The Rotterdam Study
The Rotterdam Study, also known as Erasmus Rotterdam Gezondheid Onderzoek (ERGO) in Dutch, is a large-scale, ongoing cohort study based in Rotterdam, the Netherlands. Initiated in 1990, its primary objective is to investigate the determinants of chronic diseases in the elderly. The study is designed to help understand how certain factors influence the aging process and the development of diseases that are prevalent among older adults.
Participants in the Rotterdam Study are residents of Ommoord, a district in Rotterdam, who were aged 55 years or older at the start of the study. The initial cohort (RS-I) consisted of 7,983 participants enrolled between 1990 and 1993. Subsequent extensions included additional cohorts: RS-II beginning in 2000 with 3,011 participants, RS-III starting in 2006 with 3,932 participants, and RS-IV starting in 2016 with 3,005 participants, all recruited from the same geographic area using similar inclusion criteria.
The sampling strategy is a community-based approach, where all inhabitants of the district within the eligible age range are invited to participate. This strategy aims to provide a representative sample of the elderly population in terms of age, gender, and health status, thereby allowing the findings to be generalized to similar populations.
Research conducted within the Rotterdam Study covers a broad spectrum of topics related to aging, including cardiovascular, neurological, endocrinological, ophthalmological, psychiatric, and locomotor disorders. The study’s comprehensive and integrative approach allows for the exploration of multimorbidity and complex interactions between various health factors.
Specifically, concerning the locomotor sector, the Rotterdam Study places a significant focus on conditions such as osteoporosis, osteoarthritis, and other musculoskeletal disorders. It examines the epidemiology and risk factors associated with these conditions, their progression, and their impact on the quality of life. Examinations such as X-rays, DXA, pqCT, mechanograph and dynamometer are utilized to assess bone, joint health, mobility and physical capabilities.
Overall, the Rotterdam Study’s long-term follow-up and extensive biobanking of biological samples enable detailed genetic, molecular, and epidemiological research. This rich data source provides a foundation for developing preventive strategies and therapeutic interventions aimed at reducing the burden of chronic diseases in the elderly population.
Publications
Association between gut microbiome profiles and host metabolic health across the life course: a population-based study
Association between gut microbiome profiles and host metabolic health across the life course: a population-based study
Abstract
Osteoporosis is the most prevalent bone condition in the ageing population. This systemic disease is characterized by microarchitectural deterioration of bone, leading to increased fracture risk. In the past 15 years, genome-wide association studies (GWAS), have pinpointed hundreds of loci associated with bone mineral density (BMD), helping elucidate the underlying molecular mechanisms and genetic architecture of fracture risk. However, the challenge remains in pinpointing causative genes driving GWAS signals as a pivotal step to drawing the translational therapeutic roadmap. Recently, a skull BMD-GWAS uncovered an intriguing intersection with craniosynostosis, a congenital anomaly due to premature suture fusion in the skull. Here, we recapitulate the genetic contribution to both osteoporosis and craniosynostosis, describing the biological underpinnings of this overlap and using zebrafish models to leverage the functional investigation of genes associated with skull development and systemic skeletal homeostasis.
Keywords: bone mineral density; craniosynostosis; fractures; genome-wide association studies; osteoporosis; zebrafish.
For more information on this article in Pure, click here.
Sarcopenia and Sarcopenic Obesity and Mortality Among Older People
High Bone Mass Disorders: New Insights From Connecting the Clinic and the Bench
- DOI: 10.1002/jbmr.4715
Abstract
Monogenic high bone mass (HBM) disorders are characterized by an increased amount of bone in general, or at specific sites in the skeleton. Here, we describe 59 HBM disorders with 50 known disease-causing genes from the literature, and we provide an overview of the signaling pathways and mechanisms involved in the pathogenesis of these disorders. Based on this, we classify the known HBM genes into HBM (sub)groups according to uniform Gene Ontology (GO) terminology. This classification system may aid in hypothesis generation, for both wet lab experimental design and clinical genetic screening strategies. We discuss how functional genomics can shape discovery of novel HBM genes and/or mechanisms in the future, through implementation of omics assessments in existing and future model systems. Finally, we address strategies to improve gene identification in unsolved HBM cases and highlight the importance for cross-laboratory collaborations encompassing multidisciplinary efforts to transfer knowledge generated at the bench to the clinic. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Keywords:ANABOLICS; ANIMAL MODELS; CELL/TISSUE SIGNALING; DISEASES AND DISORDERS OF/RELATED TO BONE; GENETIC ANIMAL MODELS; GENETIC RESEARCH; PARACRINE PATHWAYS; THERAPEUTICS.
For more information on this article in Pure, click here.
Association between BMD and coronary artery calcification: an observational and Mendelian randomization study
Association between BMD and coronary artery calcification: an observational and Mendelian randomization study
- DOI: 10.1093/jbmr/zjae022
Abstract
Observational studies have reported inconsistent associations between bone mineral density (BMD) and coronary artery calcification (CAC). We examined the observational association of BMD with CAC in 2 large population-based studies and evaluated the evidence for a potential causal relation between BMD and CAC using polygenic risk scores (PRS), 1- and 2-sample Mendelian randomization (MR) approaches. Our study populations comprised 1414 individuals (mean age 69.9 yr, 52.0% women) from the Rotterdam Study and 2233 individuals (mean age 56.5 yr, 50.9% women) from the Framingham Heart Study with complete information on CAC and BMD measurements at the total body (TB-), lumbar spine (LS-), and femoral neck (FN-). We used linear regression models to evaluate the observational association between BMD and CAC. Subsequently, we compared the mean CAC across PRSBMD quintile groups at different skeletal sites. In addition, we used the 2-stage least squares regression and the inverse variance weighted (IVW) model as primary methods for 1- and 2-sample MR to test evidence for a potentially causal association. We did not observe robust associations between measured BMD levels and CAC. These results were consistent with a uniform random distribution of mean CAC across PRSBMD quintile groups (P-value > .05). Moreover, neither 1- nor 2-sample MR supported the possible causal association between BMD and CAC. Our results do not support the contention that lower BMD is (causally) associated with an increased CAC risk. These findings suggest that previously reported epidemiological associations of BMD with CAC are likely explained by unmeasured confounders or shared etiology, rather than by causal pathways underlying both osteoporosis and vascular calcification processes.
Keywords:BMD; Mendelian randomization; coronary artery calcification; osteoporosis; polygenic risk score.
For more information on this article in Pure, click here.
The Rotterdam Study. Design update and major findings between 2020 and 2024
The Rotterdam Study. Design update and major findings between 2020 and 2024
Abstract
The Rotterdam Study is a population-based cohort study, started in 1990 in the district of Ommoord in the city of Rotterdam, the Netherlands, with the aim to describe the prevalence and incidence, unravel the etiology, and identify targets for prediction, prevention or intervention of multifactorial diseases in mid-life and elderly. The study currently includes 17,931 participants (overall response rate 65%), aged 40 years and over, who are examined in-person every 3 to 5 years in a dedicated research facility, and who are followed-up continuously through automated linkage with health care providers, both regionally and nationally. Research within the Rotterdam Study is carried out along two axes. First, research lines are oriented around diseases and clinical conditions, which are reflective of medical specializations. Second, cross-cutting research lines transverse these clinical demarcations allowing for inter- and multidisciplinary research. These research lines generally reflect subdomains within epidemiology. This paper describes recent methodological updates and main findings from each of these research lines. Also, future perspective for coming years highlighted.
Keywords:Biomarkers; Cancer and related diseases; Cardiovascular diseases; Cohort study; Dermatological diseases; Endocrine diseases; Epidemiologic methods; Genetic and molecular epidemiology; Liver diseases; Neurological diseases; Nutrition and lifestyle epidemiology; Oncology; Ophthalmic diseases; Otolaryngological diseases; Pharmacoepidemiology; Population imaging; Psychiatric diseases; Renal diseases; Respiratory diseases; Responsible research; Risk factors.
For more information on this article in Pure, click here.
Bone mineral density and the risk of incident dementia: A meta-analysis
Bone mineral density and the risk of incident dementia: A meta-analysis
- DOI: 10.1111/jgs.18638
Abstract
Background: It is not known whether bone mineral density (BMD) measured at baseline or as the rate of decline prior to baseline (prior bone loss) is a stronger predictor of incident dementia or Alzheimer’s disease (AD).
Methods: We performed a meta-analysis of three longitudinal studies, the Framingham Heart Study (FHS), the Rotterdam Study (RS), and the Rush Memory and Aging Project (MAP), modeling the time to diagnosis of dementia as a function of BMD measures accounting for covariates. We included individuals with one or two BMD assessments, aged ≥60 years, and free of dementia at baseline with follow-up available. BMD was measured at the hip femoral neck using dual-energy X-ray absorptiometry (DXA), or at the heel calcaneus using quantitative ultrasound to calculate estimated BMD (eBMD). BMD at study baseline (“baseline BMD”) and annualized percentage change in BMD prior to baseline (“prior bone loss”) were included as continuous measures. The primary outcome was incident dementia diagnosis within 10 years of baseline, and incident AD was a secondary outcome. Baseline covariates included age, sex, body mass index, ApoE4 genotype, and education.
Results: The combined sample size across all three studies was 4431 with 606 incident dementia diagnoses, 498 of which were AD. A meta-analysis of baseline BMD across three studies showed higher BMD to have a significant protective association with incident dementia with a hazard ratio of 0.47 (95% CI: 0.23-0.96; p = 0.038) per increase in g/cm2 , or 0.91 (95% CI: 0.84-0.995) per standard deviation increase. We observed a significant association between prior bone loss and incident dementia with a hazard ratio of 1.30 (95% CI: 1.12-1.51; p < 0.001) per percent increase in prior bone loss only in the FHS cohort.
Conclusions: Baseline BMD but not prior bone loss was associated with incident dementia in a meta-analysis across three studies.
Keywords:Alzheimer’s disease; BMD; bone loss; dementia; osteoporosis.
For more information on this article in Pure, click here.
Oral corticosteroid use and sarcopenia-related traits in older people with chronic airway disease: a population-based study
Oral corticosteroid use and sarcopenia-related traits in older people with chronic airway disease: a population-based study
Abstract
Background: Sarcopenia is characterised by two major phenotypic components: low handgrip strength (HGS) and appendicular skeletal muscle index (ASMI). Oral corticosteroid (OCS) use is an important medication for acute respiratory exacerbations in patients with COPD and asthma. However, the association of OCS and sarcopenia components in older people is largely unexplored. The aim of this study was to examine the association between OCS use and HGS or ASMI in the general population and explore interactions with chronic airway diseases.
Methods: From the population-based Rotterdam Study, 5054 participants (age 69.0±8.8 years; 56% females) were included in the cross-sectional analysis and 1324 in the longitudinal analysis. Associations between OCS and muscle strength and mass were analysed using linear regression models adjusted for age, sex, fat %, height, kidney function, smoking and comorbidities.
Results: At baseline, ever-OCS users had lower handgrip strength (β= -0.48, 95% CI -0.84- -0.12) than never-OCS users, with cumulative frequency (≥10 OCS prescriptions)-dependent effects (β= -1.25, 95% CI -2.16- -0.33). COPD ever-OCS users, but not asthma, had lower handgrip strength (β= -0.98, 95% CI -1.91- -0.06) and lower lean mass (β= -0.14, 95% CI -0.27- -0.01) than never-OCS users. After 5.6 years of follow-up in those free of sarcopenia traits at baseline, COPD ever-OCS users developed lower handgrip strength (β= -1.64, 95% CI -2.87- -0.40) with frequency (β= -3.64, 95% CI -6.57- -0.72) and duration (β= -1.51, 95% CI -2.87- -0.15) association compared to never-OCS users.
Conclusions: OCS use is associated with a decline in handgrip strength in people with COPD in a cumulative frequency and duration-dependent manner. Routine muscle examination may be necessary for patients with COPD.
For more information on this article in Pure, click here.
Association of Bone Mineral Density and Dementia: The Rotterdam Study
Association of Bone Mineral Density and Dementia: The Rotterdam Study
Abstract
Background and objectives: Low bone mineral density (BMD) and dementia commonly co-occur in older individuals, with bone loss accelerating in patients with dementia due to physical inactivity and poor nutrition. However, uncertainty persists over the extent to which bone loss already exists before onset of dementia. Therefore, we investigated how dementia risk was affected by BMD at various skeletal regions in community-dwelling older adults.
Methods: In a prospective population-based cohort study, BMD at the femoral neck, lumbar spine, and total body and the trabecular bone score (TBS) were obtained using dual-energy X-ray absorptiometry in 3,651 participants free from dementia between 2002 and 2005. Persons at risk of dementia were followed up until January 1, 2020. For analyses of the association between BMD at baseline and the risk of incident dementia, we used Cox proportional hazards regression analyses, adjusting for age, sex, educational attainment, physical activity, smoking status, body mass index, systolic and diastolic blood pressure, cholesterol level, high-density lipoprotein cholesterol, history of comorbidities (stroke and diabetes mellitus), and APOE genotype.
Results: Among the 3,651 participants (median age 72.3 ± 10.0 years, 57.9% women), 688 (18.8%) developed incident dementia during a median of 11.1 years, of whom 528 (76.7%) developed Alzheimer disease (AD). During the whole follow-up period, participants with lower BMD at the femoral neck (per SD decrease) were more likely to develop all-cause dementia (hazard ratio [HR] total follow-up 1.12, 95% CI 1.02-1.23) and AD (HRtotal follow-up 1.14, 95% CI 1.02-1.28). Within the first 10 years after baseline, the risk of dementia was greatest for groups with the lowest tertile of BMD (femoral neck BMD, HR0-10 years 2.03; 95% CI 1.39-2.96; total body BMD, HR0-10 years 1.42; 95% CI 1.01-2.02; and TBS, HR0-10 years 1.59; 95% CI 1.11-2.28).
Discussion: In conclusion, participants with low femoral neck and total body BMD and low TBS were more likely to develop dementia. Further studies should focus on the predictive ability of BMD for dementia.
For more information on this article in Pure, click here.
Younger facial looks are associate with a lower likelihood of several age-related morbidities in the middle-aged to elderly
Younger facial looks are associate with a lower likelihood of several age-related morbidities in the middle-aged to elderly
- DOI: 10.1093/bjd/ljac100
Abstract
Background: Looking older for one’s chronological age is associated with a higher mortality rate. Yet it remains unclear how perceived facial age relates to morbidity and the degree to which facial ageing reflects systemic ageing of the human body.
Objectives: To investigate the association between ΔPA and age-related morbidities of different organ systems, where ΔPA represents the difference between perceived age (PA) and chronological age.
Methods: We performed a cross-sectional analysis on data from the Rotterdam Study, a population-based cohort study in the Netherlands. High-resolution facial photographs of 2679 men and women aged 51.5-87.8 years of European descent were used to assess PA. PA was estimated and scored in 5-year categories using these photographs by a panel of men and women who were blinded for chronological age and medical history. A linear mixed model was used to generate the mean PAs. The difference between the mean PA and chronological age was calculated (ΔPA), where a higher (positive) ΔPA means that the person looks younger for their age and a lower (negative) ΔPA that the person looks older. ΔPA was tested as a continuous variable for association with ageing-related morbidities including cardiovascular, pulmonary, ophthalmological, neurocognitive, renal, skeletal and auditory morbidities in separate regression analyses, adjusted for age and sex (model 1) and additionally for body mass index, smoking and sun exposure (model 2).
Results: We observed 5-year higher ΔPA (i.e. looking younger by 5 years for one’s age) to be associated with less osteoporosis [odds ratio (OR) 0.76, 95% confidence interval (CI) 0.62-0.93], less chronic obstructive pulmonary disease (OR 0.85, 95% CI 0.77-0.95), less age-related hearing loss (model 2; B = -0.76, 95% CI -1.35 to -0.17) and fewer cataracts (OR 0.84, 95% CI 0.73-0.97), but with better global cognitive functioning (g-factor; model 2; B = 0.07, 95% CI 0.04-0.10).
Conclusions: PA is associated with multiple morbidities and better cognitive function, suggesting that systemic ageing and cognitive ageing are, to an extent, externally visible in the human face.
© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
For more information on this article in Pure, click here.
Frailty Transitions in Older Persons With Lung Function Impairment: A Population-Based Study
Frailty Transitions in Older Persons With Lung Function Impairment: A Population-Based Study
Abstract
Background: The aging population and its burden on health care systems warrant early detection of patients at risk of functional decline and mortality. We aimed to assess frailty transitions and its accuracy for mortality prediction in participants with impaired spirometry (Preserved Ratio Impaired Spirometry [PRISm] or chronic obstructive pulmonary disease [COPD]).
Methods: In participants from the population-based Rotterdam Study (mean age 69.1 ± 8.9 years), we examined whether PRISm (forced expiratory volume in 1 second [FEV1]/forced vital capacity [FVC] ≥ 70% and FEV1 < 80%) or COPD (FEV1/FVC < 70%) affected frailty transitions (progression/recovery between frailty states [robust, prefrailty, and frailty], lost to follow-up, or death) using age-, sex- and smoking state-adjusted multinomial regression models yielding odds ratios (OR). Second, we assessed the diagnostic accuracy of frailty score for predicting mortality in participants with COPD using c-statistics.
Results: Compared to participants with normal spirometry, participants with PRISm were more likely to transit from robust (OR 2.2 [1.2-4.2], p < .05) or prefrailty (OR 2.6 [1.3-5.5], p < .01) toward frailty. Participants with PRISm (OR 0.4 [0.2-0.8], p < .05) and COPD (OR 0.6 [0.4-1.0], NS) were less likely to recover from their frail state, and were more likely to progress from any frailty state toward death (OR between 1.1 and 2.8, p < .01). Accuracy for predicting mortality in participants with COPD significantly improved when adding frailty score to age, sex, and smoking status (90.5 [82.3-89.8] vs 77.9 [67.2-88.6], p < .05).
Conclusion: Participants with PRISm or COPD more often developed frailty with poor reversibility. Assessing physical frailty improved risk stratification for participants with impaired spirometry for predicting increased life years.
Keywords: Epidemiology; Frailty; Pulmonary; Resilience.
© The Author(s) 2022. Published by Oxford University Press on behalf of The Gerontological Society of America.
For more information on this article in Pure, click here.
