Population-based Prospective Cohort Research Articles

The additive interaction of healthy lifestyles and genetic susceptibility on colorectal cancer risk in prediabetes: a large population-based prospective cohort study

ObjectiveWe aimed to investigate the interrelationships among polygenic risk scores (PRS), healthy lifestyle factors (HLFs), and colorectal cancer (CRC) risk in individuals with prediabetes. To investigate whether adherence to HLFs influence CRC risk in those with elevated PRS within this specific population.MethodsData from 22,408 prediabetes participants without CRC at baseline were analyzed from the UK Biobank. HLFs were graded using healthy lifestyle scores (HLSs) and classified as favorable, intermediate, or unfavorable, while the PRS for CRC was categorized as high, medium, or low. Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for CRC risk.ResultsHigh PRS (HR: 2.36; 95% CI: 1.86–3.00) and medium PRS (HR: 1.42; 95% CI: 1.09–1.83) prediabetes were associated with increased CRC risk compared to those with low PRS. HLFs were linked to lower CRC risk in a dose–response manner, with never smoking (HR: 0.69; 95% CI: 0.57–0.84) and maintaining a healthy BMI (HR: 0.64; 95% CI: 0.49–0.82) associated with reduced CRC risk. Adherence to favorable HLFs may reduce the CRC risk in those with medium (HR: 0.51; 95% CI: 0.27–0.95) and high PRS (HR: 0.62; 95% CI: 0.39–0.99) over 15 years of follow-up. In participants with high PRS and unfavorable HLFs, the excess risk due to the additive interaction between PRS and HLFs was 1.41% (p < 0.01), especially for women (1.07%).ConclusionsThere is an additive interaction of PRS and HLFs on CRC risk in individuals with prediabetes. Adopting favorable HLFs should be integrated into the management of prediabetes individuals to reduce the risk of CRC.

Smoking-independent DNA methylation markers for lung cancer risk: External validation in a large population-based cohort study.

Smoking-associated epigenetic changes have been linked to lung cancer (LC) risk; however, the role of epigenetic alterations independent of smoking is yet to be fully understood. This study aimed to validate 16 previously reported CpG sites that are independent of smoking yet associated with LC risk within a population-based prospective cohort. Using the Infinium Methylation EPIC BeadChip kit or the Infinium HumanMethylation450K BeadChip Assay, DNA methylation (DNAm) in whole blood was assessed in four subsets (n = 736, 1027, 997, and 312) of a population-based cohort from Germany. The DNAm levels of the 16 smoking-independent CpG sites were analyzed. Hazard ratios (HRs) and their 95% confidence intervals (95% CIs) were calculated to assess associations of DNAm at the 16 CpG sites with LC risk, adjusting for multiple covariates, including smoking habits and a smoking-associated DNAm score. Over 17 years of follow-up, a total of 199 LCs were observed. Among the 16 CpGs, cg02211449 showed a negative association with LC risk (HR [95% CI] per SD increase, = 0.70 [0.63-0.78]), while cg11385536 (1.04 [1.01-1.07]), cg09736286 (1.64 [1.10-2.44]), cg19907023 (1.64 [1.01-2.66]), and cg22032485 (1.52 [1.04-2.21]) displayed positive associations with LC risk. Five of the 16 suggested smoking-independent CpGs could be externally validated as predictors of LC risk. Further research should address their potential contribution to enhanced LC risk stratification.

Normative Population-Derived Data for MRI Manifestations of Cerebral Small Vessel Disease.

Cerebral small vessel disease (SVD) is manifested on magnetic resonance imaging (MRI) by white matter hyperintensities, lacunes, microbleeds, and atrophy. While these manifestations can be part of normal aging, a high burden has been associated with cognitive impairment and vascular events. Distinguishing between normal versus abnormal SVD lesion burden in clinical practice remains complex. Our objective is to establish age- and sex-specific normative data for MRI manifestations of SVD, to support clinical assessment in individual patients. We used 11 465 MRI scans from 5402 participants of the Rotterdam Study, the Netherlands, an ongoing prospective population-based cohort since 1990, to develop percentile curves for white matter hyperintensities and brain parenchymal fraction and probability curves for the prevalence and count of lacunes and microbleeds, across ages 45 to 100 years, stratified by sex. Participants were primarily White (≈97%), with a mean age at first scan of 64.7 (range, 45.7-97.9) years, and 55.7% being female participants. For all SVD MRI manifestations, the curves demonstrated nonlinear trends, with accelerating burden with advancing age (eg, doubling of white matter hyperintensity fraction every 10 years). Regarding brain parenchymal fraction, a decline was seen earlier in male participants (≈45 years) than female participants (≈60 years) and was more pronounced in male participants over time. Female participants had slightly higher white matter hyperintensity fractions compared with male participants across all ages. Lacunes and microbleeds were more frequently found in male participants than in female participants, and microbleeds were more prevalent than lacunes. We provide comprehensive normative data for different MRI manifestations of SVD, presented as percentile and probability curves by age, stratified by sex. This can aid clinicians to actually quantify the SVD burden on an individual patient's MRI scans and detect patterns of abnormality.

Association of early-life factors with biological age acceleration and the mediating effect of social environment risks in middle-aged and older adults.

Adverse early-life events influence the health with ageing throughout the life course. However, the effects of combined early-life risks on ageing acceleration in adults and the roles of social environment risks remain unknown. To investigate associations of maternal smoking, breastfeeding and birth weight with accelerated biological age (BA), and to explore genetic-predicted effect and mediating effect of social environment risks. Population-based prospective cohort. UK Biobank. 151773 participants. We used Klemera-Doubal BA (KDM-BA), PhenoAge and leukocyte telomere length (LTL) as BA biomarkers. Associations of early-life risk factors and score with BA acceleration were estimated using linear regression models. Genetic risk score (GRS) was calculated based on genetic variations for maternal smoking and birth weight. Polysocial risk scores (PsRS) for each BA were calculated by summing the number of dichotomised social environment factors significantly associated with each of the three BA biomarkers. Maternal smoking, non-breastfeeding and low birth weight were individually associated with BA acceleration. The early-life risk score was significantly associated with accelerated KDM-BA and PhenoAge and shorter LTL. The effects of GRS on accelerated BA were in the same direction. The BA-specific PsRS mediated the accelerated KDM-BA and PhenoAge and shorter LTL by 8.37%, 22.34% and 7.90%, respectively. Our findings demonstrated a dose-dependent association of combined early-life risks with accelerated BA in middle-aged and older adults, partially mediated by social environment risks. The findings highlight the importance of early identification and surveillance of high-risk individuals for ageing acceleration during adulthood.

Triglyceride-glucose index and its additive interaction with ABCG2/SLC2A9 polygenic risk score on hyperuricemia in middle age and older adults: findings from the DLCC and BHMC study

Objective We aim to investigate the joint effect of triglyceride-glucose (TyG) index and polygenic risk scores (PRS) of urate transporter genes ABCG2 and SLC2A9 on hyperuricemia. Methods Baseline data from two prospective population-based cohort studies, including 30,453 individuals aged 50 years or older, were used to analyze the association between TyG index and hyperuricemia. A case-control study was then designed from the cohorts to investigate the interaction between genetic predisposition and TyG index on hyperuricemia among 595 matched pairs. PRS was constructed using 14 single nucleotide polymorphisms located in the ABCG2 and SLCA29 genes. Results In both sexes, higher TyG index levels were correlated with elevated serum urate (SUA) levels (p values in both sexes < 0.001). In men, per unit increase of TyG was associated with a 1.44-fold (95% confidence interval [CI]: 1.35–1.55) higher risk of hyperuricemia after adjusted for covariates. In women, this estimate was 1.69 (1.51–1.89). Demonstrated by the restrict cubic spline model, TyG index was both linearly and non-linearly associated with elevated SUA (both p values < 0.001). Association between TyG index and hyperuricemia was stronger among people with higher genetic risk, and vice versa. Compared to people with TyG < 9 and PRS < 2, the odds ratios (ORs) (95% CIs) for hyperuricemia in the TyG <9 but PRS ≥2, TyG ≥9 but PRS < 2, TyG ≥9 and PRS ≥2 groups were 3.30 (1.53–7.14), 3.16 (1.23–8.11) and 7.55 (2.76–20.65), respectively. Additive interaction was also significant, with 57.5% (30.5%–84.4%) of the excess risk attributable to the additive gene-TyG index interaction. Conclusions The impact of genetic predisposition on hyperuricemia was significantly greater among individuals with a higher TyG index. Over 50% of the increased risk can be attributed to the interaction, indicating a crucial synergy between genetic factors and TyG index when estimating hyperuricemia risk.

Association Between Intellectual Disability and Hair Cortisol Concentration in Adolescents in a Brazilian Population-Based Birth Cohort.

Children with intellectual disability (ID) usually exhibit neuroendocrine functioning impairment, such as alterations in the hypothalamic-pituitary-adrenal (HPA) neuroendocrine axis, which can result in glucocorticoid cortisol release alterations. Indeed, many studies showed a positive association between ID and cortisol concentration. However, evidence is lacking on the relationship between child neurodevelopment and cortisol levels during adolescence in population-based studies. We aimed to test the association between ID and hair cortisol concentration (HCC) during adolescence in a prospective population-based cohort. Data from 1770 individuals in the 2004 Pelotas Birth Cohort were used. ID was diagnosed at age 6 through clinical examination. Hair cortisol was measured at age 15. Association was assessed using linear regression models adjusted for sex, socio-economic factors, hair-related variables and corticosteroid use. Higher HCC were observed in individuals with ID (β: 1.120; 95% CI: 1.012, 1.241) in the analysis adjusted for sex, hair-related variables and corticosteroid use. Compared to the other aetiological groups, this was more evident in idiopathic ID. But this did not remain significant when demographics/socio-economic variables were controlled for. Children with ID, particularly those with idiopathic ID, might exhibit dysfunction in the HPA axis or experience heightened stress levels during adolescence.

Impact of Mediterranean Diet Adherence on the Incidence of New-Onset Hypertension in Adults With Obesity in Korea: A Nationwide Cohort Study.

This study investigated the association between adherence to the Mediterranean diet (MD) and new-onset hypertension (HTN) in a cohort of community-dwelling, middle-aged, older Korean individuals with obesity. We used data from the Korean Genome and Epidemiology Study, a population-based prospective cohort study. The Korean version of the MD Adherence Screener was used to evaluate compliance with the MD. The primary endpoint was the incidence of new-onset HTN. Cox proportional hazard models were used to estimate the hazard ratio (HR) and 95% confidence interval for HTN incidence with increasing MD adherence. Data from 1995 participants with obesity without HTN at baseline were analyzed. After adjusting for confounders, participants with moderate (Group 2) and high adherence (Group 3) to the MD had HRs for new-onset HTN of 0.72 (0.57-0.90) and 0.73 (0.56-0.95), respectively, compared with those with low adherence (Group 1). Sex and age differences were associated with MD adherence and HTN incidence. The association between MD adherence and HTN incidence was only significant in males and in participants aged 40-64years. There was no significant association between MD adherence and new-onset HTN in females or those aged ≥ 65years. In conclusion, this study found a significant association between adherence to the MD and a reduction in new-onset HTN in Korean adults with obesity. Considering its value and sustainability, the adoption of the MD may contribute to the prevention of new-onset HTN in populations with obesity.

Vertical Living and Longevity: Examining Mortality by Floor of Residence in an Elderly Population.

Studies investigating the potential health effects of floor of residence have reported conflicting results. In the Rotterdam Study, we examined associations between floor and mortality among elderly residents of a neighborhood of Rotterdam, the Netherlands. Participants who were high-rise residents at baseline (n = 2330) were followed for 10years, until loss to follow-up or death (N = 602). Cox proportional hazard models revealed nonlinear association of floor of residence with mortality, albeit not statistically significant across all floor categories. Compared to floors 13 and above, adjusted hazard ratios [95% confidence interval] were: 1.31 [0.89-1.95] (floors 1-2), 1.52 [1.04-2.22] (floors 3-4), 1.07 [0.73-1.57] (floors 5-6), 1.12 [0.76-1.66] (floors 7-8), 1.45 [0.96-2.18] (floors 9-10), and 1.04 [0.69-1.58] (floors 11-12). In this prospective population-based cohort of elderly adults in Rotterdam, the Netherlands, a nonlinear association was observed between floor level of residence and mortality, with stronger associations observed at lower floors compared to the highest floors.

Body Composition and Incident High-Intensity Back Pain and/or High Disability: A 10-Year Prospective Population-Based Male Cohort.

Back pain poses a significant global burden, within which individuals with more severe symptoms consume higher healthcare expenses than those with lesser back pain. Whether measures of body composition predict high-intensity back pain and/or high-disability in population-based cohorts is unknown. This study aimed to examine the association between body composition at baseline and their change in the prior 5 years (between 2001-2005 and 2006-2010) and incident high-intensity back pain and/or high-disability in long-term follow-up, 10 years later (2016-2021) in a population-based cohort of men. This study examined men with no or low-intensity back pain and disability (Graded Chronic Pain Scale) at back pain study baseline (2006-2010) within the Geelong Osteoporosis Study. Those developing high-intensity pain and/or high disability at follow-up (2016-2021) were identified. Weight, body mass index (BMI), abdominal circumferences, fat mass and lean mass (dual energy X-ray absorptiometry) were assessed prebaseline (2001-2005) and at baseline. The association of body composition at baseline and change in body composition from prebaseline to baseline with incident high-intensity pain and/or high disability at follow-up were examined using multivariable logistic regression. Of 695 participants with no or low-intensity pain and disability at baseline, 441 (62.3%) completed follow-up with a mean age of 54.3 ± 14.1 years: 37 (8.3%) developed high-intensity pain and/or high-disability, 33 (7.5%) developed high-intensity pain and 14 (3.2%) high disability. No measures of body composition at baseline were associated with incident high-intensity pain and/or high disability at follow-up in the whole population. In subgroup analysis, among men aged over 60 years, but not younger, higher lean mass was associated with decreased likelihood of high-intensity pain and/or high-disability (odds ratio [OR] 0.86, 95% confidence interval [CI] 0.76, 0.97, interaction p < 0.001). In the whole population, examination of the relationship between change in measures of body composition between prebaseline and baseline, only a one unit increase in BMI, equivalent to 3.1-kg weight gain, was associated with increased incident high disability (OR 1.63, 95% CI 1.06, 2.51). In a population-based sample, without severe back pain and disability, in older men aged ≥60 years, higher lean mass was protective of incident high-intensity pain and/or high disability. An increase in BMI, over 5 years, equivalent to 3.1-kg weight gain, was associated with incident back pain related high disability 10 years later. These results demonstrate another detrimental consequence of weight gain and highlight the importance of maintaining muscle mass in older men.

Investigating the relationship between liver health status with coffee and tea consumption in participants referred to the Rafsanjan Cohort study in Iran

Coffee, tea and caffeinated foods are popular in the world due to their high amount of caffeine, which are consumed daily by people in large quantities, and their effects on the body, especially the liver, are somewhat unknown, so this study was done with the aim of relationship between coffee and tea consumption and dietary intake of Caffeine on the serum liver enzymes and lipid profile. In this cross-sectional study the information of 8889 participants aged 35–70 years who referred to the Rafsanjan Cohort Study (RCS), a population-based prospective cohort that is a part of the Prospective epidemiological research studies in Iran (PERSIAN), was used. Demographic characteristics, medical history, consumption of coffee and tea, caffeine intake, and laboratory tests were collected. Dichotomous logistics regression models were used using crude and adjusted models to investigate the relationship between coffee, tea consumption, and caffeine intake with liver enzymes and lipid profile. Out of 8889 participants 4678 (52.6%) were female and 4211 (47.4%) were male. In older people, especially men, the consumption of tea and coffee increased and has a direct relationship with the abnormality of total cholesterol (TC) (OR 1.14; 95% CI 1.01 to 1.29). Also, it was observed that increased abnormal Alkaline phosphatase (ALP) (OR 1.22; 95% CI 1.01 to 1.52) and decreased abnormal serum glutamic-oxaloacetic transaminase (SGOT) (OR 0.65; 95% CI 0.46 to 0.93) were significantly associated with a high intake of caffeine. The other variables related to lipid profile and liver enzymes increased with increasing consumption of coffee, tea and intake of caffeine in participants, but did not show a significant increase. A high intake of caffeine and coffee and tea can have adverse effects on some liver enzymes and blood factors. Therefore, care should be taken when using these materials.

School well-being in primary school children with chronic illness. A prospective cohort study.

Children with chronic illness perform poorer at school, and school well-being (SWB) may mediate this association. We investigated the association between chronic illness and three domains of SWB in children in first grade. Data from a German population-based prospective cohort study were used. Children with chronic illness were identified via their preschool health examination and follow-up parent surveys during first grade. Children were grouped as either (i) having current special health care needs (SHCN), (ii) having at least one physician diagnosis of a chronic illness but no current SHCN, or (iii) being healthy. SWB was assessed at the end of first grade and measured by the Questionnaire for the Assessment of Emotional and Social School Experiences of First and Second Grade Primary School Children. Based on SWB theory and previous frameworks, the following subscales were used: School-Related Self-Concept, Social Integration, and Joy of Learning. The sum score for each subscale was converted into area-transformed T-values (mean 50 and standard deviation 10). Associations between chronic illness groups and SWB subscales were investigated by multivariable linear regression models. Effect estimates were adjusted for potential confounding variables and standardized mean differences (SMD) were calculated. Of the 1,490 children included, 15% had current SHCN and 37% had a physician diagnosis of a chronic illness but no current SHCN. Compared to healthy children, children with SHCN had lower scores for the School-Related Self-Concept and the Joy of Learning subscale (SMD -0.18 for both) but not for the Social Integration subscale. In contrast, children with a chronic condition but no SHCN had lower scores only for the Social Integration subscale (SMD -0.12). Primary school students with a chronic illness with or without SHCN have lower SWB in some domains compared to their healthy peers. SWB may be a mediator in the association between chronic illness and poor school performance.

Methodology for Biological Sample Collection, Processing, and Storage in the Newcastle 1000 Pregnancy Cohort: Protocol for a Longitudinal, Prospective Population-Based Study in Australia.

Research in the developmental origins of health and disease provides compelling evidence that adverse events during the first 1000 days of life from conception can impact life course health. Despite many decades of research, we still lack a complete understanding of the mechanisms underlying some of these associations. The Newcastle 1000 Study (NEW1000) is a comprehensive, prospective population-based pregnancy cohort study based in Newcastle, New South Wales, Australia, that will recruit pregnant women and their partners at 11-14 weeks' gestation, with assessments at 20, 28, and 36 weeks; birth; 6 weeks; and 6 months, in order to provide detailed data about the first 1000 days of life to investigate the developmental origins of noncommunicable diseases. The study aims to provide a longitudinal multisystem approach to phenotyping, supported by robust clinical data and collection of biological samples in NEW1000. This manuscript describes in detail the large variety of samples collected in the study and the method of collection, storage, and utility of the samples in the biobank, with a particular focus on incorporation of the samples into emerging and novel large-scale "-omics" platforms, including the genome, microbiome, epigenome, transcriptome, fragmentome, metabolome, proteome, exposome, and cell-free DNA and RNA. Specifically, this manuscript details the methods used to collect, process, and store biological samples, including maternal, paternal, and fetal blood, microbiome (stool, skin, vaginal, oral), urine, saliva, hair, toenail, placenta, colostrum, and breastmilk. Recruitment for the study began in March 2021. As of July 2024, 1040 women and 684 partners were enrolled, with 922 infants born. The NEW1000 biobank contains 24,357 plasma aliquots from ethylenediaminetetraacetic acid (EDTA) tubes, 5284 buffy coat aliquots, 4000 plasma aliquots from lithium heparin tubes, 15,884 blood serum aliquots, 2977 PAX RNA tubes, 26,595 urine sample aliquots, 2280 fecal swabs, 17,687 microbiome swabs, 2356 saliva sample aliquots, 1195 breastmilk sample aliquots, 4007 placental tissue aliquots, 2680 hair samples, and 2193 nail samples. NEW1000 will generate a multigenerational, deeply phenotyped cohort with a comprehensive biobank of samples relevant to a large variety of analyses, including multiple -omics platforms. DERR1-10.2196/63562.

Abstract 4113411: Long Term Outcomes of Hypertension and Antihypertensive Drugs in Young Healthy Adults: A Nationwide Population-based Prospective Cohort Study in Korea

Background: Long term follow-up data on elevated blood pressure (BP) or antihypertensive drugs in young adults are scarce. The effect of hypertension (HTN) and antihypertensive medications on the cardiovascular disease incidence in young healthy adults (20~45 years) was analyzed using a large-scale population medical use database in Korea. Methods: In total, 4,590,597 young Korean adults without comorbidities who underwent regular health examination were included in this study. They were stratified into four groups according to their BP (optimal BP, normal BP, high normal BP, and HTN). The primary outcome was a composite of the incidence of myocardial infarction and ischemic and hemorrhagic stroke, obtained by tracking the medical use data of the first-ever ICD-10 codes. Subgroup analysis was conducted by categorizing the HTN group into two subgroups according to the prescription ratios of the antihypertensive drugs during the follow-up period. Results: The average age was 33.8 years and median follow-up duration was 15.9 years. HTN elevated the incidence risk of major cardiovascular disease by 2.16 times compared to that of the optimal BP group. Dyslipidemia and HTN were the most dominant risk factors for myocardial infarction and stroke, respectively. In the subgroup analysis, antihypertensive medications decreased the incidence of cardiovascular disease by 70% in all diseases. Conclusions: Cardiovascular risk factors, including HTN, contribute to major cardiovascular disease incidence in young adults. The antihypertensive medications decreased the major cardiovascular disease incidence estimates.

An Ensemble Deep Learning Algorithm for Structural Heart Disease Screening Using Electrocardiographic Images: PRESENT SHD.

Identifying structural heart diseases (SHDs) early can change the course of the disease, but their diagnosis requires cardiac imaging, which is limited in accessibility. To leverage images of 12-lead ECGs for automated detection and prediction of multiple SHDs using an ensemble deep learning approach. We developed a series of convolutional neural network models for detecting a range of individual SHDs from images of ECGs with SHDs defined by transthoracic echocardiograms (TTEs) performed within 30 days of the ECG at the Yale New Haven Hospital (YNHH). SHDs were defined based on TTEs with LV ejection fraction <40%, moderate-to-severe left-sided valvular disease (aortic/mitral stenosis or regurgitation), or severe left ventricular hypertrophy (IVSd > 1.5cm and diastolic dysfunction). We developed an ensemble XGBoost model, PRESENT-SHD, as a composite screen across all SHDs. We validated PRESENT-SHD at 4 US hospitals and a prospective population-based cohort study, the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), with concurrent protocolized ECGs and TTEs. We also used PRESENT-SHD for risk stratification of new-onset SHD or heart failure (HF) in clinical cohorts and the population-based UK Biobank (UKB). The models were developed using 261,228 ECGs from 93,693 YNHH patients and evaluated on a single ECG from 11,023 individuals at YNHH (19% with SHD), 44,591 across external hospitals (20-27% with SHD), and 3,014 in the ELSA-Brasil (3% with SHD). In the held-out test set, PRESENT-SHD demonstrated an AUROC of 0.886 (0.877-894), sensitivity of 90%, and specificity of 66%. At hospital-based sites, PRESENT-SHD had AUROCs ranging from 0.854-0.900, with sensitivities and specificities of 93-96% and 51-56%, respectively. The model generalized well to ELSA-Brasil (AUROC, 0.853 [0.811-0.897], sensitivity 88%, specificity 62%). PRESENT-SHD performance was consistent across demographic subgroups and novel ECG formats. A positive PRESENT-SHD screen portended a 2- to 4-fold higher risk of new-onset SHD/HF, independent of demographics, comorbidities, and the competing risk of death across clinical sites and UKB, with high predictive discrimination. We developed and validated PRESENT-SHD, an AI-ECG tool identifying a range of SHD using images of 12-lead ECGs, representing a robust, scalable, and accessible modality for automated SHD screening and risk stratification. Screening for structural heart disorders (SHDs) requires cardiac imaging, which has limited accessibility. To leverage 12-lead ECG images for automated detection and prediction of multiple SHDs, we developed PRESENT-SHD, an ensemble deep learning model. PRESENT-SHD demonstrated excellent performance in detecting SHDs across 5 US hospitals and a population-based cohort in Brazil. The model successfully predicted the risk of new-onset SHD or heart failure in both US clinical cohorts and the community-based UK Biobank. By using ubiquitous ECG images to predict a composite outcome of multiple SHDs, PRESENT-SHD establishes a scalable paradigm for cardiovascular screening and risk stratification.

Physical Activity and All-Cause Mortality by Age in 4 Multinational Megacohorts

Physical activity (PA) guidelines recommend the same amount of PA through adulthood to live longer. To explore whether there is an age-dependent association between PA and all-cause mortality and to investigate the age-dependent associations between other modifiable health factors (high educational level, not smoking, not regularly consuming alcohol, healthy body weight, and living without hypertension and diabetes) and mortality. This cohort study used a pooled analysis of 4 population-based prospective cohorts (National Health Interview Survey, 1997-2018; UK Biobank, 2006-2010; China Kadoorie Biobank, 2004-2008; and Mei Jau, 1997-2016). Data were analyzed from June 2022 to September 2024. Self-reported leisure-time PA. The primary outcome was deaths identified through follow-up linkage to national death registries. Analyses were performed for the total sample and by age groups (20-29, 30-39, 40-49, 50-59, 60-69, 70-79, and ≥80 years). Cox proportional hazards regression models with stratification by study were used to calculate mortality hazard ratios and their 95% CIs for the pooled dataset and by age group. A heterogeneous sample of 2 011 186 individuals (mean [SD] age, 49.1 [14.3] years; age range, 20-97 years; 1 105 581 women [55.0%]) were included. After a median (IQR) follow-up of 11.5 (9.3-13.5) years, 177 436 deaths occurred. The association between PA and mortality in the total sample showed a nonlinear dose-response pattern, but age modified this association (P for interaction <.001); PA was consistently associated with a lower risk of mortality across all age groups, but the reduction in risk was greater in older vs younger age groups, especially at high levels of PA. The hazard ratio for mortality associated with meeting the recommended PA in the total sample was 0.78 (95% CI, 0.77-0.79). This inverse association between meeting PA recommendations and mortality was somewhat greater as age increased (P for interaction <.001). Age also modified the associations of the other modifiable health factors with mortality (all P for interaction <.001), but the magnitude of associations was greater in younger vs older age groups. In this pooled analysis of cohort studies, the association between PA and mortality risk remained consistent across the adult lifespan, which contrasts with other modifiable health factors, for which associations with mortality risk diminished with age. Given these findings, the promotion of regular PA is essential at all stages of adult life.

Associations Between Atherosclerosis and Subsequent Cognitive Decline: A Prospective Cohort Study.

This study aimed to examine whether baseline atherosclerosis was associated with subsequent short-term domain-specific cognitive decline. This research was based on the BRAVE (Beijing Research on Aging and Vessel) study, a population-based prospective cohort study of adults aged 40 to 80 years, free of dementia. At baseline (wave 1, 2019), cognitive assessments and atherosclerosis measures, including carotid intima-media thickness, carotid plaques, coronary artery calcification, and brachial-ankle pulse wave velocity were conducted. Cognitive function was reassessed in wave 2 (2022-2023) using linear mixed models for analysis. A total of 932 participants (63.7% women; mean age, 60.0±6.9 years) were included. Compared with the lowest tertile of carotid intima-media thickness, carotid plaques, and brachial-ankle pulse wave velocity, or a coronary artery calcification score=0, the highest tertile of carotid intima-media thickness (β=-0.065 SD/y [95% CI, -0.112 to -0.017]; P=0.008), carotid plaques (β=-0.070 SD/y [95% CI, -0.130 to -0.011]; P=0.021), and brachial-ankle pulse wave velocity (β=-0.057 SD/y [95% CI, -0.105 to -0.010]; P=0.018), and a coronary artery calcification score≥400 (β=-0.081 SD/y [95% CI, -0.153 to -0.008]; P=0.029) were significantly associated with a faster decline in semantic fluency after multivariable adjustment. Moreover, greater carotid intima-media thickness, coronary artery calcification, and brachial-ankle pulse wave velocity were significantly associated with a faster decline in global cognition. More significant atherosclerosis was associated with faster semantic fluency and global cognition declines.

Cancer incidence following non-neoplastic medical conditions: a prospective population-based cohort study.

Many non-neoplastic diseases have been established to be tumorigenic, and cancers are sometimes misdiagnosed as non-neoplastic diseases. We conducted a comprehensive registry-based study of site-specific cancer diagnosis risk following the diagnosis of any preceding medical condition (PMC) encoded by the International Classification of Diseases (ICD)-10 classification. We analyzed healthcare data and cancer data for a random population-based sample of 2.5 million individuals living in Finland on January 1, 2000. Hazard ratios for each PMC and cancer pair were estimated using piecewise constant hazard regression models. P-values were corrected for multiple testing with the Bonferroni method. Several lifestyle-related PMCs were associated with the risk of cancer diagnosis, exemplified by chronic obstructive pulmonary disease and subsequent lung cancer diagnosis risk (female hazard ratio [HR] = 9.91, 95% confidence interval [CI]: 9.18-19.7, p-adj. < 0.0001; male HR = 5.69, 95% CI: 5.43-5.96, p-adj. < 0.0001). Diagnosis risk of ill-defined cancers appeared to increase following diagnosis of Alzheimer's disease (AD). We identified rare PMCs of potential interest. A considerable proportion of the statistically significant associations were explainable by tobacco smoking and alcohol use. The enrichment of ill-defined cancer diagnoses in persons with AD, together with the overall inverse association between AD and cancer, may reflect underdiagnosis of cancer in this patient population. Our results provide a useful resource for research on the prevention and early detection of cancer.

Association between dietary omega-3 fatty acid intake and all-cause mortality in patients with osteoarthritis: a population-based prospective cohort study

A correlation between omega-3 polyunsaturated fatty acids (omega-3 PUFAs) and osteoarthritis (OA) incidence has been established, but research on the long-term outlook of OA patients remains limited. This study investigates the association between omega-3 PUFA intake and the risk of all-cause and cardiovascular (CV) mortality in the U.S. OA population. A cohort of 3,467 OA patients from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018 was studied. Cox proportional hazards regression models, Kaplan-Meier curves, and subgroup analyses were used to evaluate the relationship between omega-3 PUFA intake and mortality. The dose-response relationship was examined using a restricted cubic spline (RCS) model. Among the 3,467 OA patients, there were 459 all-cause deaths and 175 CV deaths. Omega-3 PUFAs were significantly negatively correlated with all-cause mortality (95% CI: 0.59–0.93, p = 0.011) but not with CV mortality (95% CI: 0.29–1.04, p = 0.056). Higher omega-3 PUFA intake was associated with a 49% decrease in all-cause mortality. Kaplan-Meier curves showed lower all-cause mortality rates in those with higher omega-3 PUFA intake. The inverse correlation was more pronounced among individuals living with a partner. The dose-response analysis indicated a linear negative relationship between omega-3 PUFA intake and all-cause mortality. Increased intake of omega-3 PUFAs is associated with a decreased risk of all-cause mortality in OA patients.

Taiso practice and risk of functional disability and dementia among older adults in Japan: The JAGES cohort study

BackgroundTaiso is a Japanese term encompassing meanings akin to calisthenics. Taiso is a widely used exercise program in Japan but whether it prevents functional disability and dementia remains unclear. This study aimed to elucidate the association between practicing Taiso, especially focusing on the well-known Radio-Taiso, and functional disability and dementia in older adults in Japan. MethodsThis population-based prospective cohort study used data from the Japan Gerontological Evaluation Study (JAGES). The participants were 18,016 people aged 65 years or older who resided in 19 municipalities in Japan and were not certified as needing long-term care at the start of follow-up. The outcomes were all functional disability, moderate-to-severe functional disability, and dementia, during an average of 5.3 years of follow-up. Four groups were created based on type of Taiso practice (None, Radio-Taiso only, Other Taiso only, or Both). The Cox proportional hazards model adjusted for age, sex, equivalized income, educational attainment, household composition, employment status, diseases requiring treatment, activities of daily living, depression, cognitive impairment, and walking duration. ResultsThe analysis included data from 11,219 individuals. The mean age of respondents was 74.2 years and 46.3% were men. Compared with the no-practice group, the Other Taiso only group showed a notably decreased risk of all functional disability (hazard ratio [95% CI] 0.87 [0.78–0.96]). The Other Taiso only group was associated with a significant reduction in the hazard ratio for moderate-to-severe functional disability (0.81 [0.70–0.93]). Decreases in the hazard ratio for dementia were also observed in the Radio-Taiso only (0.82 [0.68–0.9998]) and Other Taiso only groups (0.81 [0.70–0.93]). ConclusionsPracticing Taiso, including Radio-Taiso, may reduce the risk of dementia in older adults, while practicing other types of Taiso may reduce the risk of functional disability.

Association of dietary choline intake with incidence of dementia, Alzheimer disease, and mild cognitive impairment: a large population-based prospective cohort study

Background- ObjectiveThe objective of this study was to explore the associations between dietary choline intake and the incidence of dementia, Alzheimer disease (AD), mild cognitive impairment (MCI), and current cognitive performance in the United Kingdom Biobank cohort. MethodsDietary choline intake was categorized into quartiles of consumption based on 24-h dietary recalls, with units expressed as milligrams per day. Diagnoses of dementia, AD, and MCI were identified using the International Classification of Diseases (ICD-9/10) codes. Current cognitive performance was assessed via the computerized touchscreen interface. After adjusting for sociodemographic factors, dietary and lifestyle behaviors, and comorbid conditions, Cox proportional hazards regression, logistic regression, and restricted cubic splines were used to analyze the association between choline intake and dementia or cognitive performance. ResultsAmong 125,594 participants (55.8% female), with a mean age of 56.1 y (range: 40–70 years) at baseline and a median follow-up of 11.8 y, 1103 cases of dementia (including 385 AD and 87 cases of MCI) were recorded. U-shaped associations were observed between choline intake and dementia and AD. Participants in the 2nd quartile of total choline intake had lower risks than those in the lowest quartile, with HR of 0.80 (95% CI: 0.67, 0.96) for dementia and 0.76 (95% CI: 0.58, 1.00) for AD. Moderate intake of choline derivative, including free choline (HR, 0.77; 95%CI, 0.65, 0.92), phosphatidylcholine (HR 0.82; 95% CI: 0.68, 0.98), sphingomyelin (HR 0.82; 95% CI: 0.69, 0.98) and glycerophosphocholine (HR 0.83; 95% CI: 0.70, 1.00), were associated with a 17%–23% lower odds of dementia. Additionally, moderate total choline intake was associated with an 8%–13% lower odds of poor cognitive performance in visual attention (OR: 0.92; 95% CI: 0.86, 0.99), fluid intelligence (OR: 0.87; 95% CI: 0.82, 0.92), and complex processing speed (OR: 0.90; 95% CI: 0.84, 0.95). ConclusionsIn conclusion, our findings suggest that moderate dietary choline intake, ranging from 332.89 mg/d to 353.93 mg/d, is associated with lower odds of dementia and better cognitive performance.