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The apolipoprotein-ε4 allele (APOE-ε4) is strongly associated with detrimental outcomes in affluent populations including atherosclerotic disease, Alzheimer's disease, and reduced lifespan. Despite these detrimental outcomes, population frequencies of APOE-ε4 are high. We hypothesize that the high frequency of APOE-ε4 was maintained because of beneficial effects during evolution when infectious pathogens were more prevalent and a major cause of mortality. We examined a rural Ghanaian population with a high pathogen exposure for selective advantages of APOE-ε4, to survival and or fertility. This rural Ghanaian population (n = 4311) has high levels of mortality from widespread infectious diseases which are the main cause of death. We examined whether APOE-ε4 was associated with survival (total follow-up time was 30,262 years) and fertility after stratifying by exposure to high or low pathogen levels. Households drawing water from open wells and rivers were classified as exposed to high pathogen levels while low pathogen exposure was classified as those drawing water from borehole wells. We found a non-significant, but positive survival benefit, i.e. the hazard ratio per APOE-ε4 allele was 0.80 (95% confidence interval: 0.69 to 1.05), adjusted for sex, tribe, and socioeconomic status. Among women aged 40 years and older (n = 842), APOE-ε4 was not associated with the lifetime number of children. However, APOE-ε4 was associated with higher fertility in women exposed to high pathogen levels. Compared with women not carrying an APOE-ε4 allele, those carrying one APOE-ε4 allele had on average one more child and those carrying two APOE-ε4 alleles had 3.5 more children (p = 0.018). Contrary to affluent modern-day populations, APOE-ε4 did not carry a survival disadvantage in this rural Ghanaian population. Moreover, APOE-ε4 promotes fertility in highly infectious environments. Our findings suggest that APOE-ε4 may be considered as evolutionarily adaptive. Its adverse associations in affluent modern populations with later onset diseases of aging further characterize APOE-ε4 as an example of antagonistic pleiotropy.

Background and aimSustained lifestyle changes are crucial for the remission of type 2 diabetes (T2D) but remain challenging. Citizen initiatives using peer coaching and self-management may offer a promising alternative to professional medical care. This study evaluated Your Lifestyle As Medicine (YLAM), a Dutch citizen initiative for people with T2D. We aimed to assess its impact on metabolic parameters and to examine participants’ engagement.MethodsThis observational study analysed self-reported data on weight, waist circumference, fasting glucose and glycated haemoglobin (HbA1c) from participants in YLAM’s online community. Participants could report their self-measured data on a weekly basis. Linear mixed-model analyses, stratified by sex, were used to assess changes in metabolic parameters over time. Additionally, we evaluated participants’ engagement through reporting duration and weekly reporting rates.ResultsWe assessed all 232 people with T2D who reported multiple measurements for at least 3 months. The median reporting duration was 11.2 months (IQR 4.6–26.5). Weekly reporting rates were 59% for weight, 55% for waist circumference and 52% for fasting glucose, and 12-weekly reporting rates were 49% for HbA1c. Overall, mean weight, waist circumference, fasting glucose and HbA1c improved in the first year in both women and men. More specifically, weight decreased by 7.2 kg in women (95% CI –7.6 to –6.8) and by 7.4 kg in men (95% CI –8.0 to –6.8). This represented a mean relative weight loss of 9.0% (SD 7.7) and 8.6% (SD 6.5), respectively. Waist circumference decreased by 8.9 cm in women (95% CI –9.4 to –8.5) and by 8.5 cm in men (95% CI –9.1 to –7.8). Fasting glucose decreased by 1.15 mmol/L in women (95% CI –1.32 to –0.98) and by 0.49 mmol/L in men (95% CI –0.75 to –0.23). HbA1c decreased by 14.5 mmol/mol in women (95% CI –17.4 to –11.6) and by 9.1 mmol/mol in men (95% CI –13.2 to –5.0). Of all participants, 44% reported data for longer than a year and demonstrated sustained improvements in weight and waist circumference in the long term.ConclusionThis study provides evidence for substantial and sustained improvements in self-reported metabolic parameters in people with T2D engaged in a citizen initiative without medical supervision. Initiatives like YLAM offer a promising, accessible and scalable strategy to address the growing burden of lifestyle-related diseases.

IntroductionPhysical activity (PA) decreases the risk of mental diseases. Although PA timing has been hypothesised to affect mental health outcomes, no large-scale epidemiological cohort studies have been performed. We investigated the association between PA timing and incident depression in the general population.MethodsA total of 89 934 European participants (62.4±7.9 years, age range: 43–79 years, 44.8% men) without a history of depression were analysed. Hourly PA levels were derived from accelerometry data and standardised for the total daily amount of PA. Participants were followed for a maximum of 8.5 years. Risks of incident depression dependent on individually standardised hourly PA level were assessed using Cox proportional-hazards models adjusted for potential confounders.ResultsDuring follow-up, 1748 participants developed depression. Using the hourly standardised PA levels, we observed higher risks for incident depression with higher night-time PA (eg, at 4:00 HR 1.35; 95% CI 1.28, 1.41), and lower depression risks with higher morning-time PA (eg, at 9:00 HR 0.85; 95% CI 0.81, 0.89). Also in the subgroup analysis, compared with participants who were most active during midday, participants with most PA in the early morning had a lower risk for incident depression (HR 0.80; 95% CI 0.68, 0.95). No differences were observed when analyses were stratified for sex, chronotype or for the overall objective PA level.ConclusionsMorning PA was associated with lower risk and night-time PA was associated with increased risk of depression. These findings may suggest that future intervention studies should include timing as an additional dimension of PA as a possible treatment and prevention strategy for depression.

The Dutch population is rapidly ageing, and a growing number of people are suffering from age-related health problems such as obesity, cardiovascular diseases and diabetes. These diseases can be prevented or delayed by adapting healthy behaviours. However, making long-lasting lifestyle changes has proven to be challenging and most individual-based lifestyle interventions have not been effective on the long-term. Prevention programs focused on lifestyle should involve the physical and social context of individuals, because the (social) environment plays a large role in both conscious and unconscious lifestyle choices. Collective prevention programmes are promising strategies to mobilize the potential of the (social) environment. However, little is known about how such collective prevention programs could work in practice. Together with community care organization Buurtzorg, we have started a 5 year evaluation project to study how collective prevention can be practised in communities. In this paper, we discuss the potential of collective prevention and explain the methods and goals of our study.

Background There are increased indications that physical activity timing, irrespective of intensity, impacts insomnia and circadian clock function. Here, we describe the rationale and design of a randomized cross-over study, called ON TIME, to examine the effects of (changing) physical activity timing on insomnia severity and on multiple exploratory outcomes that are linked to circadian clock function. Methods We will conduct a randomized cross-over trial in 40 healthy older adults (aged 65 to 75 years) with subclinical or clinical insomnia (Insomnia Severity Index (ISI) scores of ≥ 10) from the Dutch municipality of Leiden and surroundings. Participants will undergo 3 intervention periods (14 days each) consecutively: one sedentary period and two periods of increased physical activity (one period with morning activity and one period with evening activity). The intervention periods are separated by a wash-out period of 1 week. In both active intervention arms, participants will follow coached or uncoached outdoor physical exercise sessions comprising endurance, strength, and flexibility exercises for 14 days. The primary outcome is change in insomnia severity as measured by the ISI. Additional exploratory outcomes include multiple components of objective sleep quality measured with tri-axial accelerometry and subjective sleep quality assessed by questionnaires as well as dim light melatonin onset and 24-h rhythms in heart rate, heart rate variability, breathing rate, oxygen saturation, mood, and objective emotional arousal and stress. Additionally, we will collect diary data on eating patterns (timing and composition). Finally, fasting blood samples will be collected at baseline and after each intervention period for measurements of biomarkers of metabolic and physiological functioning and expression of genes involved in regulation of the biological clock. Discussion We anticipate that this study will make a significant contribution to the limited knowledge on the effect of physical activity timing. Optimizing physical activity timing has the potential to augment the health benefits of increased physical exercise in the aging population. Trial registration Trial was approved by the Medical Ethics Committee Leiden, The Hague, Delft, The Netherlands (June, 2023). The trial was registered in the CCMO-register https://www.toetsingonline.nl/to/ccmo_search.nsf/Searchform?OpenForm under study ID NL82335.058.22 and named (“Ouderen op tijd in beweging” or in English “Older adults exercising on time”). At time of manuscript submission, the trial was additionally registered at ClinicalTrials.gov under study ID: NL82335.058.22 and is awaiting approval.

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 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.

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. 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. 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. 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 community-dwelling elderly. Policy-makers, epidemiologists and health economists are urged to acknowledge and include the impact of the seasons in future policy and research.

To test the inflammatory origin of cardiovascular disease, as opposed to its origin in western lifestyle. Population-based assessment of the prevalences of cardiovascular risk factors and cardiovascular disease in an inflammation-prone African population, including electrocardiography and ankle-arm index measurement. Comparison with known prevalences in American and European societies. Traditional population in rural Ghana, characterised by adverse environmental conditions and a high infectious load. Population-based sample of 924 individuals aged 50 years and older. Median values for cardiovascular risk factors, including waist circumference, BMI, blood pressure, and markers of glucose and lipid metabolism and inflammation. Prevalence of myocardial infarction detected by electrocardiography and prevalence of peripheral arterial disease detected by ankle-arm index. When compared to western societies, we found the Ghanaians to have more proinflammatory profiles and less cardiovascular risk factors, including obesity, dysglycaemia, dyslipidaemia, and hypertension. Prevalences of cardiovascular disease were also lower. Definite myocardial infarction was present in 1.2% (95%CI: 0.6 to 2.4%). Peripheral arterial disease was present in 2.8% (95%CI: 1.9 to 4.1%). Taken together, our data indicate that for the pathogenesis of cardiovascular disease inflammatory processes alone do not suffice and additional factors, probably lifestyle-related, are mandatory.

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. 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 affected most. 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. Mean monthly health care expenditure in married subjects was € 502 in the 42 months before the death of the spouse, and expenditure levels rose by € 239 (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 (€ 319; 59%) and the oldest old (€ 553; 82%). Expenditure levels showed the highest increase for hospital and home care services (together € 166). 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.

Many age-related diseases can be prevented or delayed by daily physical activity. Unfortunately, many older adults do not perform physical activity at the recommended level. Professional interventions do not reach large numbers of older adults for a long period of time. We studied a peer-coach intervention, in which older adults coach each other, that increased daily physical activity of community dwelling older adults for over 6 years. We studied the format and effects of this peer coach intervention for possible future implementation elsewhere. Through interviews and participatory observation we studied the format of the intervention. We also used a questionnaire (n = 55) and collected 6-min walk test data (n = 261) from 2014 to 2016 to determine the motivations of participants and effects of the intervention on health, well-being and physical capacity. Vitality Club is a self-sustainable group of older adults that gather every weekday to exercise coached by an older adult. Members attend on average 2.5 days per week and retention rate is 77.5% after 6 years. The members perceived improvements in several health measures. In line with this, the 6-min walk test results of members of this Vitality Club improved with 21.7 meters per year, compared with the decline of 2–7 meters per year in the general population. This Vitality Club is successful in durably engaging its members in physical activity. The members perceive improvements in health that are in line with improvements in a physical function test. Because of the self-sustainable character of the intervention, peer coaching has the potential to be scaled up at low cost and increase physical activity in the increasing number of older adults.