Sex-specific trends in incidence of first myocardial infarction among people with and without diabetes between 1985 and 2016 in a German region.

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.

Public attitudes towards personal health data sharing in long-term epidemiological research: a Citizen Science approach in the KORA study.

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.

Health impact of seven herpesviruses on (pre)diabetes incidence and HbA1c: results from the KORA cohort.

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.

Blood lead levels in 2018/2019 compared to 1987/1988 in the German population-based KORA study.

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.

Impact of prenatal and childhood adversity effects around World War II on multimorbidity: results from the KORA-Age study.

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.

[Sex- and Regionalspecific Differences in Child Abuse and Violence Before the German Reunification. Results from GESA, a Multi-Cohort Study]. / Geschlechts- und regionalspezifische Unterschiede von Kindesvernachlässigung und Gewalt vor der deutschen Wiedervereinigung. Ergebnisse aus GESA, einem Multi-Kohorten Konsortium.

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.

Bidimensional structure and measurement equivalence of the Patient Health Questionnaire-9: sex-sensitive assessment of depressive symptoms in three representative German cohort studies.

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.

Bone marrow fat fraction assessment in regard to physical activity: KORA FF4-3-T MR imaging in a population-based cohort.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. KEY POINTS: • 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.

The times we are born into and our lifestyle choices determine our health trajectories in older age - Results from the KORA-Age study.

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.

Different Psychosocial Factors Are Associated with Seasonal and Perennial Allergies in Adults: Cross-Sectional Results of the KORA FF4 Study.

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.

Being born in the aftermath of World War II increases the risk for health deficit accumulation in older age: results from the KORA-Age study.

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.

BarrettNET-a prospective registry for risk estimation of patients with Barrett's esophagus to progress to adenocarcinoma.

Risk 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.

A Deep Learning Algorithm for Prediction of Age-Related Eye Disease Study Severity Scale for Age-Related Macular Degeneration from Color Fundus Photography.

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: κ 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 κ 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 κ 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 κ outperforming human graders in the AREDS study and is suitable to classify AMD fundus images in other datasets using individuals >55 years of age.

Association between abdominal adiposity and subclinical measures of left-ventricular remodeling in diabetics, prediabetics and normal controls without history of cardiovascular disease as measured by magnetic resonance imaging: results from the KORA-FF4 Study.

OBJECTIVES: Local, abdominal fat depots may be related to alterations in cardiac function and morphology due to a metabolic linkage. Thus, we aimed to determine their association with subtle cardiac changes and the potential interaction with hyperglycemic metabolic states. METHODS: Subjects from the general population and without history of cardiovascular disease were drawn from the Cooperative Health Research in the Region of Augsburg FF4 cohort and underwent 3 T cardiac and body MRI. Measures of abdominal adiposity such as hepatic proton-density fat fraction [PDFFhepatic], subcutaneous (SAT) and visceral abdominal fat (VAT) as well as established cardiac left-ventricular (LV) measures including LV remodeling index (LVCI) were derived. Associations were determined using linear regression analysis based on standard deviation normalized predictors. RESULTS: Among a total of 374 subjects (56.2 ± 9.1 years, 58% males), 49 subjects had diabetes, 99 subjects had prediabetes and 226 represented normal controls. Only subtle cardiac alterations were observed (e.g. LVCI: 1.13 ± 0.30). While SAT was not associated, increasing VAT and increasing PDFFhepatic were independently associated with increasing LVCI (ß = 0.11 and 0.06, respectively), decreasing LV end-diastolic volume (ß = - 6.70 and 3.23, respectively), and decreasing LV stroke volume (ß = - 3.91 and - 2.20, respectively). Hyperglycemic state did not modify the associations between VAT or PDFF and LV measures (interaction term: all p ≥ 0.29). CONCLUSION: In a healthy population, VAT but also PDFFhepatic were associated with subclinical measures of LV remodeling without evidence for a modifying effect of hyperglycemic state.

Association of glycemic status and segmental left ventricular wall thickness in subjects without prior cardiovascular disease: a cross-sectional study.

BACKGROUND: Left ventricular (LV) hypertrophy and changes in LV geometry are associated with increased cardiovascular mortality. Subjects with type 2 diabetes have an increased risk of such alterations in cardiac morphology. We sought to assess the association of glycemic status and LV wall thickness measured by cardiac magnetic resonance (CMR), and potential interactions of hypertension and diabetes. METHODS: CMR was performed on 359 participants from a cross-sectional study nested in a population-based cohort (KORA FF4) free of overt cardiovascular disease. Participants were classified according to their glycemic status as either control (normal glucose metabolism), prediabetes or type 2 diabetes. Segmentation of the left ventricle was defined according to the American Heart Association (AHA) 16-segment model. Measurements of wall thickness were obtained at end-diastole and analyzed by linear regression models adjusted for traditional cardiovascular risk factors. RESULTS: LV wall thickness gradually increased from normoglycemic controls to subjects with prediabetes and subjects with diabetes (8.8 ± 1.4 vs 9.9 ± 1.4 vs 10.5 ± 1.6 mm, respectively). The association was independent of hypertension and traditional cardiovascular risk factors (ß-coefficient: 0.44 mm for prediabetes and 0.70 mm for diabetes, p-values compared to controls: p = 0.007 and p = 0.004, respectively). Whereas the association of glycemic status was strongest for the mid-cavity segments, the association of hypertension was strongest for the basal segments. CONCLUSION: Abnormal glucose metabolism, including pre-diabetes, is associated with increased LV wall thickness independent of hypertension.

Common eye diseases in older adults of southern Germany: results from the KORA-Age study.

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.

Feasibility of a three-step magnetic resonance imaging approach for the assessment of hepatic steatosis in an asymptomatic study population.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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 < 0.0001). All measurements showed excellent correlations (r ≥ 0.9, p < 0.001). Dual-echo Dixon was highly sensitive for the detection of hepatic steatosis (sensitivity 0.97, NPV 0.96) with good specificity and PPV (0.75 and 0.81, respectively). CONCLUSIONS: A multi-step MRI approach may enable rapid and accurate identification of subjects with hepatic steatosis in an asymptomatic population. KEY POINTS: • Dual-echo Dixon can rapidly and reliably exclude hepatic steatosis without complex post-processing. • Multi-echo Dixon and multi-echo spectroscopy yield similar results regarding hepatic fat quantification. • Each sequence can be performed in one breath-hold. • These sequences can be implemented in routine abdominal MRI protocols. • Thus hepatic fat can be evaluated without relevant increase in scan time.

A high level of household physical activity compensates for lack of leisure time physical activity with regard to deficit accumulation: Results from the KORA-Age study.

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 76years, 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.

Prospective association of vitamin D with frailty status and all-cause mortality in older adults: Results from the KORA-Age Study.

OBJECTIVE: To assess the prospective association of serum 25-hydroxyvitamin D [25(OH)D] levels with frailty status and all-cause mortality in a cohort of community-dwelling participants of the population-based KORA [Cooperative Health Research in the Region of Augsburg]-Age Study. METHODS: 727 non-frail participants, aged ≥65years, with 25(OH)D measurement at baseline in 2009, were followed for 2.9±0.1years. Participants were classified as pre-frail or frail if they met 1-2 or ≥3, respectively, of the following five criteria: weight loss, exhaustion, physical inactivity, low walking speed, weakness. The association between 25(OH)D and mortality was assessed in 954 participants. Multivariable adjusted logistic regression models were calculated for each outcome. RESULTS: The incidence of pre-frailty and frailty was 21.2% and 3.9% respectively. After multivariable adjustment, participants with very low 25(OH)D levels (<15ng/ml vs. ≥30ng/ml) had a significantly higher odds for pre-frailty (OR=2.43 [95% CI: 1.17-5.03]) and pre-frailty/frailty combined (OR=2.53 [95% CI: 1.23-5.22]), but not for frailty alone (OR=2.63 [95% CI: 0.39-17.67]). The association between 25(OH)D and mortality (OR=3.39 [95% CI: 1.08-10.65]) was partly mediated by frailty status. CONCLUSION: Very low 25(OH)D levels were independently associated with incident pre-frailty, pre-frailty/frailty combined and all-cause mortality.

Men benefit more from midlife leisure-time physical activity than women regarding the development of late-life disability--results of the KORA-Age study.

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.