European Journal Of Epidemiology[JOURNAL]
Sun
200 papers
Are all ultra-processed foods created equal? Relevance of food processing and nutritional quality.
Mendoza K, Hu FB
Eur J Epidemiol · 2025 Nov · PMID 41182537 · Publisher ↗
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Cohort profile and representativeness of participants in the Danish monozygotic twin study on migraine.
Olofsson IA, Olesen J, Christensen K … +2 more , Hoffmann ER, Hansen TF
Eur J Epidemiol · 2025 Nov · PMID 41182536 · Full text
The Danish Monozygotic Twin Study on Migraine is a population-based twin study established in 2023-2024. The cohort was created to lay the foundation for innovative studies of the role of environmental, genetic, and epig...
The Danish Monozygotic Twin Study on Migraine is a population-based twin study established in 2023-2024. The cohort was created to lay the foundation for innovative studies of the role of environmental, genetic, and epigenetic factors and their complex interactions in the pathogenesis of migraine. The aim of this paper is to describe data collection, content, characteristics of participants and to assess the representativeness of the cohort by comparing participants to non-responders. Danish monozygotic twins born between 1967 and 2000 were invited to participate. Self-reported questionnaires were sent out to 9,036 possible participants. The questionnaires assessed migraine and migraine subtypes, life satisfaction, resilience, stress, childhood trauma and the relationship of the participant to their family. Through linkage to the nationwide Danish registries the cohort contains individual level information on education, income, patient data from hospitals, prescription medication and childbirth. The Danish registries also enable longitudinal data collection on health outcomes. Individuals who responded to the migraine questionnaire were defined as participants. The cohort consists of 3,893 individuals, including 1,822 complete twin pairs, 1,173 individuals with migraine and 280 migraine discordant twin pairs. 123 participants were included in a substudy with a migraine diagnostic interview and collection of blood samples for both genetic and epigenetic studies. Comparison between participants and non-responders showed a higher participation rate among women. For both genders participants were older, had a higher level of education and a higher level of income compared to non-responders. Sociodemographic differences in participation should be considered to avoid biased estimates in future studies based on the cohort.
Moderate alcohol drinking and incident dementia: a risk assessment.
Kawada T
Eur J Epidemiol · 2026 Jan · PMID 41171557 · Publisher ↗
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The early-onset cancer epidemics: evidence synthesis using the prospective cohort incident-tumor biobank method.
Ogino S, Ugai S, Hamada T … +1 more , Ugai T
Eur J Epidemiol · 2025 Dec · PMID 41144114 · Publisher ↗
Tumors likely develop over years/decades, implying that assessing long-term exposure to risk factors is crucial in cancer epidemiology. An increasing trend of long-term risk factor exposures starting from early life sinc...
Tumors likely develop over years/decades, implying that assessing long-term exposure to risk factors is crucial in cancer epidemiology. An increasing trend of long-term risk factor exposures starting from early life since the mid-twentieth century appears to have contributed to the epidemics of early-onset cancer (EOC) worldwide. A rising incidence of EOC has been reported in various body sites such as the bone marrow, bile duct, breast, colorectum, esophagus, gallbladder, head and neck, kidney, liver, pancreas, stomach, and uterine corpus. To address an intractable gap between long-term exposure assessments and tumoral molecular/microenvironmental profiling in EOC research, here we describe a framework using the prospective cohort incident-tumor biobank method (PCIBM), which was recently conceptualized. The PCIBM enables prospective molecular pathological epidemiology research that can link long-term exposures with tumor pathogenic signatures. We illustrate this framework using the study of early-onset colorectal cancer (EOCRC). First, one recognizes overlaps of the characteristics of EOCRC and later-onset counterparts. Second, EOCRC tumoral, multi-omic, or microenvironmental features are discovered and replicated. Third, using the PCIBM, long-term exposure variables are examined in relation to the incidence of all-age colorectal cancer subtypes possessing EOCRC tumoral features. Fourth, identified putative risk factors are tested for EOCRC incidence. This framework, which has provided etiological insights and advanced our understanding of EOCRC pathogenesis, is widely applicable to EOC in various organs. In addition, this research modality with artificial intelligence-driven computational tools should be used in lifecourse and other prospective cohort studies to improve our knowledge of EOC pathogenesis.
The association between a pro-inflammatory diet and brain age in middle-aged and older adults.
Dunk MM, Huang H, Wang J … +6 more , Dove A, Sakakibara S, Guo J, Carballo-Casla A, Bennett DA, Xu W
Eur J Epidemiol · 2026 Jan · PMID 41144113 · Full text
Pro-inflammatory diets are associated with cognitive decline and dementia, but their impact on brain aging is unclear. We investigated the association between a pro-inflammatory diet and brain age, taking into account ag...
Pro-inflammatory diets are associated with cognitive decline and dementia, but their impact on brain aging is unclear. We investigated the association between a pro-inflammatory diet and brain age, taking into account age, genetic risk for dementia, and systemic inflammation. UK Biobank participants (N = 21,473) aged 40-70 years and free of neurological disorders were included. The Dietary Inflammatory Index (DII) was calculated from participants' average intake of 31 nutrients, assessed up to five times via 24-h recalls. Participants were categorized into four DII groups (group 1, anti-inflammatory, DII < -2; group 2, DII -2 to < 0; group 3, DII 0 to < 2; group 4, DII ≥ 2), with group 4 reflecting the most pro-inflammatory diet. Brain age was estimated using a machine learning model based on 1079 structural and functional MRI measures, obtained approximately 9 years after baseline. We calculated brain age gap (BAG; brain age minus chronological age), where BAG > 0 reflects a biologically older brain than chronological age. An Alzheimer's disease polygenic risk score (PRS), APOE4 status, and a composite score of systemic inflammation (INFLA-score) were determined from baseline blood samples. More pro-inflammatory diets were associated with increasingly greater BAG, with advanced brain age by [Formula: see text]=0.50 [95% CI 0.20, 0.80] years among those in group 4. There were no interactions between DII and age, PRS, or APOE4 in relation to BAG, but associations were stronger among adults ≥ 60 years. INFLA-score mediated 8% of the DII-BAG association. These findings suggest that a pro-inflammatory diet may accelerate brain aging, especially in older adults.
Who got tested and who got sick? Sociodemographic inequalities in COVID-19 testing and hospitalization among 1.48 million individuals in Sweden.
Östergren OM, Counil E, Karimi A … +3 more , Fall T, Björk J, Gauffin K
Eur J Epidemiol · 2025 Dec · PMID 41144112 · Full text
In the early stages of the COVID-19 pandemic, PCR testing served different purposes for individuals and for policy makers. Policy makers relied on testing for representative case numbers to track and mitigate the spread...
In the early stages of the COVID-19 pandemic, PCR testing served different purposes for individuals and for policy makers. Policy makers relied on testing for representative case numbers to track and mitigate the spread of the disease whereas individuals needed tests to protect themselves and others, or to travel or go work. Systematic differences in testing across population groups can bias case numbers, making it more difficult for policy makers to implement effective non-pharmaceutical interventions. We link records of 494 699 PCR-tests taken between 2020-07-01 and 2020-12-31 to individual records in several administrative registers for 1 480 126 working age individuals in the counties of Stockholm and Scania in Sweden. We estimate the likelihood of getting tested, test positivity rate and hospitalization risk by sex, household size, migration background, education, income and medical risk factors in the individual or in the household using regression models with age, occupation and neighbourhood as fixed effects. We find that testing behaviour vary independently by several demographic, socioeconomic and medical factors. Several groups that were at an elevated risk of being hospitalized for COVID-19, including men, individuals born outside Europe and those with low education, had low testing rates and high positivity rates. Numbers of confirmed SARS-CoV-2 infections reflect both infection rates and the testing behaviour of the population. To improve the utility of testing in future pandemics, policy makers may collect data on negative tests and dedicate part of the testing capacity for representative screening.
The effect of long-term adherence to physical activity recommendations in midlife on plasma proteins associated with frailty in the Atherosclerosis Risk in Communities (ARIC) study.
Liu F, Schrack JA, Walker KA … +6 more , Walston J, Mathias RA, Griswold ME, Palta P, Windham BG, Jackson JW
Eur J Epidemiol · 2026 Jan · PMID 41144111 · Full text
Clinical trials have shown favorable effects of exercise on frailty, supporting physical activity (PA) as a treatment and prevention strategy. Proteomics studies suggest that PA alters levels of many proteins, some of wh...
Clinical trials have shown favorable effects of exercise on frailty, supporting physical activity (PA) as a treatment and prevention strategy. Proteomics studies suggest that PA alters levels of many proteins, some of which may function as molecules in the biological processes underlying frailty. However, these studies have focused on structured exercise programs or cross-sectional PA-protein associations. Therefore, the effects of long-term PA on frailty-associated proteins remain unknown. Among 14,898 middle-aged adults, we emulated a target trial that assigned individuals to either (i) achieve and maintain the recommended PA level (≥ 150 min/week of moderate-to-vigorous physical activity [MVPA]) through 6 (± 0.3) years of follow-up or (ii) follow a "natural course" strategy, where all individuals engage in various amounts of habitual MVPA. We estimated the effects of long-term adherence to recommended MVPA versus the natural course strategy on 45 previously identified frailty-associated proteins at the end of the follow-up using inverse probability of weighting (IPW) and iterative conditional expectations (ICE). We found that long-term adherence to recommended MVPA improved the population levels of many frailty-associated proteins (ranged from 0.04 to 0.11 standard deviation); the greatest benefits were seen in proteins involved in the nervous system (e.g., voltage-dependent calcium channel subunit alpha-2/delta-3 [CACNA2D3], contactin-1 [CNTN1], neural cell adhesion molecule 1 [NCAM1], and transmembrane protein 132D [TMEM132D]) and inflammation (e.g., high-temperature requirement serine protease A1 [HTRA1] and C-reactive protein [CRP]). Our findings suggest improved nervous system and reduced inflammation as the biological basis of long-term engagement in adequate PA as an intervention strategy for frailty.
Coffee and tea intake, circulating inflammatory biomarkers, and long-term risk of dementia: findings from two longitudinal studies.
Yan M, Shen J, Zhao M … +10 more , Fei L, Huang Y, Wu M, Shen T, Hailili G, Liu D, Zong G, Zheng Y, Hang D, Yuan C
Eur J Epidemiol · 2026 Jan · PMID 41144110 · Publisher ↗
The associations of coffee and tea intake with long-term risk of dementia have not been thoroughly established. Additionally, the potential mediating roles of circulating inflammatory biomarkers in these associations rem...
The associations of coffee and tea intake with long-term risk of dementia have not been thoroughly established. Additionally, the potential mediating roles of circulating inflammatory biomarkers in these associations remain less explored. We included 6,001 participants from the Health and Retirement Study (HRS, 2013-2020) and 2,650 participants from the Framingham Heart Study Offspring cohort (FOS, 1998-2018), all free of dementia at baseline. Coffee and tea intake was assessed using a semi-quantitative food frequency questionnaire in both cohorts. Dementia diagnosis was ascertained using a validated algorithm and clinical review panel. Cox proportional hazard models were utilized to evaluate the associations of coffee and tea intake with dementia. Mediation analysis was conducted to examine whether circulating inflammatory biomarkers mediated these associations. During a median follow-up of 7.0 years in HRS and 11.1 years in FOS, 231 individuals in HRS and 204 in FOS developed all-cause dementia. Compared with intake of less than 1 cup of coffee per day, consuming ≥ 2 cups daily had a 28-37% lower risk of dementia (Hazards ratio [HR] = 0.72, 95% confidence interval [CI]: 0.52, 0.99, P-trend = 0.045 in HRS; HR = 0.63, 95% CI: 0.45, 0.90, P-trend = 0.015 in FOS). Compared to non-consumers, moderate tea consumption was associated with a lower dementia risk in HRS (HR = 0.65, 95% CI: 0.48, 0.89 for > 0 to < 1 cup/day; HR = 0.53, 95% CI: 0.30, 0.94 for ≥ 1 to < 2 cups/day), but no significant association was observed in FOS. In the mediation analysis, the association between coffee intake and dementia was partially mediated by interleukin-10 (IL-10, 29.30%), Cystatin C (24.45%), C-reactive protein (CRP, 16.54%), interleukin-1 receptor antagonist (IL-1RA, 11.06%), and soluble tumor necrosis factor receptor-1 (sTNFR-1, 10.78%). In conclusion, higher coffee consumption (≥ 2 cups per day) is associated with a lower risk of dementia, partially mediated by a set of inflammatory biomarkers. Moderate intake of tea (0-2 cups per day) may relate to a lower risk of dementia. Further large-scale observational and interventional studies are warranted to confirm these findings.
The validity of the information on date of diagnosis of intracranial tumors in the Swedish cancer register.
Kaijser M, Feychting M, Skare S … +1 more , Fang F
Eur J Epidemiol · 2026 Jan · PMID 41137898 · Full text
PURPOSE: To assess the validity of information on the date of diagnosis of intracranial tumors in the Swedish National Cancer Register. MATERIALS AND METHODS: The study was conducted in Region Stockholm, covering approxi...
PURPOSE: To assess the validity of information on the date of diagnosis of intracranial tumors in the Swedish National Cancer Register. MATERIALS AND METHODS: The study was conducted in Region Stockholm, covering approximately 2.4 million inhabitants. Data from the Image and Function Service (BFT) archive, which contains a population-based database of all diagnostic radiology in the Stockholm Region, was used. The study included all primary cases of intracranial tumors (ICD10 codes C70 and C71) reported from Stockholm to the National Cancer Register from 2010 to 2020. Radiology reports from CT and MRI exams performed from 2000 to 2020 were reviewed. Reports from exams conducted more than one month before the Swedish Cancer Register diagnosis were manually examined to validate the date of diagnosis. RESULTS: For 98.8% of the brain tumor patients and 96.2% of the meningioma patients, the date of first radiological diagnosis was one month or less prior to date of diagnosis in the Swedish Cancer Register. Of the patients with radiological diagnoses more than one month prior to cancer register diagnosis, 30 patients (1.0%) had tumors reported to the register one month to one year after radiological diagnosis, and 36 patients (1.2%) had tumors reported more than one year later. CONCLUSION: The study found that for patients from the Stockholm Region with intracranial tumors reported to the Swedish Cancer Register during the period 2010 through 2020, date of diagnosis is highly accurate.
Estimating overall survival by combining administrative and hospital death data: a methodological challenge.
Cren PY, Leguillette C, Craynest F … +7 more , Hammoudi A, Barthoulot M, Carton M, Filleron T, Chabaud S, Drouet Y, Le Deley MC
Eur J Epidemiol · 2026 Jan · PMID 41118097 · Publisher ↗
Since 2019, death data published by the Institute of Statistics and Economic Studies (INSEE) are available, raising questions regarding methodology and potential biases in overall survival analyses. We conducted a simula...
Since 2019, death data published by the Institute of Statistics and Economic Studies (INSEE) are available, raising questions regarding methodology and potential biases in overall survival analyses. We conducted a simulation study to quantify biases and formulate recommendations for using these data for research. We compared several approaches for estimating overall survival by (i) including only hospital data (EMR), (ii) adding deaths known to the INSEE (EMR_INSEE), or (iii) considering patients without reported death as "alive" (EMR_INSEE_IMP). We conducted simulation studies by varying the mortality risk of the disease studied, rate of loss to follow-up, and death capture rate from INSEE. With the EMR_INSEE approach, the risk of bias appeared to be significant in all clinical scenarios, with a large underestimation of overall survival. On comparing two survival curves, the hazard ratio estimate was highly biased, and type-I and II errors were inflated. With the EMR_INSEE_IMP approach, the risk of bias seemed low and acceptable for clinical situations involving low mortality, especially if loss to follow-up was low. However, some clinical situations seemed to require greater vigilance because of risk of bias when mortality was intermediate or high, especially when the risk of loss to follow-up was high. To our knowledge, this is the first study to assess the impact of using INSEE data in addition to hospital data on vital status. Various simulated scenarios enabled us to quantify the biases involved and thus make recommendations on the various possible strategies for using these data.
An in-depth study of the correlation between Hashimoto's thyroiditis and Sjogren's syndrome: multiple evidences from large cohorts, Mendelian randomization, and transcriptomic analysis.
Du Y, Kang ZJ, Tong Q … +5 more , Jiang HL, Cui R, Wang SI, Wei JC, Dai SM
Eur J Epidemiol · 2026 Jan · PMID 41085844 · Publisher ↗
The co-occurrence of Hashimoto's thyroiditis (HT) and Sjogren's syndrome (SS), two seemingly unrelated diseases that both affect huge amounts of people worldwide, has been indicated previously in several case reports. Ho...
The co-occurrence of Hashimoto's thyroiditis (HT) and Sjogren's syndrome (SS), two seemingly unrelated diseases that both affect huge amounts of people worldwide, has been indicated previously in several case reports. However, there is a lack of higher-level evidences proving their comorbidity, and the underlying mechanisms remain unelucidated. This in-depth study aims to provide evidences for the comorbidity between HT and SS and explore the genetic and immunological mechanisms that may underlie their occurrence. Leveraging large retrospective cohorts from the collaborative electronic health record database, matched by propensity scores, we evaluated the risk of developing SS in 190,653 patients with HT and the risk of developing HT in 73,306 patients with SS. A Mendelian randomization (MR) approach was applied to investigate the causal relationship between the two conditions. Transcriptomic analysis of GEO datasets further explored common immunological markers. Our large-scale propensity score-matched analysis revealed a significantly higher risk of SS in HT patients compared to controls, with a hazard ratio (HR) of 3.227 and a confidence interval (CI) of 2.987-3.486, over a 20-year follow-up period. Similarly, a reciprocal risk was observed, with SS patients at a higher risk of developing HT (HR, 2.780; CI, 2.568-3.009) compared to controls. In Mendelian randomization study, random-effects IVW method showed a potential causal effect of HT on SS (IVW OR = 1.871, 95% CI = 1.265-2.768; P = 0.002). Furthermore, transcriptomic analysis showed there were 127 common up-regulated differential expressed genes (DEGs) between HT and SS, accounting for 29.4% of upregulated DEGs in HT and 14.5% of upregulated DEGs. Common hub genes in HT and SS were also determined, including CD4, IFNG, CCR7, and ITGAM, suggesting a shared immunopathogenesis and highlighting potential therapeutic targets. Our findings revealed a strong correlation between HT and SS, supported by evidences from clinical cohorts, the genetical causal effect, and shared immunopathogenesis, offering new insights into the cooccurrence of the two diseases.
Association between chronic diseases in childhood and subsequent educational achievement: a Danish register-based cohort study.
Buchardt AS, Jensen A, Kildegaard H … +1 more , Stensballe LG
Eur J Epidemiol · 2026 Jan · PMID 41085843 · Full text
Severe chronic disease (SCD) in childhood may hinder not only physical health but also academic performance. In this population-based cohort study, we investigated educational outcomes among 20,979 Danish children with S...
Severe chronic disease (SCD) in childhood may hinder not only physical health but also academic performance. In this population-based cohort study, we investigated educational outcomes among 20,979 Danish children with SCD (54.7% male) and 423,814 without SCD (51.1% male). We assessed completion of lower secondary school and grade point averages (GPAs). Completion and GPAs with 95% confidence intervals (95% CI) were estimated using logistic and linear regression models adjusted for sex, country of origin, and maternal education. Children with SCD had lower probability of completing 9th grade (male: 0.53 [95% CI 0.52-0.54], female: 0.63 [0.62-0.64]) than their peers without SCD (male: 0.70 [0.70-0.70], female: 0.82 [0.81-0.82]). Similarly, GPA was lower for children with SCD (male: 6.61 [6.55-6.66], female: 7.51 [7.45-7.56]) compared to those without (male: 6.86 [6.85-6.87], female: 7.90 [7.89-7.91]). The sex disparity persisted across all groups. Children of mothers with lower education experienced larger performance gaps. Neurological and perinatal conditions showed the poorest outcomes. Our findings demonstrate persistent educational inequalities among children with SCD, even in settings with universal healthcare and education, underscoring the need for targeted, cross-sectoral support.
Associations of 2923 Olink proteins with demographic, lifestyle, environmental and health characteristics in middle-aged Chinese adults.
Iona A, Wang B, Clarke J … +28 more , Chan K, Kakkoura MG, Clarke C, Wright N, Yao P, Mazidi M, Im PK, Rahmati M, Kartsonaki C, Morris S, Fry H, Millwood IY, Walters RG, Chen Y, Du H, Yang L, Avery D, Schmidt-Valle D, Li F, Yu C, Sun D, Lv J, Hill M, Li L, Clarke R, Bennett DA, Chen Z, China Kadoorie Biobank Collaborative Group
Eur J Epidemiol · 2025 Oct · PMID 41071435 · Full text
UNLABELLED: Previous studies have identified a large number of genetic variants affecting plasma levels of proteins, but little is known about the non-genetic factors influencing plasma levels of proteins in diverse popu...
UNLABELLED: Previous studies have identified a large number of genetic variants affecting plasma levels of proteins, but little is known about the non-genetic factors influencing plasma levels of proteins in diverse populations. We measured plasma levels of 2923 proteins, using Olink Explore platform, in 2006 participants (mean age = 50.8 years; 62% female; mean body mass index = 23.9 kg/m) in the China Kadoorie Biobank, without prior cardiovascular diseases. Linear regression analyses were used to assess the associations of individual proteins with 37 major exposures across multiple domains (e.g., socio-demographic, lifestyle, environmental, sample processing, reproductive factors, clinical measurements, and health-related indices), adjusted for potential confounders and multiple testing. These were further replicated and compared with findings in UK Biobank. Overall 31 exposures were associated with at least one protein, with age ( = 1154), sex ( = 827), body mass index ( = 869) showing the highest number of associations, followed by frailty index ( = 597), systolic blood pressure ( = 479), random plasma glucose ( = 387), ambient temperature ( = 292), and hepatitis B surface antigen positivity ( = 282), but with diet and physical activity showing little associations. Likewise, of the 2,923 proteins examined, 65% were associated with at least one exposure, with 25 proteins associated with ≥ 10 exposures, including five (CDH2, ADGRE2, ADGRD1, ACY1, MEGF9) after mutual adjustments. The patterns of associations were similar after further mutual adjustments for exposures examined but differed by sex, chiefly due to differences in lifestyle and reproductive factors. Most of the observed associations were replicated in the Europeans. For the purpose of Open Access, the author has applied a CC-BY public copyright license to any Author Accepted Manuscript version arising from this submission. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10654-025-01311-z.
The autism 'epidemic': misinterpretation, misinformation and conspiracy.
Fombonne E
Eur J Epidemiol · 2025 Sep · PMID 41071434 · Publisher ↗
The Secretary of the US Department of Health & Human Services (HHSS) recently claimed that US estimates of the prevalence of autism confirmed the existence of an autism epidemic. Furthermore, HHSS asserted that the autis...
The Secretary of the US Department of Health & Human Services (HHSS) recently claimed that US estimates of the prevalence of autism confirmed the existence of an autism epidemic. Furthermore, HHSS asserted that the autism epidemic was driven by an environmental toxin which he promised to find in the following months. These claims are contradicted by studies showing that progress in the understanding, detection, diagnosis and management of autism have fueled the increasing prevalence. HHSS statements are also in sharp contrast with the opinion of scientists who have monitored the upward trend in autism prevalence in the US and worldwide. In this Commentary, we address sequentially each misconception and misinterpretation proffered by HHSS. We show that changes in the definition of autism, in diagnostic criteria and practices, in case ascertainment in surveys, the inclusion of less severe forms of autism and other contextual factors such as improved awareness, de-stigmatization, advocacy, improved access to service and better insurance coverage have all converged in increasing the prevalence of autism and that presenting the rise on autism prevalence as an epidemic is misleading. Furthermore, given the strong heritability of autism, its genetic and phenotypic heterogeneity and the paucity of leads on environmental risk, the promise to find an environmental toxin causally related to autism in upcoming months appears at best preposterous. We warn about the return of false theories and already debunked hypotheses on the etiology of autism when empirical data are ignored, scientific methodology is dismissed and experts' opinions disdained.
The role of lipids in the effect of APOE2 on cognitive function: a causal mediation analysis.
Xiang Q, Lok JJ, Roth N … +7 more , Andersen SL, Perls TT, Song Z, Yashin AI, Mengel-From J, Patti GJ, Sebastiani P
Eur J Epidemiol · 2025 Dec · PMID 41042284 · Full text
Extensive research has examined the direct effect of APOE alleles on cognitive decline. However, there is limited investigation into the effect of APOE that is explained or mediated through molecular pathways, such as li...
Extensive research has examined the direct effect of APOE alleles on cognitive decline. However, there is limited investigation into the effect of APOE that is explained or mediated through molecular pathways, such as lipids. In this study, we performed a causal mediation analysis to estimate both the direct effect of APOE2 and its indirect effect through 24 lipid species on cognitive function, measured from the digital Clock Drawing Test (CDT) in 1228 Long Life Family Study (LLFS) participants. Results showed that APOE2 carriers completed the CDT significantly faster compared to common APOE3 carriers. Primary analysis identified two lipids (CE 18:3 and TG 56:5) protectively mediated the effect of APOE2 on cognitive function, resulting in shorter CDT think-time, ink-time, and total-time; conversely, TG 56:4 deleteriously mediated the effect of APOE2, resulting in increased ink-time. Secondary analysis yielded consistent results and identified four additional significant lipid pathways (DG 38:5, TG 51:3, TG 56:1, TG 56:2) that mediated the effect of APOE2. The combined indirect effect in the primary analysis contributed 15%-30% mediated proportion on CDT times, though such mediated proportion did not reach statistical significance. Overall, our analysis identified seven lipid species that significantly mediate the effect of APOE2 on cognitive performance. These lipids represent distinct lipid pathways, including both protective and deleterious mediation effects. Our findings offer insights for new therapeutics targeting those lipids to enhance the protective effects of APOE2 on cognition.
Adverse health outcomes associated with drinking highly saline water: a systematic review.
Costopoulos E, Imamura A, Khan N … +6 more , Butler A, Millett C, Hoque MA, Vineis P, Belesova K, Khan A
Eur J Epidemiol · 2025 Nov · PMID 41021114 · Full text
In climate change-affected coastal areas, sea level rise, storm surges, droughts and altered rainfalls are significantly increasing salinity levels in drinking water sources. This is a major public health problem that af...
In climate change-affected coastal areas, sea level rise, storm surges, droughts and altered rainfalls are significantly increasing salinity levels in drinking water sources. This is a major public health problem that affects many millions of people. We systematically reviewed and assessed the strength and quality of the evidence on the relationship between drinking water with high sodium levels (> 200 mgNa/l) and adverse cardiovascular, renal, and pregnancy-related health outcomes, following the PRISMA guidelines, the ROBINS-E Cochrane tool and the Navigation Guide. From five bibliographic databases, we identified 22 relevant studies, some of which assessed more than one health domain. The evidence was of moderate quality and strength. 14 analyses from eight studies at low risk of bias and four studies at moderate risk of bias, linked drinking high-salinity water to adverse health outcomes including hypertension and cardiovascular disease, impaired renal function, gestational hypertension and preeclampsia, and higher infant mortality. Eight studies were inconclusive. Three analyses, of which two at low risk of bias, associated drinking high-salinity water to improved health outcomes. Overall, our findings suggest that salinisation of drinking water sources is likely to increase adverse cardiovascular, renal, and pregnancy-related health outcomes. This conclusion highlights the importance of effective and timely adaptation at scale, and calls for a revision of the WHO guidelines for the intake of salt from water. The latest WHO guidelines (2022) do not set any health-based standard for sodium levels in drinking water, a problem that affects millions of people and will worsen with climate change.
Associations of alcohol drinking with incident dementia: a prospective study from the UK Biobank.
Chen Y, Yin X, Wang X … +5 more , Zheng X, Yang X, Zhou J, Shi M, Zhang Y
Eur J Epidemiol · 2025 Nov · PMID 41014391 · Publisher ↗
Relationship between alcohol drinking and incident dementia remained uncertain. This study used UK Biobank cohort data to investigate the association between alcohol drinking and dementia risk, and potential effect modif...
Relationship between alcohol drinking and incident dementia remained uncertain. This study used UK Biobank cohort data to investigate the association between alcohol drinking and dementia risk, and potential effect modifications by cardiovascular disease (CVD) risk, APOE4 gene, and sex. We excluded infrequent drinkers and participants with baseline dementia or dementia within two years of follow-up. Drinking status was defined as non-drinking, low-moderate and heavy drinking (by weekly alcohol units). Drinking behaviors included drinking with meals and drinking type. Primary outcome was all-cause dementia. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by multivariable Cox regression models. Subgroup analyses stratified by CVD risk, APOE4 gene, and sex were conducted. Among 296,715 participants (mean age 56.54 years), 4,242 developed dementia over a median follow-up of 13.7 years. Compared to non-drinking, low-moderate drinking reduced dementia risk (HR, 0.65; 95% CI, 0.59-0.73), while heavy drinking showed no significant association (HR, 0.88; 95% CI, 0.75-1.02). All drinking behaviors lowered dementia risk. Low-moderate drinking reduced dementia risk across subgroups: high/low CVD risk (HR 0.66, 95% CI 0.59-0.74/0.43, 0.30-0.61), APOE4 carriers/non-carriers (HR 0.71, 0.61-0.83/0.61, 0.52-0.71), females/males (HR 0.67, 0.58-0.77/0.63, 0.53-0.76). Compared with non-drinking, low-moderate drinking is associated with lower incident dementia risk, regardless of CVD risk, APOE4 gene, and sex. The protective effect of alcohol drinking was consistent among various drinking behaviors. Thus, this study confirmed the protective effect of low-moderate drinking in population, and provided insights for improving alcohol-related public health guidelines for dementia prevention.
Survival trends and cure rates of hematological neoplasms in the Spanish pediatric population.
Trallero J, Romaguera A, Ameijide A … +20 more , Cañete A, Pardo E, Alfonso P, Jeghalef-El-Karoui N, De-La-Cruz M, Onaindia-Agundez A, Sanvisens A, Redondo-Sánchez D, Perucha J, Ruiz-Armengol P, Chirlaque MD, Guevara M, Gutiérrez P, Pla C, Merino-Perera S, Garrido-Martín M, Vizcaino-Batlles A, Lopez-de-Munain A, Marcos-Gragera R, REDECAN
Eur J Epidemiol · 2026 Jan · PMID 40991150 · Publisher ↗
Hematological neoplasms (HN) were the first cause of death in children aged 5-9 years in Spain. The aim of this registry-based study is to provide a detailed overview of the survival of HN in the Spanish pediatric popula...
Hematological neoplasms (HN) were the first cause of death in children aged 5-9 years in Spain. The aim of this registry-based study is to provide a detailed overview of the survival of HN in the Spanish pediatric population. All pediatric HN cases included were classified according to the International Classification for Childhood Cancer. Flexible parametric models were used to estimate survival probabilities and long-term survival projections. Survival trends were evaluated with the annual average change in survival (AAC_S). Latent cure models were used to estimate cure fractions (CF). A total of 4706 cases of HN were diagnosed in Spain during 2000-2016, for which 2850 (60.6%) were boys. Leukemias and lymphoid leukemias (LL) were the most common type and subtype of HN in children. An overall 5- year survival of 84.3% [95% confidence intervals (CI): 83.3, 85.3] was observed for HNs. Children aged < 1 year with acute myeloid leukemia (AML) or myelodysplastic syndrome had the worst prognosis. An improvement over time was observed for all HN with an AAC_S of 0.71% [95% CI 0.50, 0.91], of which AML and Burkitt lymphomas displayed the greatest improvements. HNs revealed CF of 83.8% [95% CI 82.4, 85.3], with the highest CF being nearly 100% in Hodgkin lymphomas. Larger population coverage with updated data have aligned the Spanish results to those observed in other European countries. Continuous refinements in treatments, patient care and better diagnostic methods have revealed the highest survival improvements for HN subtypes with bad prognosis in children.
Null within-twin estimates on education and dementia: cautions for within-family contrasts.
Ko S
Eur J Epidemiol · 2025 Dec · PMID 40991149 · Publisher ↗
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Sex, male origin microchimerism, and mortality in a Danish cohort.
Petersen GL, Nguyen TL, Lindahl-Jacobsen R … +2 more , Tjønneland A, Kamper-Jørgensen M
Eur J Epidemiol · 2025 Nov · PMID 40991148 · Full text
We previously demonstrated that women with detectable male cells in peripheral blood – male origin microchimerism (a presumed souvenir from pregnancy) – enjoy half the risk of all-cause mortality compared with women test...
We previously demonstrated that women with detectable male cells in peripheral blood – male origin microchimerism (a presumed souvenir from pregnancy) – enjoy half the risk of all-cause mortality compared with women tested negative. However, such differences are vulnerable to confounding. Also, it is unknown whether better survival in women vs. men is confined to women testing male origin microchimerism positive. In this updated analysis, we first compared the survival of positive and negative women using prognostic score weighing to minimize potential confounding. Next, we compared the survival of women tested positive and negative for male origin microchimerism to men. Women (n = 766) and men (n = 1,000) from the Diet, Cancer, and Health cohort aged 50–64 years in 1993–1997 were followed until 2017 for all-cause mortality in national Danish registers. Based on predictors of death, we calculated prognostic scores for all women and compared mortality according to male origin microchimerism status by prognostic score weighted Cox regression adjusting for potential confounding. Next, we compared mortality across positive/negative women and men. Women who tested male origin microchimerism positive versus negative had a 50% lower mortality rate (adjusted HR = 0.50 [95% CI 0.32–0.77]). Compared with men, women who tested positive had a 51% lower mortality rate (HR = 0.49 [95% confidence interval (CI) 0.38–0.61]), whereas women who tested negative had a similar rate (HR = 0.83 [95% CI 0.63–1.09]). Women who tested positive for male origin microchimerism lived longer than their counterparts who tested negative, who appeared to have a similar survival pattern to that of men.
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