidemiologic transition and investigated the effects of socioeconomic status and drinking water source on the transition. Methods During a 9-year period, we followed a cohort of almost 30 000 individuals and collected information on mortality and fertility rates. In addition, using the standards set out by the WHO, we obtained the causes of death by verbal autopsy. Individuals were stratified according to their socioeconomic status and the households' use of an improved or unimproved drinking water source. Results Mortality rates decreased by −5.0% annually (p<0.001) and the main cause of death shifted from infectious to non-infectious diseases (p=0.014). General fertility rates and child-women ratios decreased annually by −12.7% (p<0.001) and −11.9% (p<0.001), respectively. There was no difference in the decline of mortality and fertility depending on socioeconomic status or drinking water source. Show less
Koopman, Jacob J.E.; Bodegom, David van; Westendorp, Rudi G.J.; Jukema, Johan Wouter 2014
Background: In western societies, atrial fibrillation is an increasingly common finding among the elderly. Established risk factors of atrial fibrillation include obesity, diabetes, hypertension,... Show moreBackground: In western societies, atrial fibrillation is an increasingly common finding among the elderly. Established risk factors of atrial fibrillation include obesity, diabetes, hypertension, and cardiovascular disease. Atrial fibrillation has almost exclusively been studied in western populations where these risk factors are widely present. Therefore, we studied the epidemiology of atrial fibrillation in a traditional African community. Methods: In rural Ghana, among 924 individuals aged 50 years and older, we recorded electrocardiograms to detect atrial fibrillation. As established risk factors, we documented waist circumference, body mass index (BMI), capillary glucose level, blood pressure, and electrocardiographic myocardial infarction. In addition, we determined circulating levels of interleukin-6 (IL6), a proinflammatory cytokine, and C-reactive protein (CRP), a marker of systemic inflammation. We compared the risk factors with reference data from the USA. Results: Atrial fibrillation was detected in only three cases, equalling 0.3% (95% CI 0.1–1.0%). Waist circumference, BMI, and capillary glucose levels were very low. Hypertension and myocardial infarction were uncommon. Circulating levels of IL6 were similar, but those of CRP were lower compared with the USA. Conclusion: Atrial fibrillation is very scarce in this traditional African community. Its low prevalence compared with western societies can be explained by the rareness of its established risk factors, which are closely related to lifestyle, and by possible unmeasured differences in other risk factors or genetic factors. Show less
Engelaer, Frouke M.; Bodegom, David van; Mangione, Julia N.A.; Eriksson, Ulrika K.; Westendorp, Rudi G.J. 2014
Steady growth in human life expectancy has been a key feature of the last century, with projected further increases likely to have enormous impacts on societies worldwide. Despite the significance... Show moreSteady growth in human life expectancy has been a key feature of the last century, with projected further increases likely to have enormous impacts on societies worldwide. Despite the significance of these changes, our understanding of the factors shaping this trend is incomplete. During most of the historical increase, by far, the major influence was progressive decline in early and midlife death rates because of the reduction in premature deaths, caused chiefly by infection. Recent decades have seen the emergence of a new driver of increasing longevity—declining mortality among those who are old already, pointing to greater malleability in human aging than had been foreseen. There is still debate, however, as to how much of this decrease in old age mortality is caused by a better early-life environment and how much is caused by improved conditions in late life. A unique resource exists in the case of Japan, where material circumstances for the general population were consistently adverse through the early decades of the 20th century but improved rapidly after 1950. Here, we compare the Japanese birth cohorts of 1900, 1910, and 1920 and follow their period and cohort mortality trends. The results show that cohorts with similar environments early in life have very different mortality trajectories in old age. This strengthens the expectation that preventive measures in later life can deliver great benefit, while not contradicting the importance of life course approaches, to improving health and well-being. Show less
Engelaer, Frouke M.; Bodegom, David van; Westendorp, Rudi G.J. 2012
Elder abuse has devastating consequences for older persons such as a poor quality of life, psychological distress, and loss of property and security. It is also associated with increased mortality... Show moreElder abuse has devastating consequences for older persons such as a poor quality of life, psychological distress, and loss of property and security. It is also associated with increased mortality and morbidity. Elder abuse is a problem that manifests itself in both rich and poor countries and at all levels of society. It is timely to discuss one of the basic problems that has hampered the study, detection and intervention of elder abuse as the variety of definitions that exist now produce a definitional chaos for researchers, practitioners, and policy makers. In this article we trace the elements of “how to define elder abuse” and situate them in their socio-historical context. We also analyze the purposes of these different definitions to assess their appropriateness in different settings concerned with elder abuse. Our analysis shows that elder abuse mirrors the societal arrangements which gave rise to them. It also highlights that it is a complex problem that is difficult to define. The central question is whether we need a common definition of elder abuse or different definitions that can be used in different settings. By evidence of our analysis we can see that there is a need for a sufficiently broad and flexible definition in order to cover different behaviors that can constitute abuse and the various settings in which it may occur. On the other hand, the definition needs to be specific and concrete to be useful in professional contexts. To take a further step forward for both research and practice of elder abuse, we propose to consistently adhere to the WHO definition that leads the enquirer towards a better understanding of the problem and helps to distinguish it from other phenomena; and to a simplified definition for professional practice that sets boundaries to the phenomena and is appropriate for effective prevention and intervention measures Show less
Engelaer, Frouke M.; Bodegom, David van; Westendorp, Rudi G.J. 2012
Various studies in mice have found support for the hypothesis that heterozygous carriers of cystic Wbrosis transmembrane conductance regulator (CFTR) mutations have an increased resistance to fatal... Show moreVarious studies in mice have found support for the hypothesis that heterozygous carriers of cystic Wbrosis transmembrane conductance regulator (CFTR) mutations have an increased resistance to fatal infection compared to both homozygous mutation carriers and non-carriers, while in humans such evidence is scarce. In this study, we assessed the CFTR heterozygotes survival advantage hypothesis in a contemporary rural population that lives under adverse environmental conditions in the Upper-East region of Ghana. We genotyped 30 SNPs throughout the CFTR gene in 4,230 participants and tested their inXuence on survival and on body composition in the population at large. With a sliding-window haplotype analysis, we identi- Wed a set of six common haplotypes that inXuenced survival probabilities (global p = 6.00 £ 10¡05). Individual haplotype analyses revealed two haplotypes of speciWc interest. One of these haplotypes was enriched (p = 0.003), whereas the other was depleted (p = 0.041) among people of old age (¸65 years) compared to young study participants (·5 years). In addition, children (n = 474) carrying the latter haplotype had lower body weight (ptrend = 0.020) and height (ptrend = 0.010) compared to non-carriers. For all these analyses, similar associations for heterozygous and homozygous CFTR haplotype carriers were observed, revealing an additive eVect of haplotype alleles. In conclusion, we identiWed common haplotypes in the CFTR gene that inXuence survival and body composition in the population at large with no evidence for heterozygote advantage. Show less
Bodegom, David van; Rozing, Maarten; May, Linda; Kuningas, Maris; Thomese, Fleur; Meij, Hans; Westendorp, Rudi 2010
In a recent issue of this journal, Herndon [1] discussed the grandmother hypothesis and its implications for studies on cognitive ageing. According to this hypothesis, the long post-reproductive... Show moreIn a recent issue of this journal, Herndon [1] discussed the grandmother hypothesis and its implications for studies on cognitive ageing. According to this hypothesis, the long post-reproductive life span in human females is an adaptive mechanism that evolved to maximize female fitness by investing resources in the care of their grandchildren rather than by continuing to reproduce themselves. From this, Herndon deduces that special cognitive robustness to be maintained until after the age of menopause must have coevolved because grandmothers can only exert the beneficial effect if their cognitive abilities remain intact. He therefore pleas to compare cognitive ageing in humans with other primates, especially chimpanzees, because they lack a long post-reproductive life span and would therefore not have evolved this cognitive robustness. Here, we question the important role of grandmothers in our evolutionary past, first because of the different family structures during this time and second because of the low number of females that actually lived to experience a post-reproductive lifespan. We also show that in a population that reflects our evolutionary past, grandmothers do not have an important role for child survival. Finally, we react on the implications for the study of cognitive ageing as put forward by Herndon. Show less
May, Linda; Bodegom, David van; Frolich, Marijke; Lieshout, Lisette van; Slagboom, P Eline; Westendorp, Rudi GJ and Kuningas, Maris 2010
Toll-like receptors (TLRs) are involved in the induction of an adequate immune response on infection. We hypothesized that genetic variation in TLR4 and TLR2 genes could influence this response and... Show moreToll-like receptors (TLRs) are involved in the induction of an adequate immune response on infection. We hypothesized that genetic variation in TLR4 and TLR2 genes could influence this response and lead to variability in cytokine production and survival. We tested this hypothesis in 4292 participants who were followed up for all-cause mortality for 6 years and live under adverse environmental conditions in the Upper-East region of Ghana, where malaria is endemic. In 605 participants, tumor necrosis factor-a and interleukin-10 (IL10) production, after stimulation with lipopolysaccharide and zymosan, was measured. In addition, 34 single-nucleotide polymorphisms (SNPs) in TLR4 and 12 SNPs in TLR2 were genotyped and tested for association with cytokine production, malaria infection and mortality. In this comprehensive gene-wide approach, we identified novel SNPs in the TLR4 gene that influence cytokine production. From the analyzed SNPs, rs7860896 associated the strongest with IL10 production (P¼0.0005). None of the SNPs in this study associated with malaria or overall mortality risks. In conclusion, we demonstrate that genetic variation within the TLR4 gene influences cytokine production capacity, but in an endemic area does not influence the susceptibility to malaria infection or mortality. Show less
May, Linda; Kuningas, Maris; Bodegom, David van; Meij, Hans J.; Frolich, Marijke; Slagboom, P. Eline; ... ; and Westendorp, Rudi G.J. 2009
Pentraxin 3 (PTX3) plays an important role in innate immune responses and in female fertility, as discovered with studies in mice. However, the role of PTX3 in human fertility is unknown. Here, we... Show morePentraxin 3 (PTX3) plays an important role in innate immune responses and in female fertility, as discovered with studies in mice. However, the role of PTX3 in human fertility is unknown. Here, we report on a population-based study from a rural area of Upper East Ghana (n ¼ 4346). We studied the association between the number of children given birth by women during their lifetime and ex vivo, lipopolysaccharide (LPS)-induced PTX3 production (n ¼ 362). In addition, we studied the association of genetic variation in the PTX3 gene with PTX3 production (n ¼ 617) and with female fertility (n ¼ 1999). We found that ex vivo LPS-induced PTX3 production was associated with fertility (P ¼ 0.040). Furthermore, we identified genetic variants in the PTX3 gene that influence PTX3 production, and also fertility. The strongest associations were observed for the rs6788044 single-nucleotide polymorphism (SNP). We found that carriers of this SNP had higher PTX3 production capacity (P ¼ 0.003) and higher fertility (P ¼ 0.043). The results reported here provide the first evidence, based on protein production and analysis of polymorphisms, that the long pentraxin PTX3 plays a role in female fertility in humans. Show less
May, Linda; Biggelaar, Anita HJ van den; Bodegom, David van; Meij, Hans J; Craen, Anton JM de; Amankwa, Joseph; ... ; Kuningas, Maris and Westendorp, Rudi GJ 2009
Background-: The innate immune system plays an important role in the recognition and induction of protective responses against infectious pathogens, whilst there is increasing evidence for a role... Show moreBackground-: The innate immune system plays an important role in the recognition and induction of protective responses against infectious pathogens, whilst there is increasing evidence for a role in mediating chronic inflammatory diseases at older age. Despite indications that environmental conditions can influence the senescence process of the adaptive immune system, it is not known whether the same holds true for the innate immune system. Therefore we studied whether agerelated innate immune responses are similar or differ between populations living under very diverse environmental conditions. Methods-: We compared cross-sectional age-related changes in ex vivo innate cytokine responses in a population living under affluent conditions in the Netherlands (age 20–68 years old, n = 304) and a population living under adverse environmental conditions in Ghana (age 23–95 years old, n = 562). Results-: We found a significant decrease in LPS-induced Interleukin (IL)-10 and Tumor Necrosis Factor (TNF) production with age in the Dutch population. In Ghana a similar age-related decline in IL-10 responses to LPS, as well as to zymosan, or LPS plus zymosan, was observed. TNF production, however, did not show an age-associated decline, but increased significantly with age in response to co-stimulation with LPS and zymosan. Conclusion-: We conclude that the decline in innate cytokine responses is an intrinsic ageing phenomenon, while pathogen exposure and/or selective survival drive pro-inflammatory responses under adverse living conditions. Show less
Bodegom, David van; May,Linda; Kuningas, Maris; Kaptijn, Ralf; Thomése, Fleur; Meij, Hans J.; ... ; Westendorp, Rudi G.J. 2009
Socio-economic status is an important determinant of health and survival in rural Africa and necessitates a practical and valid instrument to implement in health studies. Our objective was to... Show moreSocio-economic status is an important determinant of health and survival in rural Africa and necessitates a practical and valid instrument to implement in health studies. Our objective was to investigate the validity of the rapid appraisal method to assess socio-economic status and its ability to identify individuals at risk. Among 1573 households in rural northern Ghana, we calculated the Demographic Health Survey (DHS) wealth index and conducted two rapid appraisal methods: self-reported wealth and interviewer-reported wealth. In addition we followed the 25 184 participants from these households for survival with a mean follow-up of 3.9 years, during which 885 participants died. The DHS wealth index was moderately correlated to self-reported wealth (Spearman’s 0.59, P < 0.001) and interviewer-reported wealth (Spearman’s 0.75, P < 0.001). Mortality risks were significantly higher for people with lower than average self-reported wealth [hazard ratio (HR) 1.30 (95% CI 1.11—1.51)] and lower interviewerreported wealth [HR 1.40 (95% CI 1.21—1.62)]. Mortality risks were lower for people with higher self-reported wealth [HR 0.81 (95% CI 0.32—2.03)] and higher interviewer-reported wealth [HR 0.84 (95% CI 0.58—1.21)]. Similar discriminative mortality risks were assessed when using tertiles of the DHS wealth index (Ptrend < 0.001). Show less
