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ZusammenfassungErste Ergebnisse einer bundesweiten Studie deuten auf geschlechtsspezifische Muster mit weniger berichteten Fällen von Kindesvernachlässigung und Gewalt in den Neuen im Vergleich zu den Alten Bundesländern. Ziel der vorliegenden Studie war es diese Ergebnisse in zwei größeren regionalen Stichproben zu überprüfen. Methode: Prävalenzen von Vernachlässigung- und Gewalterfahrung in der Kindheit wurden mithilfe des Childhood Trauma Screeners in den Regionen Greifswald (SHIP, 2008–2012) und Augsburg (KORA, 2013–2014) erhoben. Analyse geschlechtsstratifizierter und regionaler Unterschiede. Die Prävalenzen beider lokalen Stichproben wurden anschließend miteinander verglichen. Ergebnisse: Insgesamt wurden Vernachlässigung und Gewalt in der Kindheit seltener in der Nord-Ostdeutschen Stichprobe (SHIP) berichtet. Die deutlichsten Unterschiede fanden sich in den Kategorien emotionale Gewalt (SHIP: 6,1%, KORA: 8,7%), körperliche Gewalt (SHIP: 5,7%, KORA: 10,3%) sowie körperliche Vernachlässigung (SHIP:10,0%, KORA: 19,2%). Geschlechtsspezifische Muster von Vernachlässigungs- und Gewalterfahrung in der Kindheit unterschieden sich in SHIP und KORA nicht. Schlussfolgerung: Wir diskutieren den möglichen Einfluss des sozio-politischen Kontexts auf die Prävalenz von Vernachlässigung und Gewalt in der Kindheit, da alle selbstberichteten Ereignisse in die Zeit vor der Wiedervereinigung in zwei politisch unterschiedliche Systeme fallen.

Supplemental Table 1: Comparison of epidemiological risk factors in Barrett patients (n= 587) and population controls (n= 587) matched by gender and age

Endoscopic screening for Barrett's esophagus as the major precursor lesion for esophageal adenocarcinoma is mostly offered to patients with symptoms of gastroesophageal reflux disease (GERD). However, other epidemiologic risk factors might affect the development of Barrett's esophagus and esophageal adenocarcinoma. Therefore, efforts to improve the efficiency of screening to find the Barrett's esophagus population “at risk” compared with the normal population are needed. In a cross-sectional analysis, we compared 587 patients with Barrett's esophagus from the multicenter German BarrettNET registry to 1976 healthy subjects from the population-based German KORA cohort, with and without GERD symptoms. Data on demographic and lifestyle factors, including age, gender, smoking, alcohol consumption, body mass index, physical activity, and symptoms were collected in a standardized epidemiologic survey. Increased age, male gender, smoking, heavy alcohol consumption, low physical activity, low health status, and GERD symptoms were significantly associated with Barrett's esophagus. Surprisingly, among patients stratified for GERD symptoms, these associations did not change. Demographic, lifestyle, and clinical factors as well as GERD symptoms were associated with Barrett's esophagus development in Germany, suggesting that a combination of risk factors could be useful in developing individualized screening efforts for patients with Barrett's esophagus and GERD in Germany.

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 HbA1c. 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 HbA1c 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. Graphical abstract

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.Erste Ergebnisse einer bundesweiten Studie deuten auf geschlechtsspezifische Muster mit weniger berichteten Fällen von Kindesvernachlässigung und Gewalt in den Neuen im Vergleich zu den Alten Bundesländern. Ziel der vorliegenden Studie war es diese Ergebnisse in zwei größeren regionalen Stichproben zu überprüfen. Methode: Prävalenzen von Vernachlässigung- und Gewalterfahrung in der Kindheit wurden mithilfe des Childhood Trauma Screeners in den Regionen Greifswald (SHIP, 2008–2012) und Augsburg (KORA, 2013–2014) erhoben. Analyse geschlechtsstratifizierter und regionaler Unterschiede. Die Prävalenzen beider lokalen Stichproben wurden anschließend miteinander verglichen. Ergebnisse: Insgesamt wurden Vernachlässigung und Gewalt in der Kindheit seltener in der Nord-Ostdeutschen Stichprobe (SHIP) berichtet. Die deutlichsten Unterschiede fanden sich in den Kategorien emotionale Gewalt (SHIP: 6,1%, KORA: 8,7%), körperliche Gewalt (SHIP: 5,7%, KORA: 10,3%) sowie körperliche Vernachlässigung (SHIP:10,0%, KORA: 19,2%). Geschlechtsspezifische Muster von Vernachlässigungs- und Gewalterfahrung in der Kindheit unterschieden sich in SHIP und KORA nicht. Schlussfolgerung: Wir diskutieren den möglichen Einfluss des sozio-politischen Kontexts auf die Prävalenz von Vernachlässigung und Gewalt in der Kindheit, da alle selbstberichteten Ereignisse in die Zeit vor der Wiedervereinigung in zwei politisch unterschiedliche Systeme fallen.

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.

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.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 HbAHSV2 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 HbAThe 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.

BackgroundWhile risk factors for age-related diseases may increase multimorbidity (MM), early life deprivation may also accelerate the development of chronic diseases and MM.MethodsThis 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 KORA (Cooperative Health Research in the Region of Augsburg) -Age studies. 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.ResultsParticipants 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: joint and psychosomatic, cardiometabolic and, internal organs diseases.ConclusionsOur 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.

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 two decades, the complex interplay between immune regulators 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.

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.

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 ± 6.2years (T2D: n = 118; insulin treatment: n = 20), skeletal muscle index (SMI [kg/m2]), 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 3years. 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/m2; 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/m2; 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.

To establish the effect of different degrees and kinds of physical activity on bone marrow fat (BMAT) content at different anatomical locations in a population-based cohort study undergoing whole-body MR imaging.Subjects of the KORA FF4 study without known cardiovascular disease underwent BMAT fat fraction (FF) quantification in L1 and L2 vertebrae and femoral heads/necks (hip) via a 2-point T1-weighted VIBE Dixon sequence. BMAT-FF was calculated as mean value (fat image) divided by mean value (fat + water image). Physical activity was determined by self-assessment questionnaire regarding time spent exercising, non-exercise walking, non-exercise cycling, and job-related physical activity.A total of 385 subjects (96% of 400 available; 56 ± 9.1 years; 58% male) were included in the analysis. Exercise was distributed quite evenly (29% 2 h/week; 31% ~ 1 h/week (regularly); 15% ~ 1 h/week (irregularly); 26% no physical activity). BMAT-FF was 52.6 ± 10.2% in L1, 56.2 ± 10.3% in L2, 87.4 ± 5.9% in the right hip, and 87.2 ± 5.9% in the left hip (all p 0.001). Correlation of BMAT-FF between spine and hip was only moderate (r 0.42 to 0.46). Spinal BMAT-FF, but not hip BMAT-FF, was inversely associated with exercise 2 h/week (p ≤ 0.02 vs. p ≥ 0.35, respectively). These associations remained significant after adjusting for age, gender, waist circumference, and glucose tolerance. No coherent association was found between BMAT-FF and physical activity in the less active groups.In our study, exercise was inversely correlated with vertebral BMAT-FF, but not hip BMAT-FF, when exercising for more than 2 h per week. Physical activity seems to affect the spine at least preferentially compared to the hip.• In our population-based cohort, at least 2 h of physical activity per week were required to show lower levels of bone marrow adipose tissue fat fraction in MRI. • Physical activity seems to affect bone marrow adipose tissue at least preferentially at the spine in contrast to the proximal femur.

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.

SummaryTo combat the epidemic increase in Type-2-Diabetes (T2D), risk factors need to be identified. Diet, lifestyle and the gut microbiome are among the most important factors affecting metabolic health. We demonstrate in 1,976 subjects of a prospective population cohort that specific gut microbiota members show diurnal oscillations in their relative abundance and we identified 13 taxa with disrupted rhythmicity in T2D. Prediction models based on this signature classified T2D with an area under the curve of 73%. BMI as microbiota-independent risk marker further improved diagnostic classification of T2D. The validity of this arrhythmic risk signature to predict T2D was confirmed in 699 KORA subjects five years after initial sampling. Shotgun metagenomic analysis linked 26 pathways associated with xenobiotic, amino acid, fatty acid, and taurine metabolism to the diurnal oscillation of gut bacteria. In summary, we determined a cohort-specific risk pattern of arrhythmic taxa which significantly contributes to the classification and prediction of T2D, highlighting the importance of circadian rhythmicity of the microbiome in targeting metabolic human diseases.

Introduction Detailed mechanisms in the pathophysiology of diabetes disease are poorly understood, but structural alterations in various organ systems incur an elevated risk for cardiovascular events and adverse outcome. The aim of this study was to compare multiorgan subclinical disease phenotypes by magnetic resonance (MR) imaging to study differences between subjects with prediabetes, diabetes, and normal controls. Materials and Methods Subjects without prior cardiovascular disease were enrolled in a prospective case-control study and underwent multiorgan MR for the assessment of metabolic and arteriosclerotic alterations, including age-related white matter changes, hepatic proton density fat fraction, visceral adipose tissue volume, left ventricular remodeling index, carotid plaque, and late gadolinium enhancement. Magnetic resonance features were summarized in a phenotypic-based score (range, 0-6). Univariate, multivariate correlation, and unsupervised clustering were performed. Results Among 243 subjects with complete multiorgan MR data sets included in the analysis (55.6 ± 8.9 years, 62% males), 48 were classified as subjects with prediabetes and 38 as subjects with diabetes. The MR phenotypic score was significantly higher in subjects with prediabetes and diabetes as compared with controls (mean score, 3.00 ± 1.04 and 2.69 ± 0.98 vs 1.22 ± 0.98, P < 0.001 respectively), also after adjustment for potential confounders. We identified 2 clusters of MR phenotype patterns associated with glycemic status (P < 0.001), independent of the MR score (cluster II-metabolic specific: odds ratio, 2.49; 95% CI, 1.00-6.17; P = 0.049). Discussion Subjects with prediabetes and diabetes have a significantly higher phenotypic-based score with a distinctive multiorgan phenotypic pattern, which may enable improved disease characterization.

Endoscopic screening for Barrett's esophagus as the major precursor lesion for esophageal adenocarcinoma is mostly offered to patients with symptoms of gastroesophageal reflux disease (GERD). However, other epidemiologic risk factors might affect the development of Barrett's esophagus and esophageal adenocarcinoma. Therefore, efforts to improve the efficiency of screening to find the Barrett's esophagus population “at risk” compared with the normal population are needed. In a cross-sectional analysis, we compared 587 patients with Barrett's esophagus from the multicenter German BarrettNET registry to 1976 healthy subjects from the population-based German KORA cohort, with and without GERD symptoms. Data on demographic and lifestyle factors, including age, gender, smoking, alcohol consumption, body mass index, physical activity, and symptoms were collected in a standardized epidemiologic survey. Increased age, male gender, smoking, heavy alcohol consumption, low physical activity, low health status, and GERD symptoms were significantly associated with Barrett's esophagus. Surprisingly, among patients stratified for GERD symptoms, these associations did not change. Demographic, lifestyle, and clinical factors as well as GERD symptoms were associated with Barrett's esophagus development in Germany, suggesting that a combination of risk factors could be useful in developing individualized screening efforts for patients with Barrett's esophagus and GERD in Germany.

Health projections often extrapolate from observations in current ageing cohorts, but health in older age may depend not only on individual characteristics but also on a person's historical context. Our objective was to investigate how health deficit accumulation trajectories after age 65 differed in five adjacent birth cohorts and according to individual life course characteristics. Data originate from the 2008/09 KORA (Cooperative Health Research in the Region of Augsburg)-Age cohort study from Southern Germany and their 2012 and 2016 follow-ups. Deficit accumulation was assessed using a Frailty Index. The effects of birth cohort membership and individual life course characteristics on deficit accumulation trajectories were analyzed using generalized linear mixed models. Out of 2701 participants (49% male) from five birth cohorts (1919-23, 1924-28, 1929-33, 1934-38, 1939-43), we included 2512 individuals with 5560 observations. Frailty Index levels were higher for women, smokers, alcohol abstainers, obese participants and persons with a sedentary lifestyle or living below the poverty threshold. We found higher age-specific Frailty Index levels for the two most recent birth cohorts (e.g. 61%, CI: [13%; 130%] for the 1934-38 as compared to the 1919-23 cohort), but the rate of deficit accumulation with age (7% per life year, (CI: [5%, 9%]) was cohort-independent. Results indicate that the historical context (birth cohort membership) may influence the number of accumulated health deficits after age 65 in addition to poverty and other individual life course characteristics, but BMI, physical activity and smoking remain the modifiable risk factors offering the highest prevention potential.

SUMMARYRisk stratification in patients with Barrett's esophagus (BE) to prevent the development of esophageal adenocarcinoma (EAC) is an unsolved task. The incidence of EAC and BE is increasing and patients are still at unknown risk. BarrettNET is an ongoing multicenter prospective cohort study initiated to identify and validate molecular and clinical biomarkers that allow a more personalized surveillance strategy for patients with BE. For BarrettNET participants are recruited in 20 study centers throughout Germany, to be followed for progression to dysplasia (low-grade dysplasia or high-grade dysplasia) or EAC for >10 years. The study instruments comprise self-administered epidemiological information (containing data on demographics, lifestyle factors, and health), as well as biological specimens, i.e., blood-based samples, esophageal tissue biopsies, and feces and saliva samples. In follow-up visits according to the individual surveillance plan of the participants, sample collection is repeated. The standardized collection and processing of the specimen guarantee the highest sample quality. Via a mobile accessible database, the documentation of inclusion, epidemiological data, and pathological disease status are recorded subsequently. Currently the BarrettNET registry includes 560 participants (23.1% women and 76.9% men, aged 22–92 years) with a median follow-up of 951 days. Both the design and the size of BarrettNET offer the advantage of answering research questions regarding potential causes of disease progression from BE to EAC. Here all the integrated methods and materials of BarrettNET are presented and reviewed to introduce this valuable German registry.

Aims This study examines exposure to anticholinergic and sedative (AS) medications in the general aging population using the Drug Burden Index (DBI) and to analyze the association of AS burden with vertigo, dizziness and balance problems (VDB, primary outcome) and falls (secondary outcome). Methods We performed a cross-sectional analysis of data from the second follow-up (FF4) in 2013/14 of the Cooperative Health Research in the Region of Augsburg (KORA)-S4 study. AS burden was classified as DBI > 0. Self-reported data of VDB and falls during the previous 12 months were collected. Multivariable logistic regression was used to estimate the association of AS burden with VDB and falls. Results 883 participants were included in this study (mean age 73.8 years, 48.4% female). AS burden was present in 167 (18.9%) participants, with the highest prevalence in those aged ≥80 years old (26.3%). In the adjusted analysis, AS burden was independently and significantly associated with VDB (Adjusted Odds Ratio (AOR): 1.73 [95% CI: 1.16, 2.56]). Conclusion This study provides reliable prevalence estimates of AS burden in older people using the DBI in Germany, also indicating a positive and significant association with VDB. As VDB are among the main reasons for falls, we do recommend including the AS burden calculation as routine risk assessment in ambulatory medical care.

Morbidity trends may result from cohort experiences in critical developmental age. Our objective was to compare the health status of 65–71 year-olds who were in critical developmental age before (1937–June 1945), during (June 1945–June 1948) and after (June 1948–1950) the early reconstruction and food crisis (ERFC) period in Germany following World War II. Data originate from the KORA (Cooperative Health Research in the Region of Augsburg)-Age study in Southern Germany. We used the 2008 baseline sample born 1937–1943 and the 2015 enrichment sample born 1944–1950. Health status was assessed as the number of accumulated health deficits using a Frailty Index (FI). Cohorts were defined based on co-occurrence of critical developmental age (gestation and the first 2 years of life) and the ERFC period. Cohort, age and sex effects on older-age health status were analyzed using generalized linear models. We included 590 (53% male) pre-war and war (PWW), 475 (51% male) ERFC and 171 post-currency reform (PCR) cohort participants (46% male). Adjusted for covariates, FI levels were significantly higher for the ERFC (Ratio 1.14, CL [1.06, 1.23]) but not for the PCR (Ratio 1.06, CL [0.94, 1.20]) as compared to the PWW cohort. Being in critical developmental age during the ERFC period increased FI levels in adults aged 65–71 years. Covariates did not explain these effects, suggesting a direct detrimental effect from being in critical developmental age during the ERFC period on older-age health. This expansion of morbidity in Germany was not detected in the PCR cohort.

Background: Psychosocial factors are supposed to play a central role in the development of allergic diseases. Associations with seasonal and perennial forms of allergies have not been investigated, yet. Objectives: The aim of the study was to investigate the associations of psychosocial factors (social status, depression, generalized anxiety, psychosocial stress, Type-D personality) with seasonal, perennial, and other forms of allergies in adults. Method: The analysis of self-reported data of the KORA FF4 study was performed with SAS 9.4. The sample consisted of 1,782 study participants in the study region of Augsburg (39–88 years, 61 years, 51.1% female). Descriptive bivariate statistics and multinomial logistic regression models were performed. Age, sex, family predisposition, and smoking status were considered possible confounders. Moreover, several sensitivity analyses were carried out to check whether missing values distorted the results. Results: A positive association between generalized anxiety and seasonal allergies was found in the multivariate model. Depression was positively, and anxiety negatively, associated with perennial allergies. No association between the analyzed psychosocial factors and other forms of allergies could be found. Conclusion: The results support the relevance of psychosocial factors in association with allergies. Looking at the psychosocial factors, a separate consideration of seasonal and perennial allergies seems reasonable. Further longitudinal studies should investigate the direction of the associations, the underlying mechanisms, and other psychosocial factors, such as coping mechanisms, in confirmed allergies.

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.

Introduction Aging is associated with increasing loss of physiological resilience and successive accumulation of physiological deficits. This can be measured through a frailty index which sums up symptoms, health conditions and impairments. One possible factor in preventing or delaying deficit accumulation is physical activity. The effect of leisure time physical activity on health is well investigated; however, the effect of household physical activity is less clear. The objective of this cross-sectional study was to examine the association of household physical activity with deficit accumulation while controlling for level of leisure time physical activity. Methods Data originates from the 2008 baseline assessment of the KORA (Cooperative Health Research in the Region of Augsburg)-Age study from Southern Germany. A frailty index of deficit accumulation (Deficit Accumulation Index, DAI) was constructed from 31 age-related health deficits. Physical activity was measured with the Physical Activity Scale for the Elderly (PASE). The association of deficit accumulation and physical activity was analyzed using negative binomial regression analysis. Results The participants' (n = 960, mean age 76 years, 49.0% female) DAI ranged from 0.00 to 0.68. Higher levels of both types of physical activity were statistically significantly associated with less deficit accumulation. Participants in the highest household (leisure time) physical activity quartile had 29% (30%) less deficits than participants in the respective lowest quartiles. Conclusion High levels of household physical activity might compensate for low levels of leisure time physical activity in the prevention of deficit accumulation. Further research efforts investigating the temporal sequence of this association are needed.

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 (BMI, waist-to-hip ratio (WHR), glycosylated hemoglobin (HbA1c), total cholesterol/HDL quotient, systolic/diastolic blood pressure), and subjective health (SF12 mental and physical, 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.

To determine the feasibility of a multi-step magnetic resonance imaging (MRI) approach for comprehensive assessment of hepatic steatosis defined as liver fat content of ≥5 % in an asymptomatic population. The study was approved by the institutional review board and written informed consent of all participants was obtained. Participants of a population-based study cohort underwent a three-step 3-T MRI-based assessment of liver fat. A dual-echo Dixon sequence was performed to identify subjects with hepatic steatosis, followed by a multi-echo Dixon sequence with proton density fat fraction estimation. Finally, single-voxel T2-corrected multi-echo spectroscopy was performed. A total of 215 participants completed the MRI protocol (56.3 % male, average age 57.2 ± 9.4 years). The prevalence of hepatic steatosis was 55 %. Mean liver proton density fat fraction was 9.2 ± 8.5 % by multi-echo Dixon and 9.3 ± 8.6 % by multi-echo spectroscopy (p = 0.51). Dual-echo Dixon overestimated liver fat fraction by 1.4 ± 2.0 % (p

Purpose: Age-related macular degeneration (AMD) is a common threat to vision. While classification of disease stages is critical to understanding disease risk and progression, several systems based on color fundus photographs are known. Most of these require in-depth and time-consuming analysis of fundus images. Herein, we present an automated computer-based classification algorithm.Design: Algorithm development for AMD classification based on a large collection of color fundus images. Validation is performed on a cross-sectional, population-based study.Participants: We included 120 656 manually graded color fundus images from 3654 Age-Related Eye Disease Study (AREDS) participants. AREDS participants were >55 years of age, and non-AMD sight-threatening diseases were excluded at recruitment. In addition, performance of our algorithm was evaluated in 5555 fundus images from the population-based Kooperative Gesundheitsforschung in der Region Augsburg (KORA; Cooperative Health Research in the Region of Augsburg) study.Methods: We defined 13 classes (9 AREDS steps, 3 late AMD stages, and 1 for ungradable images) and trained several convolution deep learning architectures. An ensemble of network architectures improved prediction accuracy. An independent dataset was used to evaluate the performance of our algorithm in a population-based study.Main Outcome Measures: kappa Statistics and accuracy to evaluate the concordance between predicted and expert human grader classification.Results: A network ensemble of 6 different neural net architectures predicted the 13 classes in the AREDS test set with a quadratic weighted kappa of 92% (95% confidence interval, 89%-92%) and an overall accuracy of 63.3%. In the independent KORA dataset, images wrongly classified as AMD were mainly the result of a macular reflex observed in young individuals. By restricting the KORA analysis to individuals >55 years of age and prior exclusion of other retinopathies, the weighted and unweighted kappa increased to 50% and 63%, respectively. Importantly, the algorithm detected 84.2% of all fundus images with definite signs of early or late AMD. Overall, 94.3% of healthy fundus images were classified correctly.Conclusions: Our deep learning algoritm revealed a weighted kappa outperforming human graders in the AREDS study and is suitable to classify AMD fundus images in other datasets using individuals >55 years of age.

Objective Encouraging physical activity is an important public health measure to reduce disability prevalence in the aged. The aims of this study were to determine the association between midlife physical activity and late-life disability and to investigate gender-specific differences. Method This data originates from the KORA-Age cohort, a follow-up in 2008 of the MONICA (Multinational Monitoring of Trends and Determinants in Cardiovascular Diseases)/KORA (Cooperative Health Research in the Region of Augsburg) S1–S4 surveys (1984–2001) situated in Augsburg, a city in Southern Germany. We applied a multivariable hurdle model to investigate the association of physical activity and disability. Results We analysed 3333 persons with a mean follow-up of 18 ± 5.5 years. Using hurdle models, moderate activity and high activity had a protective effect on the occurrence of disability (OR (odds ratio) = 0.80 and 0.73), but not on severity (i.e. number of limitations). We observed a strong gender-specific difference in this association, with men benefitting more from exercise. Conclusion Elevated physical activity reduces the risk of becoming disabled and postpones the onset of disability by several years, but we could not show an effect on the severity of disability. In addition, men seem to benefit more from leisure-time physical activity than women.

The impact of vertigo and dizziness on healthy ageing, and especially on participation, is not fully understood. The objective of this study was to investigate the association of vertigo and dizziness with self-perceived participation and autonomy in older non-institutionalised individuals, adjusted for the presence of other health conditions. Specifically, we wanted to investigate the different effects of vertigo and dizziness on specific components of participation, i.e. restrictions in indoor and outdoor autonomy, family role, social life and relationships, and work and education. Data originate from the second wave of the German KORA-Age cohort study collected in 2012. Participation and autonomy was investigated with the Impact on Participation and Autonomy Questionnaire. We used robust regression to analyse the association of vertigo and dizziness with self-perceived participation and autonomy adjusted for covariates. A total of 822 participants (49.6 % female) had a mean age of 78.1 years (SD 6.39). Participation and autonomy were significantly lower in participants with vertigo and dizziness across all domains. Adjusted for age, sex, and chronic conditions, vertigo and dizziness were significantly associated with participation restrictions in all domains except social life and relationships. The results of our study indicate that vertigo and dizziness contribute to restrictions in participation and autonomy in individuals of older age. Recognising vertigo and dizziness as independent contributors to loss of autonomy and decreased chances for independent living may create new options for patient care and population health, such as the designing of complex interventions to maintain participation and autonomy.

To examine the association between electrocardiographic (ECG) findings and disability status in older adults.KORA-Age, a population-based cross-sectional study of the MONICA/KORA project, a randomized sample from Southern Germany of people aged 65 years or older.A total of 534 (51.5%) of 1,037 participants were characterized as disabled. Disabled participants were on average 4.5 years older than those who were not disabled. Crude associations of left-axis deviation, ventricular conduction defects, atrial fibrillation, and QT prolongation with disability status were significant (P0.05). In models controlled for age and sex, these effects remained constant except for QT prolongation. In the models adjusted for the minimal sufficient adjustment set (consisting of the variables sex, physical activity, age, obesity, diabetes, education, heart diseases, income, lung diseases, and stroke) identified by a directed acyclic graph (DAG), no significant association could be shown.Associations between specific ECG findings and disability were found in unadjusted analysis and logistic models adjusted for age and sex. However, when adjusting for other possible confounders identified by the DAG, all these associations were no longer significant. It is important to adequately identify confounding in such settings.

Purpose a population-based study in the region of Augsburg (Germany, KORA) was used to identify the prevalence of eye diseases and their risk factors in a sample of aged individuals. Methods data originated from the KORA-Age study collected in 2012 and 822 participants (49.6% women, 50.4% men, aged 68–96 years) were asked standardised questions about eye diseases. Positive answers were validated and specified by treating ophthalmologists. Additional information came from laboratory data. Polymorphic markers were tested for candidate genes. Results we received validations and specifications for 339 participants. The most frequent eye diseases were cataracts (299 cases, 36%), dry eyes (120 cases, 15%), glaucoma (72 cases, 9%) and age-related macular degeneration (AMD) (68 cases, 8%). Almost all participants suffering from glaucoma or from AMD also had cataracts. Cataract surgery was associated with diabetes (in men; OR = 2.24; 95% confidence interval [CI] 1.11–4.53; P = 0.025) and smoking (in women; OR = 6.77; CI 1.62–28.35; P = 0.009). In men, treatments in airway diseases was associated with cataracts (glucocorticoids: OR = 5.29, CI 1.20–23.37; P = 0.028; sympathomimetics: OR = 4.57, CI 1.39–15.00; P = 0.012). Polymorphisms in two genes were associated with AMD (ARMS2: OR = 2.28, CI 1.48–3.51; P = 0.005; CFH: OR = 2.03, CI 1.35–3.06; P = 0.010). Conclusion combinations of eye diseases were frequent at old age. The importance of classical risk factors like diabetes, hypertension and airway diseases decreased either due to a survivor bias leaving healthier survivors in the older age group, or due to an increased influence of other up to now unknown risk factors. &nbsp

Durch den Anstieg des Anteils alterer Menschen an der Gesamtbevolkerung ist es auch fur die Epidemiologie von besonderem Interesse, welche Faktoren gesundes Altern beeinflussen. 2011 wurde daher innerhalb der Deutschen Gesellschaft fur Epidemiologie (DGEpi) eine Arbeitsgruppe „Epidemiologie des Alterns“ gegrundet. Im Juni 2013 wurde durch die AG ein Workshop organisiert, in dem folgende Datenquellen fur die epidemiologische Alternsforschung in Deutschland vorgestellt wurden: Study of Health in Pomerania (SHIP), Deutscher Alterssurvey (DEAS), Surveys des Robert Koch-Instituts: Studie zur Gesundheit Erwachsener in Deutschland (DEGS) und Gesundheit in Deutschland aktuell (GEDA), Das Sozio-oekonomische Panel (SOEP), Kooperative Gesundheitsforschung in der Region Augsburg (KORA-Age), Survey of Health, Ageing and Retirement in Europe (SHARE) Deutschland, Daten der gesetzlichen Krankenkassen.

Detailed pathophysiological manifestations of early disease in the context of prediabetes are poorly understood. This study aimed to evaluate the extent of early signs of metabolic and cardio-cerebrovascular complications affecting multiple organs in individuals with prediabetes. Subjects without a history of stroke, coronary artery disease, or peripheral artery disease were enrolled in a case-control study nested within the Cooperative Health Research in the Region of Augsburg (KORA) FF4 cohort and underwent comprehensive MRI assessment to characterize cerebral parameters (white matter lesions, microbleeds), cardiovascular parameters (carotid plaque, left ventricular function, and myocardial late gadolinium enhancement [LGE]), and metabolic parameters (hepatic proton-density fat fraction [PDFF] and subcutaneous and visceral abdominal fat). Among 400 subjects who underwent MRI, 103 subjects had prediabetes and 54 had established diabetes. Subjects with prediabetes had an increased risk for carotid plaque and adverse functional cardiac parameters, including reduced early diastolic filling rates as well as a higher prevalence of LGE compared with healthy control subjects. In addition, people with prediabetes had significantly elevated levels of PDFF and total and visceral fat. Thus, subjects with prediabetes show early signs of subclinical disease that include vascular, cardiac, and metabolic changes, as measured by whole-body MRI after adjusting for cardiometabolic risk factors.

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.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.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 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).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.