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We examined the association of baseline serum 25-hydroxyvitamin D (25(OH)D) with change in weight and total body fat in a cohort of community-dwelling older adults from Southern Germany. A total of 735 participants of the population-based KORA-Age Study (2009-2012), aged 65-90 years, were followed for 2.9 [+ or -]0.1 years. Body fat was assessed with bioelectrical impedance analysis. Linear and multinomial logistic models, adjusted for baseline covariables, were used to examine the association of 25(OH)D with percentage weight and body fat change during follow-up. 25(OH)D levels were not associated with overall weight change or body fat loss. Higher 25(OH)D levels were associated with a lower likelihood of having gained > 3% of body fat in women but not in men. As we cannot exclude residual confounding by outdoor physical activity and diet, our results are not sufficient to support a causal role of 25(OH)D in the etiology of obesity in Caucasian older adults. doi:10.1038/ejcn.2015.89; published online 22 July 2015, INTRODUCTION In older adults, obesity is associated with severe health consequences. (1) As weight loss, however, is only restrictively recommended to this age group, as it may have adverse effects [...]

Objective Test the feasibility of the modified telephone interview for cognitive status (TICS-m) as a screening tool to detect cognitive impairment in a population-based sample of older subjects. Methods Data were collected from 3,578 participants, age 65-94 years, of the KORA-Age study. We used analysis of covariance to test for significant sex, age and educational differences in raw TICS-m scores. Internal consistency was analysed by assessing Cronbach's alpha. Correction for education years was undertaken, and participants were divided in three subgroups following validated cut-offs. Finally, a logistic regression was performed to determine the impact of sex on cognition subgroups. Results Internal consistency of the TICS-m was 0.78. Study participants needed approximately 5.4 min to complete the interview. Lower raw TICS-m scores were associated with male sex, older age and lower education (all p < 0.0001). After correction for education years, 2,851 (79%) had a non-impaired cognitive status (score >31). Male sex was independently associated with having a score equal to or below 27 and 31 (OR = 1.9, 95%CI 1.4-2.5 and OR = 1.5, 95%CI 1.2-1.7, respectively). Conclusions The TICS-m is a feasible questionnaire for community-dwelling older adults with normal cognitive function or moderate cognitive impairment. Lower cognitive performance was associated with being a man, being older, and having fewer years of formal education. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Molecular analytics increasingly utilize machine learning (ML) for predictive modeling based on data acquired through molecular profiling technologies. However, developing robust models that accurately capture physiological phenotypes is challenged by the dynamics inherent to biological systems, variability stemming from analytical procedures, and the resource-intensive nature of obtaining sufficiently representative datasets. Here, we propose and evaluate a new method: Contextual Out-of-Distribution Integration (CODI). Based on experimental observations, CODI generates synthetic data that integrate unrepresented sources of variation encountered in real-world applications into a given molecular fingerprint dataset. By augmenting a dataset with out-of-distribution variance, CODI enables an ML model to better generalize to samples beyond the seed training data, reducing the need for extensive experimental data collection. Using three independent longitudinal clinical studies and a case-control study, we demonstrate CODI's application to several classification tasks involving vibrational spectroscopy of human blood. We showcase our approach's ability to enable personalized fingerprinting for multiyear longitudinal molecular monitoring and enhance the robustness of trained ML models for improved disease detection. Our comparative analyses reveal that incorporating CODI into the classification workflow consistently leads to increased robustness against data variability and improved predictive accuracy., (© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.)

Background: Loss to follow-up in long-term epidemiological studies is well-known and often substantial. Consequently, there is a risk of bias to the results. The motivation to take part in an epidemiological study can change over time, but the ways to minimize loss to follow-up are not well studied. The Citizen Science approach offers researchers to engage in direct discussions with study participants and to integrate their opinions and requirements into cohort management., Methods: Guided group discussions were conducted with study participants from the KORA cohort in the Augsburg Region in Germany, established 40 years ago, as well as a group of independently selected citizens. The aim was to look at the relevant aspects of health studies with a focus on long-term participation. A two-sided questionnaire was developed subsequently in a co-creation process and presented to 500 KORA participants and 2,400 employees of the research facility Helmholtz Munich., Results: The discussions revealed that altruistic motivations, (i.e. supporting research and public health), personal benefits (i.e. a health check-up during a study examination), data protection, and information about research results in layman's terms were crucial to ensure interest and long-term study participation. The results of the questionnaire confirmed these aspects and showed that exclusively digital information channels may be an obstacle for older and less educated people. Thus, paper-based media such as newsletters are still important., Conclusions: The findings shed light on cohort management and long-term engagement with study participants. A long-term health study needs to benefit public and individual health; the institution needs to be trustworthy; and the results and their impact need to be disseminated in widely understandable terms and by the right means of communication back to the participants., (© 2024. The Author(s).)

Infrared spectroscopy is a powerful technique for probing the molecular profiles of complex biofluids, offering a promising avenue for high-throughput in vitro diagnostics. While several studies showcased its potential in detecting health conditions, a large-scale analysis of a naturally heterogeneous potential patient population has not been attempted. Using a population-based cohort, here we analyze 5,184 blood plasma samples from 3,169 individuals using Fourier transform infrared (FTIR) spectroscopy. Applying a multi-task classification to distinguish between dyslipidemia, hypertension, prediabetes, type 2 diabetes, and healthy states, we find that the approach can accurately single out healthy individuals and characterize chronic multimorbid states. We further identify the capacity to forecast the development of metabolic syndrome years in advance of onset. Dataset-independent testing confirms the robustness of infrared signatures against variations in sample handling, storage time, and measurement regimes. This study provides the framework that establishes infrared molecular fingerprinting as an efficient modality for populational health diagnostics., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The reduction of myocardial infarction (MI) and narrowing the gap between the populations with and without diabetes are important goals of diabetes care. We analyzed time trends for sex-specific incidence rates (IR) of first MI (both non-fatal MI and fatal MI) as well as separately for first non-fatal MI and fatal MI in the population with and without diabetes., Methods: Using data from the KORA myocardial infarction registry (Augsburg, Germany), we estimated age-adjusted IR in people with and without diabetes, corresponding relative risks (RR), and time trends from 1985 to 2016 using Poisson regression., Results: There were 19,683 people with first MI (34% fatal MI, 71% men, 30% with diabetes) between 1985 and 2016. In the entire study population, the IR of first MI decreased from 359 (95% CI: 345-374) to 236 (226-245) per 100,000 person years. In men with diabetes, IR decreased only in 2013-2016. This was due to first non-fatal MI, where IR in men with diabetes increased until 2009-2012, and slightly decreased in 2013-2016. Overall, fatal MI declined stronger than first non-fatal MI corresponding to IRs. The RR of first MI substantially increased among men from 1.40 (1.22-1.61) in 1985-1988 to 2.60 (2.26-2.99) in 1997-2000 and moderately decreased in 2013-2016: RR: 1.75 (1.47-2.09). Among women no consistent time trend for RR was observed. Time trends for RR were similar regarding first non-fatal MI and fatal MI., Conclusions: Over the study period, we found a decreased incidence of first MI and fatal MI in the entire study population. The initial increase of first non-fatal MI in men with diabetes needs further research. The gap between populations with and without diabetes remained., (© 2024. The Author(s).)

Background: The risk of cardiovascular disease (CVD) mortality in individuals with an alerting reaction, assessed by hypertension in the first blood pressure (BP) reading but normal BP in further readings, remains unknown in the general population., Methods and Results: In a sample of 11 146 adults (51.5% men and 48.5% women) with a mean age of 47.1 years (SD ± 12.3) from a German population-based cohort, we analyzed risk factors and CVD mortality risk associated with an alerting reaction. An alerting reaction was prevalent in 10.2% of the population and associated with sociodemographic, lifestyle, and somatic CVD risk factors. Within a mean follow-up period of 22.7 years (SD ± 7.05 years; max: 32 years; 253 201 person years), 1420 (12.7%) CVD mortality cases were observed. The CVD mortality rate associated with an alerting reaction was significantly higher than in normotension (64 vs. 32 cases/10 000 person-years), but lower than hypertension (118 cases/10 000 person-years). Correspondingly, the alerting reaction was associated with a 23% higher hazard ratio of CVD mortality than normal blood pressure [hazard ratio 1.23 (95% confidence interval 1.02-1.49), P  = 0.04]. However, adjustment for antihypertensive medication use attenuated this association [1.19 (0.99-1.44), P  = 0.06]., Conclusion: The results may warrant monitoring of an alerting reaction as a preventive measure of CVD mortality in untreated individuals with elevated first BP readings, as well as optimized treatment in treated individuals., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Aims: Myocardial infarction (MI) is a major cause of death and disability worldwide. Most metabolomics studies investigating metabolites predicting MI are limited by the participant number and/or the demographic diversity. We sought to identify biomarkers of incident MI in the COnsortium of METabolomics Studies., Methods and Results: We included 7897 individuals aged on average 66 years from six intercontinental cohorts with blood metabolomic profiling (n = 1428 metabolites, of which 168 were present in at least three cohorts with over 80% prevalence) and MI information (1373 cases). We performed a two-stage individual patient data meta-analysis. We first assessed the associations between circulating metabolites and incident MI for each cohort adjusting for traditional risk factors and then performed a fixed effect inverse variance meta-analysis to pull the results together. Finally, we conducted a pathway enrichment analysis to identify potential pathways linked to MI. On meta-analysis, 56 metabolites including 21 lipids and 17 amino acids were associated with incident MI after adjusting for multiple testing (false discovery rate < 0.05), and 10 were novel. The largest increased risk was observed for the carbohydrate mannitol/sorbitol {hazard ratio [HR] [95% confidence interval (CI)] = 1.40 [1.26-1.56], P < 0.001}, whereas the largest decrease in risk was found for glutamine [HR (95% CI) = 0.74 (0.67-0.82), P < 0.001]. Moreover, the identified metabolites were significantly enriched (corrected P < 0.05) in pathways previously linked with cardiovascular diseases, including aminoacyl-tRNA biosynthesis., Conclusions: In the most comprehensive metabolomic study of incident MI to date, 10 novel metabolites were associated with MI. Metabolite profiles might help to identify high-risk individuals before disease onset. Further research is needed to fully understand the mechanisms of action and elaborate pathway findings., Competing Interests: Conflict of interest: R.A.M. is a consultant for Pharmavite for work unrelated to this study. All other authors declare no competing financial interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Metadata from epidemiological studies, including chronic disease outcome metadata (CDOM), are important to be findable to allow interpretability and reusability. We propose a comprehensive metadata schema and used it to assess public availability and findability of CDOM from German population-based observational studies participating in the consortium National Research Data Infrastructure for Personal Health Data (NFDI4Health). Additionally, principal investigators from the included studies completed a checklist evaluating consistency with FAIR principles (Findability, Accessibility, Interoperability, Reusability) within their studies. Overall, six of sixteen studies had complete publicly available CDOM. The most frequent CDOM source was scientific publications and the most frequently missing metadata were availability of codes of the International Classification of Diseases, Tenth Revision (ICD-10). Principal investigators' main perceived barriers for consistency with FAIR principles were limited human and financial resources. Our results reveal that CDOM from German population-based studies have incomplete availability and limited findability. There is a need to make CDOM publicly available in searchable platforms or metadata catalogues to improve their FAIRness, which requires human and financial resources., (© 2023. The Author(s).)

Objective: The presence and intensity of symptoms vary in patients with unilateral vestibular hypofunction. We aimed to determine which saccadic and vestibulo-ocular reflex parameters best predict the presence of symptoms in unilateral vestibular hypofunction in order to better understand vestibular compensation and its implications for rehabilitation therapy., Methods: Video head impulse test data were analyzed from a subpopulation of 23 symptomatic and 10 currently symptom-free participants with unilateral vestibular hypofunction, embedded in the KORA (Cooperative Health Research in the Region of Augsburg) FF4 study, the second follow-up of the KORA S4 population-based health survey (2,279 participants)., Results: A higher number of catch-up saccades, a higher percentage of covert saccades, and a larger retinal error at 200 ms after the onset of the head impulse were associated with relevant symptoms in participants with unilateral vestibular hypofunction ( p  = 0.028, p  = 0.046, and p  = 0.038, respectively). After stepwise selection, the number of catch-up saccades and retinal error at 200 ms remained in the final logistic regression model, which was significantly better than a null model ( p  = 0.014). Age, gender, saccade amplitude, saccade latency, and VOR gain were not predictive of the presence of symptoms., Conclusion: The accuracy of saccadic compensation seems to be crucial for the presence of symptoms in unilateral vestibular hypofunction, highlighting the role of specific gaze stabilization exercises in rehabilitation. Early saccades, mainly triggered by the vestibular system, do not seem to compensate accurately enough, resulting in a relevant retinal error and the need for more as well as more accurate catch-up saccades, probably triggered by the visual system., Competing Interests: ES is the general manager and a shareholder of EyeSeeTec GmbH. NL is a shareholder and paid consultant of EyeSeeTec GmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Aubele, Grill, Eggert, Schneider, Strobl, Jahn, Müller, Holle, Linkohr, Heier, Ladwig and Lehnen.)

The coexistence of several chronic diseases is very common in older adults, making it crucial to understand multimorbidity (MM) patterns and associated mortality. We aimed to determine the prevalence of MM and common chronic disease combinations, as well as their impact on mortality in men and women aged 65 years and older using the population-based KORA-Age study, based in South of Germany. The chronic disease status of the participants was determined in 2008/9, and mortality status was followed up until 2016. MM was defined as having at least two chronic diseases. We used Cox proportional hazard models to calculate the hazard ratios (HRs) and the 95% confidence intervals (CIs) for associations between MM and all-cause mortality. During the study period 495 men (24.6%) and 368 women (17.4%) died. Although the MM prevalence was almost the same in men (57.7%) and women (60.0%), the overall effect of MM on mortality was higher in men (HR: 1.81, 95% CI: 1.47-2.24) than in women (HR: 1.28, 95% CI: 1.01-1.64; p -value for interaction <0.001). The type of disease included in the MM patterns had a significant impact on mortality risk. For example, when both heart disease and diabetes were included in the combinations of two and three diseases, the mortality risk was highest. The risk of premature death does not only depend on the number of diseases but also on the specific disease combinations. In this study, life expectancy depended strongly on a few diseases, such as diabetes, hypertension, and heart disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Arshadipour, Thorand, Linkohr, Ladwig, Heier and Peters.)

Results from a population-based study suggest sex-specific patterns of self-reported child maltreatment, more frequently reported in former West than East Germany. Aim of the current study was to examine these patterns in two regional samples of the former East- (SHIP, 2008 - 2012) and West German (KORA, 2013 - 2014) population. Child maltreatment was assessed using the Childhood Trauma Screener (CTS). Overall, child maltreatment was less often reported in the East German sample, compared to the West German sample. The most prominent differences were identified in self-rated emotional violence (east 6.1%, west 8.7%), physical violence (east 5.7%, west 10.3%) and physical neglect (east 10.0%, west 19.2%). However, we could not find differences in sex-specific patterns between the East and West German samples. Results were discussed within a historical context, since the events took place before the German reunification in two oppose political systems., Competing Interests: HJG hat Reisekostenunterstützungen und Referentenhonorare von folgenden Firmen erhalten: Fresenius Medical Care, Neuraxpharm, Servier und Janssen Cilag sowie Forschungsunterstützung von Fresenius Medical Care., (Thieme. All rights reserved.)

Introduction: Lead exposure remains of continuing concern due to its known and suspected impacts on human health and has been designated as a priority substance for investigation in human biomonitoring studies by the EU. The aims of this study were to measure blood lead levels (BLL) in a population based cohort of middle-aged individuals without major current exposures to lead, and to compare these to historical blood lead levels obtained thirty years earlier., Methods: The population-based KORA study from 1984 to 2001 included inhabitants of the Augsburg Region, Germany. During 2018 to 2019, a subsample of these participants (KORA-Fit) was invited for interview regarding demographic and lifestyle factors, physical examination and blood withdrawal. Blood samples were stored at -80C prior to measurement of BLL via graphite furnace atomic absorption spectroscopy (GF-AAS). Descriptive and multivariable analyses were performed., Results: BLLs were measured in 3033 eligible persons aged 54 to 73, establishing a geometric mean (GM) BLL of 24.8 μg/l in 2018/19. Of these, 555 (18%) had BLL above proposed 95th percentile reference values of the German Environment Agency. Only small differences were found in BLL stratified by sociodemographic categories, however regular smokers had higher GM BLL (26.1 μg/l) compared to never smokers (23.7 μg/l), and an increasing BLL with increased wine consumption was noted. For 556 individuals, BLLs (GM: 54.0 μg/l) reduced by 35% in men and 50% in women compared to levels in 1987/88 with only 1.4% of individuals having an unchanged or increased BLL., Discussion: KORA-Fit provided contemporary normative data for BLL in a Western European population without major current sources of lead exposure. Mean BLLs have fallen since the 1980s using historical BLL data which is likely linked to the ban of leaded gasoline. Nevertheless, BLLs in this population remain elevated at levels associated with morbidity and mortality., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Management of radiological incidental findings (IF) is of rising importance; however, psychosocial implications of IF reporting remain unclear. We compared long-term psychosocial effects between individuals who underwent whole-body magnetic resonance imaging (MRI) with and without reported IF, and individuals who did not undergo imaging. We used a longitudinal population-based cohort from Western Europe. Longitudinal analysis included three examinations (exam 1, 6 years prior to MRI; exam 2, MRI; exam 3, 4 years after MRI). Psychosocial outcomes included PHQ-9 (Patient Health Questionnaire), DEEX (Depression and Exhaustion Scale), PSS-10 (Perceived Stress Scale) and a Somatization Scale. Univariate analyses and adjusted linear mixed models were calculated. Among 855 included individuals, 25% (n = 212) underwent MRI and 6% (n = 50) had at least one reported IF. Compared to MRI participants, non-participants had a higher psychosocial burden indicated by PHQ-9 in exam 1 (3.3 ± 3.3 vs. 2.5 ± 2.3) and DEEX (8.6 ± 4.7 vs. 7.7 ± 4.4), Somatization Scale (5.9 ± 4.3 vs. 4.8 ± 3.8) and PSS-10 (14.7 ± 5.7 vs. 13.7 ± 5.3, all p < 0.05) in exam 3. MRI participation without IF reporting was significantly associated with lower values of DEEX, PHQ-9 and Somatization Scale. There were no significant differences at the three timepoints between MRI participants with and without IF. In conclusion, individuals who voluntarily participated in whole-body MRI had less psychosocial burden and imaging and IF reporting were not associated with adverse long-term psychosocial consequences. However, due to the study design we cannot conclude that the MRI exam itself represented a beneficial intervention causing improvement in mental health scores.

Aims/hypothesis: The prevalence of type 2 diabetes is increasing worldwide, and previous studies have suggested that it is higher in individuals who are seropositive for herpesviruses. This study examines the prospective association of herpesviruses with (pre)diabetes to evaluate their potential role in diabetes aetiology., Methods: Two follow-up examinations of the German population-based KORA cohort (F4 and FF4) were used to identify participants with normal glucose tolerance at baseline, thus being at risk for (pre)diabetes (n = 1257). All participants had repeated OGTTs and antibody measurements for herpes simplex virus (HSV) 1 and 2, varicella-zoster virus, Epstein-Barr virus, cytomegalovirus (CMV) and human herpesvirus 6 and 7. Regression models were used to evaluate the association between serostatus with (pre)diabetes incidence after a 7 year follow-up and HbA 1c ., Results: HSV2 and CMV were associated with (pre)diabetes incidence after adjustment for sex, age, BMI, education, smoking, physical activity, parental diabetes, hypertension, lipid levels, insulin resistance and fasting glucose. Seropositivity of both viruses was also cross-sectionally associated with higher HbA 1c at baseline, with the association of HSV2 being independent of confounders, including the prevalence of (pre)diabetes itself. While seropositivity for multiple herpesviruses was associated with a higher incidence of (pre)diabetes, this association was not independent of confounders., Conclusions/interpretation: The associations of HSV2 and CMV serostatus with (pre)diabetes incidence indicate that these herpesviruses may contribute to the development of impaired glucose metabolism. Our results highlight the link between viral infection and (pre)diabetes, and the need for more research evaluating viral prevention strategies., (© 2022. The Author(s).)

The Framingham Risk Score to predict 30-year risk (FRS30y) of cardiovascular disease (CVD) constitutes an important tool for long-term risk prediction. However, due to its complex statistical properties and the paucity of large population-based cohorts with appropriate data, validation of the FRS30y is lacking. A population-based cohort from Southern Germany (N = 3110, 1516 (48.7%) women) was followed up for a median time of 29.5 [18.7, 31.2] years. Discrimination and calibration were assessed for the original, recalibrated and refitted FRS30y version. During follow up, 620 incident CVD events (214 in women) occurred. The FRS30y showed adequate discrimination (original and recalibrated version: Area under the curve (AUC): 78.4 for women and 74.9 for men) but overestimated actual CVD risk (original version: discordance 45.4% for women and 37.3% for men, recalibrated version: 37.6% and 28.6%, respectively). Refitting showed substantial improvement in neither discrimination nor calibration. The performance of FRS30y is adequate for long-term CVD risk prediction and could serve as an important tool in risk communication, especially for younger audiences.

Chronic low-grade inflammation has been proposed as a linking mechanism between obesity and the development of inflammation-related conditions such as insulin resistance and cardiovascular disease. Despite major advances in the last 2 decades, the complex relationship between inflammation and obesity remains poorly understood. Therefore, we aimed to identify novel inflammation-related proteins associated with adiposity. We investigated the association between BMI and waist circumference and 72 circulating inflammation-related proteins, measured using the Proximity Extension Assay (Olink Proteomics), in 3,308 participants of four independent European population-based studies (KORA-Fit, BVSII, ESTHER, and Bialystok PLUS). In addition, we used body fat mass measurements obtained by Dual-energy X-ray absorptiometry (DXA) in the Bialystok PLUS study to further validate our results and to explore the relationship between inflammation-related proteins and body fat distribution. We found 14 proteins associated with at least one measure of adiposity across all four studies, including four proteins for which the association is novel: DNER, SLAMF1, RANKL, and CSF-1. We confirmed previously reported associations with CCL19, CCL28, FGF-21, HGF, IL-10RB, IL-18, IL-18R1, IL-6, SCF, and VEGF-A. The majority of the identified inflammation-related proteins were associated with visceral fat as well as with the accumulation of adipose tissue in the abdomen and the trunk. In conclusion, our study provides new insights into the immune dysregulation observed in obesity that might help uncover pathophysiological mechanisms of disease development., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: While risk factors for age-related diseases may increase multimorbidity (MM), early life deprivation may also accelerate the development of chronic diseases and MM., Methods: This study explores the prevalence and pattern of MM in 65-71 year-old individuals born before, during, and after World War II in Southern Germany based on two large cross-sectional KORA (Cooperative Health Research in the Region of Augsburg) -Age studies in 2008/9 and 2016. MM was defined as having at least two chronic diseases, and birth periods were classified into five phases: pre-war, early war, late war, famine, and after the famine period. Logistic regression models were used to analyze the effect of the birth phases on MM with adjustment for sociodemographic and lifestyle risk factors. Furthermore, we used agglomerative hierarchical clustering to investigate the co-occurrence of diseases., Results: Participants born during the late war phase had the highest prevalence of MM (62.2%) and single chronic diseases compared to participants born during the other phases. Being born in the late war phase was significantly associated with a higher odds of MM (OR = 1.83, 95% CI: 1.15-2.91) after adjustment for sociodemographic and lifestyle factors. In women, the prevalence of joint, gastrointestinal, eye diseases, and anxiety was higher, while heart disease, stroke, and diabetes were more common in men. Moreover, three main chronic disease clusters responsible for the observed associations were identified as: joint and psychosomatic, cardiometabolic and, other internal organ diseases., Conclusions: Our findings imply that adverse early-life exposure may increase the risk of MM in adults aged 65-71 years. Moreover, identified disease clusters are not coincidental and require more investigation., (© 2022. The Author(s).)

Objective: To estimate age-related macular degeneration (AMD) incidence/progression across a wide age range., Methods and Analysis: AMD at baseline and follow-up (colour fundus imaging, Three Continent AMD Consortium Severity Scale, 3CACSS, clinical classification, CC) was assessed for 1513 individuals aged 35-95 years at baseline from three jointly designed population-based cohorts in Germany: Kooperative Gesundheitsforschung in der Region Augsburg (KORA-Fit, KORA-FF4) and Altersbezogene Untersuchungen zur Gesundheit der Universität Regensburg (AugUR) with 18-year, 14-year or 3-year follow-up, respectively. Baseline assessment included lifestyle, metabolic and genetic markers. We derived cumulative estimates, rates and risk factor association for: (1) incident early AMD, (2) incident late AMD among no AMD at baseline (definition 1), (3) incident late AMD among no/early AMD at baseline (definition 2), (4) progression from early to late AMD., Results: Incidence/progression increased by age, except progression in 70+-year old. We observed 35-55-year-old with 3CACSS-based early AMD who progressed to late AMD. Predominant risk factor for incident late AMD definition 2 was early AMD followed by genetics and smoking. When separating incident late AMD definition 1 from progression (instead of combined as incident late AMD definition 2), estimates help judge an individual's risk based on age and (3CACSS) early AMD status: for example, for a 65-year old, 3-year late AMD risk with no or early AMD is 0.5% or 7%, 3-year early AMD risk is 3%; for an 85-year old, these numbers are 0.5%, 21%, 12%, respectively. For CC-based 'early/intermediate' AMD, incidence was higher, but progression was lower., Conclusion: We provide a practical guide for AMD risk for ophthalmology practice and healthcare management and document a late AMD risk for individuals aged <55 years., Competing Interests: Competing interests: TB is a member of the advisory board of Novartis; this is unrelated to the work presented here. RPF is a consultant for Novartis, Bayer, Roche/Genentech, Allergan, Alimera, Böhringer-Ingelheim, Chiesi, ProQR, Opthea and Inositec, and receives research support from Novartis, Biogen, Zeiss Meditec, Heidelberg Engineering and Centrevue; none of this has any relation to the presented work. HH received honoraria for lectures and advisory boards unrelated to this work from Alcon, Allergan, Apellis, Bayer, Novartis and Theapharm. BHFW has cooperation agreements for projects unrelated to this work with Alcon, Allergan, Apellis, Gensight Biologics, Novartis, Shire, F. Hoffmann-La Roche and ModernaTX, and is a member of the clinical advisory board of Gyroscope Therapeutics. IMH has received support from Roche Diagnostics for a project related to age-related macular degeneration, but unrelated to this work presented here. No conflicting relationship exists for the other authors., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The Patient Health Questionnaire-9 (PHQ-9) has been proposed as a reliable and valid screening instrument for depressive symptoms with one latent factor. However, studies explicitly testing alternative model structures found support for a two-dimensional structure reflecting a somatic and a cognitive-affective dimension. We investigated the bidimensional structure of the PHQ-9, with a somatic (sleeping problems, fatigability, appetitive problems, and psychomotor retardation) and a cognitive-affective dimension (lack of interest, depressed mood, negative feelings about self, concentration problems, and suicidal ideation), and tested for sex- and regional-differences., Methods: We have included data from the GEnder-Sensitive Analyses of mental health trajectories and implications for prevention: A multi-cohort consortium (GESA). Privacy-preserving analyses to provide information on the overall population and cohort-specific information and analyses of variance to compare depressive, somatic and cognitive-affective symptoms between sexes and cohorts were executed in DataSHIELD. In order to determine the dimensionality and measurement invariance of the PHQ-9 we tested three models (1 factor, 2 correlated factors, and bifactor) via confirmatory analyses and performed multi-group confirmatory factor analysis., Results: Differences between sex and cohorts exist for PHQ-9 and for both of its dimensions. Women reported depressive symptoms in general as well as somatic and cognitive-affective symptoms more frequently. For all tested models an acceptable to excellent fit was found, consistently indicating a better model fit for the two-factor and bifactor model. Scalar measurement invariance was established between women and men, the three cohorts, and their interaction., Conclusions: The two facets of depression should be taken into account when using PHQ-9, while data also render support to a general factor. Somatic and cognitive-affective symptoms assessed by the PHQ-9 can be considered equivalent across women and men and between different German populations from different regions.

Objectives: We explored the male-female health-survival paradox in the context of health expectancy (HE) at age 65 and thereafter, using three different morbidity measures and different severity cut-offs with and without adjustments for the share of nursing home residents., Methods: HE at ages 65, 70, 75, 80, and 85 was estimated with the Sullivan method, linking morbidity prevalence from the KORA (Cooperative Health Research in the Region of Augsburg)-Age study to 2016 Bavarian mortality data. Morbidity measures comprised deficit accumulation (Frailty Index, FI, cut-offs 0.08 and 0.25), disability (Health Assessment Questionnaire-Disability Index, HAQ-DI, cut-off >0) and participation (Global Activity Limitation Indicator, GALI, "limited" vs "not limited")., Results: Morbidity data were available for 4083 participants (52.7% female). HE was lower in women than in men at all ages. Differences in morbidity prevalence, absolute HE, and health proportions of life expectancy (relative HE) increased with age for FI ≥ 0.25 and GALI, but not for HAQ-DI > 0 and FI > 0.08. Accounting for the share of nursing home residents resulted in a slight reduction of HE estimates but had no impact on estimated sex differences., Conclusions: In HE at age 65 and thereafter, women's health disadvantage was larger than their life expectancy advantage over men., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: Management of incidental findings (IF) remains controversial but highly relevant. Our aim was to assess the frequency, management and psychosocial consequences of IF reporting in a population-based cohort study undergoing whole-body MR imaging., Methods: The study was nested in a prospective cohort from a longitudinal, population-based cohort (KORA-FF4) in southern Germany. All MR obtained on 3 T MR scanner were reviewed by board-certified radiologists regarding clinically relevant IF. A baseline and follow-up questionnaires including PHQ-9 were completed prior to and 6-month after to the scan., Results: Of 400 participants (56.3 ± 9.2years, 58 % male) undergoing whole-body MR, IF were found in 22 % of participants (n = 89); most frequently located in the abdominal sequences. In the pre-scan survey, most participants stated as the motivation that they wanted to "contribute to a scientific purpose" (91 %), while "knowing whether I'm healthy" was the most frequent motivation reported 6 months post-scan (88 %). The desire for IF reporting increased over time (pre- vs. 6-months-post-scan), also for clinically less important IF (72 % vs. 84 %, p = 0.001). Regarding psychosocial impact, a small portion (3.4 %) reported that awaiting the IF report added "definitely" or "very probably" additional stress burden. Of participants with reported IF, 56.8 % classified the results as "very helpful". In the post-scan survey moderate depression was observed in 3.3 % and severe depression in 1.2 %. This did not differ between participants with and without reported IF., Conclusion: In a cohort with whole-body MR imaging, the prevalence of IF was high. Participants considered reporting of IF highly important and added only minor psychological burden., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aims: The aim of the current study was to investigate the association of type 2 diabetes (T2D) and insulin treatment with changes in muscle mass, muscle strength, and physical performance in older adults., Methods: In 731 participants of the population-based KORA-Age study aged 74.6 ± 6.2 years (T2D: n = 118; insulin treatment: n = 20), skeletal muscle index (SMI [kg/m 2 ]), hand grip strength (GS [kg]), and a timed up and go test (TUG [s]) were performed at baseline and after a follow-up time of 3 years. The association of T2D and insulin therapy with changes in muscle parameters was analyzed using linear regression models., Results: After adjustment for sex, age, BMI, physical activity, smoking, and multimorbidity, T2D was associated with the change in SMI during follow-up (β - 0.1 (95% CI - 0.3 to - 0.02) kg/m 2 ; p = 0.02), but not with a change in GS (β - 0.9 (95% CI - 1.9 to 0.04) kg) or TUG (β - 0.1 (95% CI - 0.7 to 0.5) s). Insulin therapy was positively associated with change in SMI (β 0.6 (95% CI 0.3-0.9) kg/m 2 ; p = 0.001), but not in GS (β - 1.6 (95% CI - 4.1 to 0.8) kg) or TUG (β 1.6 (95% CI - 0.2-3.4) s) in comparison with treatment with oral anti-diabetic medication alone., Conclusions: Participants with T2D showed an accelerated decline in muscle mass compared to non-diabetic participants. Insulin therapy was associated with preserved muscle mass, but not muscle function parameters, indicating a discrepancy between muscle mass and function in this high-risk population.

Lifestyle, obesity, and the gut microbiome are important risk factors for metabolic disorders. We demonstrate in 1,976 subjects of a German population cohort (KORA) that specific microbiota members show 24-h oscillations in their relative abundance and identified 13 taxa with disrupted rhythmicity in type 2 diabetes (T2D). Cross-validated prediction models based on this signature similarly classified T2D. In an independent cohort (FoCus), disruption of microbial oscillation and the model for T2D classification was confirmed in 1,363 subjects. This arrhythmic risk signature was able to predict T2D in 699 KORA subjects 5 years after initial sampling, being most effective in combination with BMI. Shotgun metagenomic analysis functionally linked 26 metabolic pathways to the diurnal oscillation of gut bacteria. Thus, a cohort-specific risk pattern of arrhythmic taxa enables classification and prediction of T2D, suggesting a functional link between circadian rhythms and the microbiome in metabolic diseases., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Retirement is a major life event potentially associated with changes in relevant risk factors for cardiovascular and metabolic conditions. This study analyzes the effect of retirement on behavioral and biomedical risk factors for chronic disease, together with subjective health parameters using Southern German epidemiological data. We used panel data from the KORA cohort study, consisting of 11,168 observations for individuals 45-80 years old. Outcomes included health behavior (alcohol, smoking, physical activity), biomedical risk factors (body-mass-index (BMI), waist-to-hip ratio (WHR), glycosylated hemoglobin (HbA1c), total cholesterol/HDL quotient, systolic/diastolic blood pressure), and subjective health (SF12 mental and physical scales, self-rated health). We applied a parametric regression discontinuity design based on age thresholds for pension eligibility. Robust results after p-value corrections for multiple testing showed an increase in BMI in early retirees (at the age of 60) [β = 1.11, corrected p-val. < 0.05] and an increase in CHO/HDL in regular retirees (age 65) [β = 0.47, corrected p-val. < 0.05]. Stratified analyses indicate that the increase in BMI might be driven by women and low educated individuals retiring early, despite increasing physical activity. The increase in CHO/HDL might be driven by men retiring regularly, alongside an increase in subjective physical health. Blood pressure also increased, but the effect differs by retirement timing and sex and is not always robust to sensitivity analysis checks. Our study indicates that retirement has an impact on different risk factors for chronic disease, depending on timing, sex and education. Regular male, early female, and low educated retirees should be further investigated as potential high-risk groups for worsening risk factors after retirement. Future research should investigate if and how these results are linked: in fact, especially in the last two groups, the increase in leisure time physical activity might not be enough to compensate for the loss of work-related physical activity, leading thus to an increase in BMI., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)