Childhood and adolescence factors and multiple sclerosis: results from the German National Cohort (NAKO).

BACKGROUND: Multiple Sclerosis (MS) represents the most common inflammatory neurological disease causing disability in early adulthood. Childhood and adolescence factors might be of relevance in the development of MS. We aimed to investigate the association between various factors (e.g., prematurity, breastfeeding, daycare attendance, weight history) and MS risk. METHODS: Data from the baseline assessment of the German National Cohort (NAKO) were used to calculate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for the association between childhood and adolescence factors and risk of MS. Analyses stratified by sex were conducted. RESULTS: Among a total of 204,273 participants, 858 reported an MS diagnosis. Male sex was associated with a decreased MS risk (HR 0.48; 95% CI 0.41-0.56), while overweight (HR 2.03; 95% CI 1.41-2.94) and obesity (HR 1.89; 95% CI 1.02-3.48) at 18 years of age compared to normal weight were associated with increased MS risk. Having been breastfed for ≤ 4 months was associated with a decreased MS risk in men (HR 0.59; 95% CI 0.40-0.86) compared to no breastfeeding. No association with MS risk was observed for the remaining factors. CONCLUSIONS: Apart from overweight and obesity at the age of 18 years, we did not observe considerable associations with MS risk. The proportion of cases that can be explained by childhood and adolescence factors examined in this study was low. Further investigations of the association between the onset of overweight and obesity in childhood and adolescence and its interaction with physical activity and MS risk seem worthwhile.

Framework and baseline examination of the German National Cohort (NAKO).

The German National Cohort (NAKO) is a multidisciplinary, population-based prospective cohort study that aims to investigate the causes of widespread diseases, identify risk factors and improve early detection and prevention of disease. Specifically, NAKO is designed to identify novel and better characterize established risk and protection factors for the development of cardiovascular diseases, cancer, diabetes, neurodegenerative and psychiatric diseases, musculoskeletal diseases, respiratory and infectious diseases in a random sample of the general population. Between 2014 and 2019, a total of 205,415 men and women aged 19-74 years were recruited and examined in 18 study centres in Germany. The baseline assessment included a face-to-face interview, self-administered questionnaires and a wide range of biomedical examinations. Biomaterials were collected from all participants including serum, EDTA plasma, buffy coats, RNA and erythrocytes, urine, saliva, nasal swabs and stool. In 56,971 participants, an intensified examination programme was implemented. Whole-body 3T magnetic resonance imaging was performed in 30,861 participants on dedicated scanners. NAKO collects follow-up information on incident diseases through a combination of active follow-up using self-report via written questionnaires at 2-3 year intervals and passive follow-up via record linkages. All study participants are invited for re-examinations at the study centres in 4-5 year intervals. Thereby, longitudinal information on changes in risk factor profiles and in vascular, cardiac, metabolic, neurocognitive, pulmonary and sensory function is collected. NAKO is a major resource for population-based epidemiology to identify new and tailored strategies for early detection, prediction, prevention and treatment of major diseases for the next 30 years.

The relationship of skin autofluorescence with diastolic function and HFA-PEFF score in a general population of older people.

BACKGROUND AND AIMS: Advanced glycation end-products accumulation in tissue as measured by Skin autofluorescence (SAF) is related to diastolic function in specific patient populations. This analysis aims at investigating this relationship in a general population of older persons. METHODS AND RESULTS: Based on data from the CARLA cohort at first follow-up, 245 subjects were analyzed and stratified according to cardiovascular risk factors (CVRF). We used linear regression to investigate the association between diastolic function evaluated by echocardiography, HFA-PEFF score, and SAF. Univariable regression analysis showed an association of SAF with septal-E/e' (standardised beta = 1.11, 95% CI = 0.51-1.71) and A (3.42, 95% CI = 0.72-6.12), the former persisting after adjustment for age, sex and CVRF (0.67, 95% CI = 0.05-1.28). Septal-E/e' remained related to SAF only in the high cardiovascular risk stratum (1.16, 95% CI = 0.26-2.06). SAF was related to HFA-PEFF score (0.27, 95% CI = 0.10-0.43) but not after correcting for age and sex (0.16, 95% CI = 0.00-0.32) and CVRF and glomerular filtration rate (0.12, 95% CI = -0.07 - 0.27). SAF was related to the HFA-PEFF score only for participants with high cardiovascular risk (0.23, 95% CI = 0.02-0.45). CONCLUSION: In a general community-dwelling older population, SAF is related to diastolic function as measured by septal-E/e'. Further research is necessary to assess if SAF is a potential screening tool for diastolic dysfunction in advanced age.

Walkability and its association with prevalent and incident diabetes among adults in different regions of Germany: results of pooled data from five German cohorts.

BACKGROUND: Highly walkable neighbourhoods may increase transport-related and leisure-time physical activity and thus decrease the risk for obesity and obesity-related diseases, such as type 2 diabetes (T2D). METHODS: We investigated the association between walkability and prevalent/incident T2D in a pooled sample from five German cohorts. Three walkability measures were assigned to participant's addresses: number of transit stations, points of interest, and impedance (restrictions to walking due to absence of intersections and physical barriers) within 640 m. We estimated associations between walkability and prevalent/incident T2D with modified Poisson regressions and adjusted for education, sex, age at baseline, and cohort. RESULTS: Of the baseline 16,008 participants, 1256 participants had prevalent T2D. Participants free from T2D at baseline were followed over a mean of 9.2 years (SD: 3.5, minimum: 1.6, maximum: 14.8 years). Of these, 1032 participants developed T2D. The three walkability measures were not associated with T2D. The estimates pointed toward a zero effect or were within 7% relative risk increase per 1 standard deviation with 95% confidence intervals including 1. CONCLUSION: In the studied German settings, walkability differences might not explain differences in T2D.

[Occurrence of bronchial asthma and age at initial asthma diagnosis-first results of the German National Cohort]. / Häufigkeit von Asthma bronchiale und Alter bei der Erstdiagnose ­ erste Ergebnisse der NAKO Gesundheitsstudie.

BACKGROUND: Asthma is one of the most common chronic diseases in both children and adults. Asthma first occurring in adulthood (adult-onset asthma, AOA) is associated with poorer prognosis compared to childhood-onset asthma (COA), which urgently calls for more research in this area. The aim of this work was to analyze the data on asthma collected in the German National Cohort and compare it with the German Health Interview and Examination Survey for Adults (DEGS), in particular regarding AOA. MATERIAL AND METHODS: Our analysis was based on the dataset of the main questionnaire at mid-term of the German National Cohort baseline examination, comprising 101,723 participants. Variables considered in the analyses were self-reported diagnosis of asthma, age at first diagnosis, asthma treatment in the past 12 months, age, and sex. RESULTS: In the midterm dataset, 8.7% of women and 7.0% of men in the German National Cohort reported that they had ever been diagnosed with asthma. Approximately one third of participants with asthma received their initial diagnosis before their 18th birthday. COA affected 2.2% of women and 2.8% of men, whereas AOA affected 6.5% of women and 4.2% of men. During the previous 12 months, 33% of COA cases and 60% of AOA cases were medically treated. CONCLUSION: The proportion of persons affected by asthma in the German National Cohort, as well as observed patterns regarding age and gender, corresponds to other data sources such as DEGS. However, in our analysis, the proportion of individuals with AOA was higher than described in the literature. The increase in cumulative asthma diagnoses with age is markedly steeper in younger participants, indicating a rising trend over time.

[Assessment of self-reported cardiovascular and metabolic diseases in the German National Cohort (GNC, NAKO Gesundheitsstudie): methods and initial results]. / Erfassung selbst berichteter kardiovaskulärer und metabolischer Erkrankungen in der NAKO Gesundheitsstudie: Methoden und erste Ergebnisse.

BACKGROUND: Data on self-reported cardiovascular and metabolic diseases are available for the first 100,000 participants of the population-based German National Cohort (GNC, NAKO Gesundheitsstudie). OBJECTIVES: To describe assessment methods and the frequency of self-reported cardiovascular and metabolic diseases in the German National Cohort. MATERIALS AND METHODS: Using a computer-based, standardized personal interview, 101,806 participants (20-75 years, 46% men) from 18 nationwide study centres were asked to use a predefined list to report medical conditions ever diagnosed by a physician, including cardiovascular or metabolic diseases. For the latter, we calculated sex-stratified relative frequencies and compared these with reference data. RESULTS: With regard to cardiovascular diseases, 3.5% of men and 0.8% of women reported to have ever been diagnosed with a myocardial infarction, 4.8% and 1.5% with angina pectoris, 3.5% and 2.5% with heart failure, 10.1% and 10.4% with cardiac arrhythmia, 2.7% and 1.8% with claudicatio intermittens, and 34.6% and 27.0% with arterial hypertension. The frequencies of self-reported diagnosed metabolic diseases were 8.1% and 5.8% for diabetes mellitus, 28.6% and 24.5% for hyperlipidaemia, 7.9% and 2.4% for gout, and 10.1% and 34.3% for thyroid diseases. Observed disease frequencies were lower than reference data for Germany. CONCLUSIONS: In the German National Cohort, self-reported cardiovascular and metabolic diseases diagnosed by a physician are assessed from all participants, therefore representing a data source for future cardio-metabolic research in this cohort.

[Lung function in the German National Cohort: methods and initial results]. / Lungenfunktion in der NAKO Gesundheitsstudie: Methoden und erste Ergebnisse.

BACKGROUND: A nationwide assessment of the respiratory status on the basis of standardized lung function measurements has so far not been available in Germany. The present work describes the lung function tests in the German National Cohort (GNC) and presents initial results based on the GNC Midterm Baseline Dataset. MATERIAL AND METHODS: The assessment of lung function in the GNC comprised spirometry (level 1) and the determination of exhaled nitric oxide (FeNO, level 2). Our quality assurance concept included regular training of lung function test procedures at various GNC sites, interim evaluations of test quality, as well as regular calibration/measurement checks of test equipment. For spirometry, we established a stepwise procedure for offline quality control based on raw flow volume curves. RESULTS: In the present dataset (n = 101,734), spirometry was available for 86,893 study participants and FeNO was available for 15,228 participants. The average (±SD) FEV1 Z score (according to GLI 2012) was -0.321 ± 1.047, the FVC Z score was -0.153 ± 0.941, and the FEV1/FVC Z score was -0.337 ± 0.901. The difference in FEV1/FVC between current smokers and never-smokers increased with age. The average FeNO was 14.2 ÷ 2.0 ppb. Current smoking reduced FeNO levels by 43%, whereas respiratory allergy increased FeNO levels by 16% in nonsmokers. DISCUSSION: The results of spirometry and the FeNO measurements are in the expected range with regard to their distributions and correlates. The GNC provides a valuable basis for future investigations of respiratory health and its determinants as well as research into the prevention of respiratory diseases in Germany.

[Socio-demographic and employment-related factors in the German National Cohort (GNC; NAKO Gesundheitsstudie)]. / Soziodemografische und erwerbsbezogene Merkmale in der NAKO Gesundheitsstudie.

BACKGROUND: In epidemiologic studies, standardised measurement of socio-demographic and employment-related factors is becoming increasingly important, as variables such as gender, age, education or employment status are factors influencing health and disease risks. AIMS: The article gives an overview of the scientific background and assessment of socio-demographic factors in the German National Cohort Study. In addition, the distribution of individual characteristics in the cohort as well as relationships with health-related measures are presented by way of example. MATERIAL AND METHODS: The analysis is based on the data of the first half of the baseline survey (n = 101,724). On this basis, we present the distribution of key socio-demographic characteristics and analyse relationships with exemplary selected health indicators (body mass index, self-reported health) to assess the validity of socio-demographic data measurements. RESULTS: On average, study participants were 52.0 years old (SD = 12.4). Of the participants, 53.6% were women, 54.3% had high education, 60.1% were married and 72% were employed while 3.4% were unemployed. Well-established correlations between socio-demographic factors and health could be reproduced with the German National Cohort data. For example, low education, old age and unemployment were associated with an increased prevalence of obesity and poor self-reported health. DISCUSSION: The German National Cohort provides a comprehensive measurement of socio-demographic characteristics. Combined with a wide range of health data and the longitudinal measurements available in the future, this opens up new opportunities for health science and social epidemiological research in Germany.

[Self-reported cancer in the German National Cohort (NAKO Gesundheitsstudie): assessment methods and first results]. / Selbstberichtete Krebserkrankungen in der NAKO Gesundheitsstudie: Erfassungsmethoden und erste Ergebnisse.

BACKGROUND: In the German National Cohort (NAKO Gesundheitsstudie), the largest prospective cohort study in Germany, data on self-reported cancer diagnoses are now available for the first half of participants. OBJECTIVES: Description of the methods to assess self-reported cancer diagnoses and type of cancer in the NAKO and presentation of first results. MATERIALS AND METHODS: In a computer-assisted, standardized personal interview, 101,787 participants (54,526 women, 47,261 men) were asked whether they had ever been diagnosed with cancer (malignant tumors including in situ) by a physician and how many cancer diagnoses they had. The type of cancer was classified with a list. Absolute and relative frequencies of self-reported cancer diagnoses and types of cancer were calculated and compared with cancer registry data. RESULTS: A physician-diagnosed cancer was reported by 9.4% of women and 7.0% of men. Of the participants who reported a cancer diagnosis, 88.3% reported to have had only one cancer diagnosis. In women, the most frequent malignancies were breast cancer, cervical cancer, and melanoma. In men, the most frequent malignancies were prostate cancer, melanoma, and colorectal cancer. Comparing the frequencies of cancer diagnoses reported by 45- to 74-year-old NAKO participants within the last five years to cancer registry-based 5­year prevalences, most types of cancer were less frequent in the NAKO, with the exception of melanoma in men and women, cervical cancer and liver cancer in women, and bladder cancer and breast cancer in men. CONCLUSIONS: The NAKO is a rich data basis for future investigations of incident cancer.

[Self-reported infections in the German National Cohort (GNC) in the context of the current research landscape]. / Selbst berichtete Infektionen in der NAKO Gesundheitsstudie ­ Einordnung in die gegenwärtige Forschungslandschaft.

BACKGROUND: Infectious diseases continue to play an important role for disease perception, health-economic considerations and public health in Germany. In recent years, infectious diseases have been linked to the development of non-communicable diseases. Analyses of the German National Cohort (GNC) may provide deeper insights into this issue and pave the way for new targeted approaches in disease prevention. OBJECTIVES: The aim was to describe the tools used to assess infectious diseases and to present initial data on infectious disease frequencies, as well as to relate the GNC assessment tools to data collection methods in other studies in Germany. METHODS: As part of the baseline examination, questions regarding infectious diseases were administered using both an interview and a self-administered touchscreen questionnaire. Data from the initial 101,787 GNC participants were analysed. RESULTS: In the interview, 0.2% (HIV/AIDS) to 8.6% (shingles) of respondents reported ever having a medical diagnosis of shingles, postherpetic neuralgia (in cases where shingles was reported), hepatitis B/C, HIV/AIDS, tuberculosis or sepsis if treated in hospital. In the questionnaire, 12% (cystitis) to 81% (upper respiratory tract infections) of respondents reported having experienced at least one occurrence of upper or lower respiratory tract infections, gastrointestinal infections, cystitis or fever within the past 12 months. OUTLOOK: The cross-sectional analyses of data and tools presented here - for example on determinants of susceptibility to self-reported infections - can be anticipated from the year 2021 onward. Beyond that, more extensive research into infectious disease epidemiology will follow, particularly once analyses of GNC biological materials have been performed.

[Nighttime transportation noise annoyance in Germany: personal and regional differences in the German National Cohort Study]. / Nächtliche Verkehrslärmbelästigung in Deutschland: individuelle und regionale Unterschiede in der NAKO Gesundheitsstudie.

BACKGROUND: Noise annoyance is associated with adverse health-related conditions and reduced wellbeing. Thereby, subjective noise annoyance depends on the objective noise exposure and is modified by personal and regional factors. OBJECTIVE: How many participants of the German National Cohort Study (GNC; NAKO Gesundheitsstudie) were annoyed by transportation noise during nighttime and what factors were associated with noise annoyance? MATERIALS AND METHODS: This cross-sectional analysis included 86,080 participants from 18 study centers, examined from 2014 to 2017. We used multinomial logistic regression to investigate associations of personal and regional factors to noise annoyance (slightly/moderately or strongly/extremely annoyed vs. not annoyed) mutually adjusting for all factors in the model. RESULTS: Two thirds of participants were not annoyed by transportation noise during nighttime and one in ten reported strong/extreme annoyance with highest percentages for the study centers Berlin-Mitte and Leipzig. The strongest associations were seen for factors related to the individual housing situation like the bedroom being positioned towards a major road (OR of being slightly/moderately annoyed: 4.26 [95% CI: 4.01;4.52]; OR of being strongly/extremely annoyed: 13.36 [95% CI: 12.47;14.32]) compared to a garden/inner courtyard. Participants aged 40-60 years and those in low- and medium-income groups reported greater noise annoyance compared to younger or older ones and those in the high-income group. CONCLUSION: In this study from Germany, transportation noise annoyance during nighttime varied by personal and regional factors.

[Anthropometric measures in the German National Cohort-more than weight and height]. / Anthropometrische Messungen in der NAKO Gesundheitsstudie ­ mehr als nur Größe und Gewicht.

High levels of adiposity in the population have a major impact on various diseases, but previous epidemiologic studies have largely been restricted to simple anthropometric measures such as the body mass index (BMI), an imperfect predictor of disease risk. There is a critical need for the use of improved measures of relative weight and body composition in large-scale, population-based research.The current article presents initial descriptive results of body composition and fat distribution based on the midterm baseline dataset of the German National Cohort, which included 101,817 participants who were examined in 18 study centers in Germany between March 2014 and March 2017. The anthropometric measures encompassed body weight, height, waist and hip circumference, bioelectrical impedance analysis (BIA), sonography of abdominal adipose tissue, 3D-body scanning, and magnetic resonance imaging.BMI analyses showed that 46.2% of men and 29.7% of women were overweight and 23.5% of men and 21.2% of women were obese. On average, women in almost all age groups demonstrated more subcutaneous adipose tissue layer thickness than men. The mean values of visceral adipose tissue layer thickness, on the other hand, were higher among men than among women in all age groups and increased continuously across age groups in both sexes.The comprehensive assessment of body composition and fat distribution provides novel future opportunities for detailed epidemiologic analyses of overweight and adiposity in relation to the development of chronic diseases.

Advanced glycation end products and their ratio to soluble receptor are associated with limitations in physical functioning only in women: results from the CARLA cohort.

BACKGROUND: Advanced glycation end products (AGEs), modifications of proteins or amino acids, are increasingly produced and accumulated with age-related diseases. Recent studies suggested that the ratio of AGEs and their soluble receptor (sRAGE) is a more accurate biomarker for age-related diseases than each separately. We aim to investigate whether this also applies for physical functioning in a broad age-spectrum. METHODS: AGE and sRAGE levels, and physical functioning (SF-12 questionnaire) of 967 men and 812 women (45-83 years) were measured in the CARLA study. We used ordinal logistic regression to examine associations between AGEs, sRAGE, and AGE/sRAGE ratio with physical functioning in sex- and age-stratified models. RESULTS: Higher levels of AGEs and AGE/sRAGE ratio were associated with lower physical functioning only in women, even after consideration of classical lifestyle and age-related factors (education, BMI, smoking, alcohol consumption, diet, creatinine clearance, diabetes mellitus, lipid lowering and antihypertensive drugs) (odds ratio (OR) =0.86, 95%confidence interval = 0.74-0.98 and OR = 0.86, 95%CI = 0.75-0.98 for AGEs and AGE/sRAGE ratio respectively). We could not demonstrate a significant difference across age. CONCLUSIONS: We showed a sex-specific association between physical functioning and AGEs and AGE/sRAGE, but no stronger associations of the latter with physical functioning. Further investigation is needed in the pathophysiology of this association.

[Assessing incident cardiovascular and metabolic diseases in epidemiological cohort studies in Germany]. / Erfassung inzidenter kardiovaskulärer und metabolischer Erkrankungen in epidemiologischen Kohortenstudien in Deutschland.

BACKGROUND: Cardiovascular and metabolic diseases are a major cause of mortality and loss of quality of life in Germany. Research into risk factors of these diseases requires large population-based cohort studies. Complete and accurate assessment of the incidence of cardiovascular and metabolic diseases is a key element for valid interpretation of the results from such studies. OBJECTIVE: Our aim was to identify population-based cohort studies with incidence of cardiovascular and metabolic diseases in Germany and to summarize their methods for assessment and classification of disease endpoints, including myocardial infarction, type 2 diabetes, stroke, heart failure, and arterial hypertension. METHODS: Within the framework of a workshop, representatives of the ascertained population-based cohort studies in Germany with incidence of cardiovascular or metabolic diseases were invited to present and to systematically provide information on their methods of endpoint identification. RESULTS: We identified eight studies from different regions in Germany with a total of 100,571 participants, aged 18-83 years at baseline. Self-reporting by study participants is the major source for further inquiries to assess disease endpoints in these studies. Most studies use additional data sources to verify the incidence of diseases, such as documents provided by the treating physician or hospital. CONCLUSIONS: Our results highlight the central role of self-reporting and the efforts associated with identification and verification of disease endpoints in cohort studies. They also provide a basis for future population-based studies that aim for standardized assessment of the incidence of cardiovascular and metabolic diseases.

Short-term blood pressure variability - variation between arm side, body position and successive measurements: a population-based cohort study.

BACKGROUND: Precise blood pressure (BP) measurements are central for the diagnosis of hypertension in clinical and epidemiological studies. The purpose of this study was to quantify the variability in BP associated with arm side, body position, and successive measurements in the setting of a population-based observational study. Additionally, we aimed to evaluate the influence of different measurement conditions on prevalence of hypertension. METHODS: The sample included 967 men and 812 women aged 45 to 83 years at baseline. BP was measured according to a standardized protocol with oscillometric devices including three sitting measurements at left arm, one simultaneous supine measurement at both arms, and four supine measurements at the arm with the higher BP. Hypertension was defined as systolic BP (SBP) ≥140 mmHg and/or diastolic BP (DBP) ≥90 mmHg. Variability in SBP and DBP were analysed with sex-stratified linear covariance pattern models. RESULTS: We found that overall, no mean BP differences were measured according to arm-side, but substantial higher DBP and for men also higher SBP was observed in sitting than in supine position and there was a clear BP decline by consecutive measurement. Accordingly, the prevalence of hypertension depends strongly on the number and scheme of BP measurements taken to calculate the index values. CONCLUSIONS: Thus, BP measurements should only be compared between studies applying equal measurement conditions and index calculation. Moreover, the first BP measurement should not be used to define hypertension since it overestimates BP. The mean of second and third measurement offers the advantage of better reproducibility over single measurements.

Predicting risk of substantial weight gain in German adults-a multi-center cohort approach.

Background: A risk-targeted prevention strategy may efficiently utilize limited resources available for prevention of overweight and obesity. Likewise, more efficient intervention trials could be designed if selection of subjects was based on risk. The aim of the study was to develop a risk score predicting substantial weight gain among German adults. Methods: We developed the risk score using information on 15 socio-demographic, dietary and lifestyle factors from 32 204 participants of five population-based German cohort studies. Substantial weight gain was defined as gaining ≥10% of weight between baseline and follow-up (>6 years apart). The cases were censored according to the theoretical point in time when the threshold of 10% baseline-based weight gain was crossed assuming linearity of weight gain. Beta coefficients derived from proportional hazards regression were used as weights to compute the risk score as a linear combination of the predictors. Cross-validation was used to evaluate the score's discriminatory accuracy. Results: The cross-validated c index (95% CI) was 0.71 (0.67-0.75). A cutoff value of ≥475 score points yielded a sensitivity of 71% and a specificity of 63%. The corresponding positive and negative predictive values were 10.4% and 97.6%, respectively. Conclusions: The proposed risk score may support healthcare providers in decision making and referral and facilitate an efficient selection of subjects into intervention trials.

Whole-Body MR Imaging in the German National Cohort: Rationale, Design, and Technical Background.

PURPOSE: To detail the rationale, design, and future perspective of implementing whole-body magnetic resonance (MR) imaging in the German National Cohort, a large multicentric population-based study. MATERIALS AND METHODS: All institutional review boards approved the study, and informed consent is obtained before study enrollment. Participants are enrolled from a random sample of the general population at five dedicated imaging sites among 18 recruitment centers. MR imaging facilities are equipped with identical 3.0-T imager technology and use uniform MR protocols. Imager-specific hardware and software settings remained constant over the study period. On-site and centralized measures of image quality enable monitoring of completeness of the acquisitions and quality of each of the MR sequences. Certified radiologists read all MR imaging studies for presence of incidental findings according to predefined algorithms. RESULTS: Over a 4-year period, six participants per day are examined at each center, totaling a final imaging cohort of approximately 30 000 participants. The MR imaging protocol is identical for each site and comprises a set of 12 native series to cover neurologic, cardiovascular, thoracoabdominal, and musculoskeletal imaging phenotypes totaling approximately 1 hour of imaging time. A dedicated analysis platform as part of a central imaging core incorporates a thin client-based integrative and modular data handling platform to enable multicentric off-site image reading for incidental findings. Scientific analysis will be pursued on a per-project hypothesis-driven basis. CONCLUSION: Population-based whole-body MR imaging as part of the German National Cohort will serve to compile a comprehensive image repository, will provide insight into physiologic variants and subclinical disease burden, and has the potential to enable identification of novel imaging biomarkers of risk.

Pocket depth and bleeding on probing and their associations with dental, lifestyle, socioeconomic and blood variables: a cross-sectional, multicenter feasibility study of the German National Cohort.

BACKGROUND: To investigate the periodontal disease status in a multi-center cross-sectional study in Germany. Associations of dental, socio-economic, blood and biomedical variables with periodontal outcome parameters were evaluated. METHODS: From 4 different centers N = 311 persons were included, drawn randomly from the registration offices. Maximal pocket depth (PD) was used as primary indicator for periodontitis. It was classified as: no/mild ≤3 mm, moderate 4-5 mm, severe ≥6 mm. Associations between socioeconomic (household income, education), lifestyle, and biomedical factors and PD or bleeding on probing (BOP) per site ("Yes"/"No") was analyzed with logistic regression analysis. RESULTS: Mean age of subjects was 46.4 (range 20-77) years. A significantly higher risk of deeper pockets for smokers (OR = 2.4, current vs. never smoker) or persons with higher BMI (OR = 1.6, BMI increase by 5) was found. Severity of periodontitis was significantly associated with caries lesions (p = 0.01), bridges (p < .0001), crowns (p < .0001), leukocytes (p = 0.04), HbA1c (p < .0001) and MCV (p = 0.04). PD was positively correlated with BOP. No significant associations with BOP were found in regression analysis. CONCLUSIONS: Earlier findings for BMI and smoking with severity of PD were confirmed. Dental variables might be influenced by potential confounding factors e.g. dental hygiene. For blood parameters interactions with unknown systemic diseases may exist.

Thyroid analytes TSH, FT3 and FT4 in serum of healthy elderly subjects as measured by the Roche modular system: do we need age and gender dependent reference levels?

BACKGROUND: Age and gender may be involved in the regulation of TSH and thyroid hormones. Reliable investigations concerned with the matter of whether or not these factors are of importance for diagnostic evaluation of the thyroid function are scarce. We used serum values of the CARLA study to calculate reference intervals for TSH, FT3, and FT4 and examine these parameters for their association with age or gender. METHODS: The CARLA study included 967 men and 812 women aged 45 to 83 years. We defined a reference group of 1002 subjects that were free of thyroid disease for data analysis by laboratory analysis and questionnaire, calculated age-dependent moving percentiles (2.5th/97.5th) for TSH, FT4, and FT3 and tested this data set for the confounding factors age and gender. Thereafter, the results were compared to data from the Leipzig Blood Donor study established in 2005. RESULTS: TSH (significant in trend (p = 0.064)) and FT3 (p = 0.001) were inversely associated with age. The correlation of FT3 with age was furthermore influenced by gender (p < 0.001). Neither gender nor age influenced values of FT4. CONCLUSIONS: The decreased TSH and FT3 levels with increasing age suggest a diagnostically relevant modification in the feed back regulation of thyroid function of the elderly. FT3 data should thus be interpreted gender-dependent and even age-dependent for males. These findings should be considered for the diagnostic examination of older patients with suspected disorders of thyroid function.

Educational level, prevalence of hysterectomy, and age at amenorrhoea: a cross-sectional analysis of 9536 women from six population-based cohort studies in Germany.

BACKGROUND: Hysterectomy prevalence has been shown to vary by education level. Hysterectomy influences age at amenorrhoea. The aim of this study was to examine these associations in Germany within population-based data sets. METHODS: Baseline assessments in six population-based cohorts took place from 1997 through 2006 and included 9,548 women aged 20-84 years. All studies assessed hysterectomy history, school and professional degrees. Degrees were categorized into three levels each. Adjusted prevalence ratios and 95% confidence intervals (95% CI) were estimated. RESULTS: Prevalences were higher in West Germany than East Germany, increased by age, and leveled off starting at 55-64 years. The age- and study-adjusted prevalence ratio (lowest versus highest school level) was 2.61 (95% CI: 1.28-5.30), 1.48 (95% CI: 1.21-1.81), and 1.01 (95% CI: 0.80-1.28) for women aged 20-45, 45-64, and 65 and more years respectively. The estimated adjusted prevalence ratios per one unit decrement of the educational qualification score (range 1 = lowest, 8 = highest) were 1.29 (95% CI: 1.02-1.64), 1.08 (95% CI: 1.04-1.12), and 0.98 (95% CI: 0.93-1.03) for women aged 20-44, 45-64, and 65-84 years respectively. Age at amenorrhoea was on average 6.2 years lower (43.5 years versus 49.7 years) among women with a history of hysterectomy than those without. CONCLUSIONS: Lower educational level was associated with a higher hysterectomy prevalence among women aged 20-64 years. Several mediators associated with educational level and hysterectomy including women's disease risk, women's treatment preference, and women's access to uterus-preserving treatment may explain this association. At population level, hysterectomy decreases the age of amenorrhoea on average by 6.2 years.