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BACKGROUND: The acute phase of mycobacterial lung infection is characterized by a nearly exponential outgrowth of mycobacteria in the alveolar airspace and lung parenchymal tissue, suggesting insufficient early protective immunity against mycobacterial challenge. In the current study, we tested the hypothesis that a CC chemokine ligand 2 (CCL2)-dependent increased mononuclear phagocyte subset accumulation in distal airspaces would improve the lungs' protective immunity to infection with Mycobacterium bovis bacille Calmette-Guérin (hereafter, 'M. bovis BCG'). METHODS: Wild-type mice and CCL2-overexpressing mice that exhibited increased pools of alveolar and lung mononuclear phagocytes-due to the lung-specific overexpression of human CCL2 in type-II alveolar epithelial cells-were infected intratracheally with M. bovis BCG and the developing lung inflammatory response was analyzed. RESULTS: CCL2-overexpressing mice demonstrated significantly decreased mycobacterial loads in the bronchoalveolar space, lung parenchymal tissue, and spleen compared with wild-type mice, when both groups of mice were infected with M. bovis BCG. Moreover, in M. bovis BCG-infected mice, later-developing, accelerated resolution of lung granuloma formation was noted, particularly in CCL2-overexpressing mice as compared with wild-type mice. In addition, CCL2-overexpressing mice demonstrated an increased trafficking of mycobacteria-loaded dendritic cells towards lung-draining lymph nodes that was found to coincide with increased mycobacterial loads in this compartment. CONCLUSIONS: The data of the current study suggest that CCL2-dependent amplification of endogenous host-defense programs in the lung may improve the lungs' protective immunity against mycobacterial infections. Copyright © 2008 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

Abstract Background Multimorbidity is a highly frequent condition in older people, but well designed longitudinal studies on the impact of multimorbidity on patients and the health care system have been remarkably scarce in numbers until today. Little is known about the long term impact of multimorbidity on the patients' life expectancy, functional status and quality of life as well as health care utilization over time. As a consequence, there is little help for GPs in adjusting care for these patients, even though studies suggest that adhering to present clinical practice guidelines in the care of patients with multimorbidity may have adverse effects. Methods/Design The study is designed as a multicentre prospective, observational cohort study of 3.050 patients aged 65 to 85 at baseline with at least three different diagnoses out of a list of 29 illnesses and syndromes. The patients will be recruited in approx. 120 to 150 GP surgeries in 8 study centres distributed across Germany. Information about the patients' morbidity will be collected mainly in GP interviews and from chart reviews. Functional status, resources/risk factors, health care utilization and additional morbidity data will be assessed in patient interviews, in which a multitude of well established standardized questionnaires and tests will be performed. Discussion The main aim of the cohort study is to monitor the course of the illness process and to analyse for which reasons medical conditions are stable, deteriorating or only temporarily present. First, clusters of combinations of diseases/disorders (multimorbidity patterns) with a comparable impact (e.g. on quality of life and/or functional status) will be identified. Then the development of these clusters over time will be analysed, especially with regard to prognostic variables and the somatic, psychological and social consequences as well as the utilization of health care resources. The results will allow the development of an instrument for prediction of the deterioration of the illness process and point at possibilities of prevention. The practical consequences of the study results for primary care will be analysed in expert focus groups in order to develop strategies for the inclusion of the aspects of multimorbidity in primary care guidelines.

Historically, viral hepatitis has been a considerable public health problem in Central Asian countries, which may have worsened after the dissolution of the Soviet Union. However, up-to-date seroepidemiological studies are lacking. The aim of the present study was, therefore, to provide current estimates of the seroprevalence of viral hepatitis in Kyrgyzstan, one of the economically least developed countries in the region. We conducted a population-based cross-sectional study in 2018 in the capital of Kyrgyzstan, Bishkek ( n = 1075). Participants, children and adults, were recruited from an outpatient clinic. The data were collected during face-to-face interviews. A blood sample (6 mL) was collected from each participant and tested with ELISA for the presence of serological markers for five viral hepatitides (A, B, C, D, and E). Post-stratification weighing was performed to obtain nationally representative findings. The overwhelming majority of the study participants were positive for anti-HAV (estimated seroprevalence, 75.3%; 95% confidence interval, 72.5-77.9%). The weighted seroprevalence estimates of HBsAg, anti-HCV, and anti-HDV were 2.2% (1.5-3.3%), 3.8% (2.8-5.1%), and 0.40% (0.15-1.01%), respectively. Anti-HEV seropositivity was 3.3% (2.4-4.5%). Of the 33 HBsAg-positive participants, five (15%) were anti-HDV-positive. Our study confirms that Kyrgyzstan remains a highly endemic country for hepatitis virus A and C infections. However, seroprevalences of HBV and HDV were lower than previously reported, and based on these data, the country could potentially be reclassified from high to (lower) intermediate endemicity. The observed anti-HEV seroprevalence resembles the low endemicity pattern characteristic of high-income countries.

Seasonal influenza outbreaks, especially in high-risk groups such as the elderly, represent an important public health problem. Prevailing inadequate efficacy of seasonal vaccines is a crucial bottleneck. Understanding the immunological and molecular mechanisms underpinning differential influenza vaccine responsiveness is essential to improve vaccination strategies. Here we show comprehensive characterization of the immune response of randomly selected elderly participants (≥ 65 years), immunized with the adjuvanted influenza vaccine Fluad. In-depth analyses by serology, multi-parametric flow cytometry, multiplex and transcriptome analysis, coupled to bioinformatics and mathematical modelling, reveal distinguishing immunological and molecular features between responders and non-responders defined by vaccine-induced seroconversion. Non-responders are specifically characterized by multiple suppressive immune mechanisms. The generated comprehensive high dimensional dataset enables the identification of putative mechanisms and nodes responsible for vaccine non-responsiveness independently of confounding age-related effects, with the potential to facilitate development of tailored vaccination strategies for the elderly., (© 2022. The Author(s).)

Purpose: The COVID-19 pandemic affects students in a myriad of different ways. Our prospective, longitudinal study in a cohort of students in Hannover, Germany explores behavioral patterns during escalating COVID-19 restrictions., Methods: In total, 777 students between the age of 9 and 20 were assessed for their activity engagement, travel patterns, and self-assessed compliance with protective recommendations at six time points between June 2020 and June 2021 (3,564 observations) and were monitored for severe acute respiratory syndrome coronavirus 2 infection by nasal swab polymerase chain reaction and serum antibody titers., Results: Activity engagement decreased, but self-assessed compliance with measures such as mask wearing and social distancing was stable during escalating restrictions. Although we found no sex difference during the summer break, when incidence was lowest, females engaged in a higher variety of activities than males for all other time points. Older students engaged in more activities and self-assigned themselves lower compliance values than younger ones. Greater involvement in different activities was seen in households which traveled more frequently. Infection rate in our cohort was low (0.03% acute infections, 1.94% positive seroprevalence)., Discussion: Our study supports the view that, overall, students show high compliance with COVID-19 recommendations and restrictions. The identification of subsets, such as female and older students, with higher risk behavioral patterns should be considered when implementing public information campaigns. In light of the low infection rate in our cohort, we conclude that in-person learning can occur safely if extensive protective measures are in place and the incidence in the general population remains moderate., (Copyright © 2021 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Individuals carrying a pathogenic germline variant in the breast cancer predisposition gene BRCA1 (g BRCA1 +) are prone to developing breast cancer. Apart from its well-known role in DNA repair, BRCA1 has been shown to powerfully impact cellular metabolism. While, in general, metabolic reprogramming was named a hallmark of cancer, disrupted metabolism has also been suggested to drive cancer cell evolution and malignant transformation by critically altering microenvironmental tissue integrity. Systemic metabolic effects induced by germline variants in cancer predisposition genes have been demonstrated before. Whether or not systemic metabolic alterations exist in g BRCA1 + individuals independent of cancer incidence has not been investigated yet. We therefore profiled the plasma metabolome of 72 g BRCA1 + women and 72 age-matched female controls, none of whom (carriers and non-carriers) had a prior cancer diagnosis and all of whom were cancer-free during the follow-up period. We detected one single metabolite, pyruvate, and two metabolite ratios involving pyruvate, lactate, and a metabolite of yet unknown structure, significantly altered between the two cohorts. A machine learning signature of metabolite ratios was able to correctly distinguish between g BRCA1 + and controls in ~82%. The results of this study point to innate systemic metabolic differences in g BRCA1 + women independent of cancer incidence and raise the question as to whether or not constitutional alterations in energy metabolism may be involved in the etiology of BRCA1 -associated breast cancer., Competing Interests: MS was employed by the company Connexome Consulting. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Penkert, Märtens, Seifert, Auber, Derlin, Hille-Betz, Hörmann, Klopp, Prokein, Schlicker, Wacker, Wallaschek, Schlegelberger, Hiller, Ripperger and Illig.)

Background: The immune response to seasonal influenza vaccines decreases with advancing age. Therefore, an adjuvanted inactivated trivalent influenza vaccine (Fluad®) exists for elderly individuals. Fluad® is more immunogenic and efficacious than conventional influenza vaccines. However, the immune response varies and may still result in high frequencies of poor responders. Therefore, we aimed to a) examine the prevalence of a weak response to Fluad® and b) identify potential risk factors., Methods: A prospective population-based study among individuals 65-80 years old was conducted in 2015/2016 in Hannover, Germany (n = 200). Hemagglutination-inhibition titers 21 days after vaccination with Fluad® served as indicator of vaccine responsiveness., Results: The percentage of vaccinees with an inadequate vaccine response varied depending on the influenza strain: it was lowest for H3N2 (13.5%; 95% CI, 9.4-18.9%), intermediate for B strain (37.0%; 30.6-43.9%), and highest for H1N1 (49.0%; 42.2-55.9%). The risk of a weak response to the influenza A H1N1 strain was independently associated with self-reported diabetes (AOR, 4.64; 95% CI, 1.16-18.54), a history of herpes zoster (2.27; 1.01-5.10) and, to a much lesser extent, increasing age (change per year, 1.08; 0.99-1.16). In addition, herpes zoster was the only risk factor for a weak response to the H3N2 antigen (AOR, 3.12; 1.18-8.23). We found no significant association between sex, Body Mass Index, cancer, hypertension, heart attack and CMV seropositivity and a weak response to these two influenza A antigens. Despite its occurence in over one third of vaccinees, none of the variables examined proved to be risk factors for a weak response to the B antigen., Conclusions: A considerable proportion of elderly individuals displayed a weak vaccine response to this adjuvanted seasonal influenza vaccine and further efforts are thus needed to improve immune responses to influenza vaccination among the elderly. Diabetes and herpes zoster were identified as potentially modifiable risk factors for a poor vaccine response against influenza A antigens, but the results also reveal the need for broader investigations to identify risk factors for inadequate responses to influenza B antigens., Trial Registration: No. NCT02362919 (ClinicalTrials.gov, date of registration: 09.02.2015).

Objectives: On the basis of current treatment guidelines, we developed and validated a medication-based chronic disease score (medCDS) and tested its association with all-cause mortality of older outpatients., Study Design and Setting: Considering the most prevalent chronic diseases in the elderly German population, we compiled a list of evidence-based medicines used to treat these disorders. Based on this list, a score (medCDS) was developed to predict mortality using data of a large longitudinal cohort of older outpatients (training sample; MultiCare Cohort Study). By assessing receiver-operating characteristics (ROC) curves, the performance of medCDS was then confirmed in independent cohorts (ESTHER, KORA-Age) of community-dwelling older patients and compared with already existing medication-based scores and a score using selected anatomical-therapeutic-chemical (ATC) codes., Results: The final medCDS score had an ROC area under the curve (AUC) of 0.73 (95% CI 0.70-0.76). In the validation cohorts, its ROC AUCs were 0.79 (0.76-0.82, KORA-Age) and 0.74 (0.71-0.78, ESTHER), which were superior to already existing medication-based scores (RxRisk, CDS) and scores based on pharmacological ATC code subgroups (ATC3) or age and sex alone (Age&Sex)., Conclusions: A new medCDS, which is based on actual treatment standards, predicts mortality of older outpatients significantly better than already existing scores., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: For valid informed consent, it is crucial that patients or research participants fully understand all that their consent entails. Testing and revising informed consent documents with the assistance of their addressees can improve their understandability. In this study we aimed at further developing a method for testing and improving informed consent documents with regard to readability and test-readers' understanding and reactions., Methods: We tested, revised, and retested template informed consent documents for biobank research by means of 11 focus group interviews with members from the documents' target population. For the analysis of focus group excerpts we used qualitative content analysis. Revisions were made based on focus group feedback in an iterative process., Results: Focus group participants gave substantial feedback on the original and on the revised version of the tested documents. Revisions included adding and clarifying explanations, including an info-box summarizing the main points of the text and an illustrative graphic., Conclusion: Our results indicate positive effects on the tested and revised informed consent documents in regard to general readability and test-readers' understanding and reactions. Participatory methods for improving informed consent should be more often applied and further evaluated for both, medical interventions and clinical research. Particular conceptual and methodological challenges need to be addressed in the future.

Elderly individuals have the highest burden of disease from influenza infection but also the lowest immune response to influenza vaccination. A better understanding of the host response to influenza vaccination in the elderly is therefore urgently needed. We conducted a biphasic prospective, population-based study from Dec. 2014 to May 2015 (pilot study) and Sept. 2015 to May 2016 (main study). Individuals 65-80 y of age were randomly selected from the residents' registration office in Hannover, Germany, for the pilot (n = 34) and main study (n = 200). The pilot study tested recruitment for study arms featuring 2, 4, or 5 visits/blood draws. The 5-visit (day 0, 1/3, 7, 21, 70 with respect to vaccination) study arm was selected for the main study. Both studies featured vaccination with Fluad™ (Novartis, Italy), a detailed medical history, a physical exam, recording of adverse events, completion of a questionnaire on common infections and an end-of-study questionnaire, and blood samples. Response rates in the pilot and main studies were 3.7% and 4.0%, respectively. Willingness to participate did not differ among the study arms (Fisher's exact test, p = 0.44). In both studies, there were no losses to follow-up. Compliance with study visits, blood sampling and completion of the questionnaires was very high (100%, >97%, 100%, respectively), as were participants' acceptance of and satisfaction with both phases of the study. The low response rates indicate the need for optimized recruitment strategies if the study population is to be representative of the general population. Nonetheless, the complex prospective study design proved to be highly feasible.

Background: Participation in epidemiological studies has strongly declined in recent years. We examined the reasons for (non)participation in population-based health studies among participants and nonparticipants of a prospective study on influenza vaccination among the elderly., Methods: Males and females between 65 and 80 years of age (N = 5582) were randomly selected from the residents' registration office in Hannover, Germany, and were invited to participate in a study featuring vaccination with a seasonal adjuvanted influenza vaccine (Fluad™, Novartis) including five follow-up visits (day 0, 1/3, 7, 21, 70 with respect to vaccination). A 24-item nonresponder questionnaire, including 10 items on reasons for participating in a hypothetical health study, was mailed to 1500 randomly selected nonparticipants. The same 10 items were included in the end-of-study questionnaire administered to the participants in the vaccination study (n = 200). Logistic regression analysis with backward elimination was used to identify the reasons most strongly associated with nonparticipation., Results: Five hundred thirty-one (35%) nonparticipants and 200 participants (100%) returned the respective questionnaires. Nonparticipation was associated with a lower interest in obtaining personal health information (OR = 3.32) and a preference for less invasive (OR = 3.01) and less time-demanding (OR = 2.19) studies. Responses to other items, e.g. regarding altruistic motives, monetary compensation, general interest of the study, or study approval through ethics committee and data security authority, did not differ between participants and nonparticipants., Conclusions: Participation rates in health studies among elderly individuals could potentially be improved by reducing interventions and time demand, for instance by implementing methods of self-sampling and remote data collection., Trial Registration: No. 1100359 (ClinicalTrials.gov, date of registration: 09.02.2015).

Modern approaches for research with human biospecimens employ a variety of substantially different types of ethics approval and informed consent. In most cases, standard ethics reporting such as "consent and approval was obtained" is no longer meaningful. A structured analysis of 120 biospecimen studies recently published in top journals revealed that more than 85% reported on consent and approval, but in more than 90% of cases, this reporting was insufficient and thus potentially misleading. Editorial policies, reporting guidelines, and material transfer agreements should include recommendations for meaningful ethics reporting in biospecimen research. Meaningful ethics reporting is possible without higher word counts and could support public trust as well as networked research.

Purpose: Care provided in the community for dementia patients on an individual basis may be very time consuming. Yet, little is known about the factors affecting caregiving time for community-dwelling dementia patients. Thus, we aimed to investigate the predictors of informal and formal caregiving time for these patients in a longitudinal approach., Method: Caregiving time for n = 126 community-dwelling dementia patients was assessed by proxy interviews in four assessments at 6-month intervals (1.5 years of longitudinal follow-up; AgeCoDe study). Measurement of informal caregiving time was based on a German adaptation of the Resource Utilization in Dementia questionnaire. Dementia severity was measured by the Clinical Dementia Rating (CDR). We used random effects models to estimate the effects of sociodemographic variables (age, gender, marital status and education), comorbidity and dementia severity on informal and formal caregiving time., Results: At the first assessment, mean age was 85.0 years (±3.2 years). The majority of patients was female (65.9 %), not married (divorced, single, widowed: 55.6 %) and had primary education (63.5 %). Furthermore, mean GDS was 4.4 (±0.8) and mean MMSE was 20.1 (±5.1). According to CDR, 43 individuals had very mild dementia, 55 individuals had mild dementia and 28 individuals had moderate/severe dementia. Moreover, mean total caregiving time was 3.4 h per day (±4.0). Thereof the main part represents informal caregiving time (2.3 h ± 3.4), whereas formal caregiving time was 1.2 h (±2.4). Dementia severity was associated with total caregiving time, mainly influenced by informal caregiving time. Age was positively associated with total caregiving time, driven by formal caregiving time, while being married was positively associated with total caregiving time, mainly affected by informal caregiving time. All need categories of informal caregiving time were strongly related to dementia severity, whereas none of the categories of formal caregiving time were related to dementia severity., Conclusions: Our findings extend previous studies that found an association between informal caregiving time and dementia severity. Moreover, our findings highlight the role of informal care for community-dwelling dementia patients in Germany. Informal caregiving time strongly increases with dementia severity. Consequently, as the number of patients suffering from dementia is expected to increase considerably in the next decades, there is a paramount need to strengthen the informal care system to meet patients' needs.

Biobanks are the basis for a substantial part of biomedical research. The development, establishment and operation of biobanks are connected to a broad range of aspects, mainly concerning the preparation, storage, usage and dissemination of samples and associated data, in addition to the social and public involvement of these processes. These complex requirements can often only be managed in large centralized biobanks. In recent years, centralized clinical biobanks have been established in several university clinics in Germany. Similar activities take place in other European countries and worldwide. This article highlights the requirements and main tasks of centralized clinical biobanks: high-quality pre-analytics and sample storage, the creation of professional IT structures, data protection, ethical issues, in addition to quality and project management.

Objective: Subjective cognitive decline (SCD) might represent the first symptomatic representation of Alzheimer's disease (AD), which is associated with increased mortality. Only few studies, however, have analyzed the association of SCD and mortality, and if so, based on prevalent cases. Thus, we investigated incident SCD in memory and mortality., Methods: Data were derived from the German AgeCoDe study, a prospective longitudinal study on the epidemiology of mild cognitive impairment (MCI) and dementia in primary care patients over 75 years covering an observation period of 7.5 years. We used univariate and multivariate Cox regression analyses to examine the relationship of SCD and mortality. Further, we estimated survival times by the Kaplan Meier method and case-fatality rates with regard to SCD., Results: Among 971 individuals without objective cognitive impairment, 233 (24.0%) incidentally expressed SCD at follow-up I. Incident SCD was not significantly associated with increased mortality in the univariate (HR = 1.0, 95% confidence interval = 0.8-1.3, p = .90) as well as in the multivariate analysis (HR = 0.9, 95% confidence interval = 0.7-1.2, p = .40). The same applied for SCD in relation to concerns. Mean survival time with SCD was 8.0 years (SD = 0.1) after onset., Conclusion: Incident SCD in memory in individuals with unimpaired cognitive performance does not predict mortality. The main reason might be that SCD does not ultimately lead into future cognitive decline in any case. However, as prevalence studies suggest, subjectively perceived decline in non-memory cognitive domains might be associated with increased mortality. Future studies may address mortality in such other cognitive domains of SCD in incident cases.

Background: In older patients with chronic diseases, focusing on subjective, patient-relevant outcomes, such as health-related quality of life (HRQoL), is more pertinent than pursuing clinical or laboratory target values., Aim: To investigate factors influencing the course of HRQoL in older (aged ≥78 years) primary care patients and to derive non-pharmacological recommendations for improving their quality of life., Design and Setting: A population-based prospective longitudinal observational study featuring data analysis from waves 2 to 5 of the AgeCoDe study, which was conducted in six cities in Germany., Method: The HRQoL of 1968 patients over the course of 4.5 years was observed. Patients were, on average, aged 82.6 (±3.4) years and their HRQoL was measured using the EQ-5D visual analogue scale in a face-to-face assessment. Fixed-effects regression models were calculated to examine impact of change in potential influencing factors. This method allows unobserved heterogeneity to be controlled., Results: The course of the participants' HRQoL declined with increasing age, walking and incident hearing impairment. Increasing the number of physical activities improved the HRQoL. These findings were modified by sex, education level, and depression. Especially in females and patients with rather low education levels, increased physical activity improved the subjects' HRQoL, while hearing impairment decreased it. Moving to an institution only improved the HRQoL in patients without depression or those with a low level of education (primary education)., Conclusion: Motivating patients to increase their weekly physical activity and to focus on preserving their ability to walk are promising approaches to improving HRQoL in older age. Less-educated patients and those without depression can also benefit from moving into an institution (for example, a care or retirement home)., (© British Journal of General Practice 2015.)

Purpose: To investigate the coevolution of depression and health-related quality of life (HRQoL) in old age., Methods: In a representative survey of the German general population aged 75 years and older, the course of HRQoL and depression was observed over 4.5 years (3 waves). HRQoL was assessed by the Visual Analogue Scale (EQ VAS) of the EQ-5D instrument, while the Geriatric Depression Scale was used to measure depression. A panel vector autoregressive model was used to account for the complex coevolution of depression and HRQoL. Unobserved heterogeneity was taken into account by taking the first differences., Results: We revealed a robust negative association between an initial change in HRQoL and a subsequent change in depression score, with substantial sex differences: In women there was a robust association, while in men the significance of this association depended on the model specification. Surprisingly, in the total sample and in both sexes, no robust association between an initial increase in depression and a subsequent change in HRQoL was found., Conclusion: Findings indicate that the direction of evolution from HRQoL to depression deserves more attention. Furthermore, treatment of depression in late life should aim at improving HRQoL in which remission of depressive symptoms is necessary but not sufficient.

The aim of the study was to investigate the psychometric properties of a Short Form of the Mini-Mental State Examination (SMMSE) for the screening of dementia in older primary care patients. Data were obtained from a large longitudinal cohort study of initially nondemented individuals recruited via primary care chart registries and followed at 18-month intervals. Item and scale parameters for MMSE and SMMSE scores were analyzed and cross-validated for 2 follow-up assessments (n1 = 2,657 and n2 = 2,274). Binary logistic regression and receiver-operating-characteristic (ROC) curve analyses were conducted in order to assess diagnostic accuracy parameters for MMSE and SMMSE scores. Cross-sectional differentiation between dementia-free and dementia patients yielded moderate to good results for MMSE and SMMSE scores. With regard to most diagnostic accuracy parameters, SMMSE scores did not outperform the MMSE scores. The current study provides first evidence regarding the psychometric properties of the SMMSE score in a sample of older primary care patients. However, our findings do not confirm previous findings that the SMMSE is a more accurate screening instrument for dementia than the original MMSE. Further studies are needed in order to assess and to develop short, reliable and valid instruments for routine cognitive screening in clinical practice and primary care settings., ((c) 2015 APA, all rights reserved.)

Drugs that modify the risk of dementia in the elderly are of potential interest for dementia prevention. Proton pump inhibitors (PPIs) are widely used to reduce gastric acid production, but information on the risk of dementia is lacking. We assessed association between the use of PPIs and the risk of dementia in elderly people. Data were derived from a longitudinal, multicenter cohort study in elderly primary care patients, the German Study on Aging, Cognition and Dementia in Primary Care Patients (AgeCoDe), including 3,327 community-dwelling persons aged ≥ 75 years. From follow-up 1 to follow-up 4 (follow-up interval 18 months), we identified a total of 431 patients with incident any dementia, including 260 patients with Alzheimer's disease. We used time-dependent Cox regression to estimate hazard ratios of incident any dementia and Alzheimer's disease. Potential confounders included in the analysis comprised age, sex, education, the Apolipoprotein E4 (ApoE4) allele status, polypharmacy, and the comorbidities depression, diabetes, ischemic heart disease, and stroke. Patients receiving PPI medication had a significantly increased risk of any dementia [Hazard ratio (HR) 1.38, 95% confidence interval (CI) 1.04-1.83] and Alzheimer's disease (HR 1.44, 95% CI 1.01-2.06) compared with nonusers. Due to the major burden of dementia on public health and the lack of curative medication, this finding is of high interest to research on dementia and provides indication for dementia prevention.

Background: Mean body weight gradually increases with age. Yet, little data exists on the prevalence of excess weight in populations aged 80 years or older. Moreover, little is known about predictors of overweight and obesity in old age. Thus, the purpose of this study was: To present data on the prevalence of excess weight in old age in Germany, to investigate predictors of excess weight in a cross-sectional approach and to examine factors affecting excess weight in a longitudinal approach., Methods: Subjects consisted of 1,882 individuals aged 79 years or older. The course of excess weight was observed over 3 years. Excess weight was defined as follows: Overweight (25 kg/m(2) ≤ BMI < 30 kg/m(2)) and obesity (BMI ≥ 30 kg/m(2)). We used fixed effects regressions to estimate effects of time dependent variables on BMI, and overweight or obesity, respectively., Results: The majority was overweight (40.0%) or obese (13.7%). Cross-sectional regressions revealed that BMI was positively associated with younger age, severe walking impairments and negatively associated with cognitive impairments. Excess weight was positively associated with younger age, elementary education, walking impairments and physical inactivity, while excess weight was negatively associated with cognitive impairment. Longitudinal regressions showed that age and severely impaired walking disabilities reduced BMI. The probability of transitions to excess weight decreased considerably with older age and occurrence of severe walking impairments (overweight)., Conclusions: Marked differences between predictors in cross- and longitudinal setting exist, underlining the complex nature of excess weight in old age.

Type 2 diabetes mellitus (T2DM) is a risk factor of dementia. The effect of T2DM treatment quality on dementia risk, however, is unclear. 1,342 elderly individuals recruited via general practitioner registries (AgeCoDe cohort) were analyzed. This study analyzed the association between HbA1c level and the incidence of all-cause dementia (ACD) and of Alzheimer's disease dementia (referred to here as AD). HbA1c levels ≥6.5% were associated with 2.8-fold increased risk of incident ACD (p = 0.027) and for AD (p = 0.047). HbA1c levels ≥7% were associated with a five-fold increased risk of incident ACD (p = 0.001) and 4.7-fold increased risk of incident AD (p = 0.004). The T2DM diagnosis per se did not increase the risk of either ACD or AD. Higher levels of HbA1c are associated with increased risk of ACD and AD in an elderly population. T2DM diagnosis was not associated with increased risk if HbA1c levels were below 7%.

Background: Social relations and depressive symptoms are intertwined. They both predict subsequent dementia, but only few studies on the association between social life aspects and subsequent dementia exist., Methods: The risk of subsequent dementia was estimated over 2 follow-up assessments, each 18 months apart, depending on leisure activity, social support (general scale and the 3 factors emotional support, practical support, and social integration), and depressive symptoms, using proportional hazard models in a cohort of elderly patients (n = 2,300, with a mean age of 82.45 years) recruited for the study by their general practitioners., Results: Higher depressive symptoms and lower cognitive and physical activity were associated with an increased risk of subsequent all-cause dementia and Alzheimer's dementia (AD). While neither social engagement nor the general social support scale was associated with subsequent dementia, a higher level of social integration was associated with a lower dementia risk. In combined models, the results for activity variables remained similar, but the strength of the association between depressive symptoms and the subsequent risk of dementia decreased, and the association with social integration disappeared., Conclusions: Depressive symptoms increased and activity variables decreased the risk of subsequent dementia; however, activity variables, namely cognitive and physical activity, partly mediated the effect of depressive symptoms on the subsequent risk of all-cause dementia and AD. In many cases, social support was not associated with a risk of subsequent dementia.

Background: In the revised version of the Diagnostic and Statistical Manual of Mental Disorders (DSM) the Mood Disorder Workgroup for DSM-V the bereavement exclusion criterion for the diagnosis of major depression has been eliminated., Aim: To investigate the impact of bereavement on the incidence of depression and depressive symptoms in the elderly., Method: Participants over 75 years from the longitudinal German Study on Ageing, Cognition, and Dementia in Primary Care Patients (AgeCoDe) that were still married at baseline were investigated (n=1,193). Data from four follow-ups (time frame: 6 years) were investigated. The response rate at baseline was 50.3%. Three clinical endpoints were analyzed: depressive symptoms according to Geriatric Depression Scale (1) GDS≥6, (2) GDS≥10, and (3) Major Depression (MD). The effect of loss was investigated using random-effects regression models., Results: Experiencing a loss of spouse was predictive of a higher incidence in GDS≥6 (OR 4.52, 95% CI 2.6-7.9) and 10 (OR 5.59, 95% CI 1.8-17.0) even after adjusting for age, gender, impairment at baseline, and GDS score at baseline. Associations with MD were not significant (OR 1.77, 96% CI 0.9-3.5)., Conclusions: Older adults experiencing the loss of their spouse are more likely to display elevated levels of depressive symptoms, that may reach a concerning level of severity., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Purpose: The concept of mild cognitive impairment (MCI) has recently been introduced into the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) as mild neurocognitive disorder, making it a formal diagnosis. We investigated the prognostic value of such a diagnosis and analyzed the determinants of the future course of MCI in the AgeCoDe study (German Study on Ageing, Cognition, and Dementia in Primary Care Patients)., Methods: We recruited 357 patients with MCI aged 75 years or older from primary care practices and conducted follow-up with interviews for 3 years. Depending on the course of impairment over time, the patients were retrospectively split into 4 groups representing remittent, fluctuating, stable, and progressive courses of MCI. We performed ordinal logistic regression analysis and classification and regression tree (CART) analysis., Results: Overall, 41.5% of the patients had remission of symptoms with normal cognitive function 1.5 and 3 years later, 21.3% showed a fluctuating course, 14.8% had stable symptoms, and 22.4% had progression to dementia. Patients were at higher risk for advancing from one course to the next along this spectrum if they had symptoms of depression, impairment in more than 1 cognitive domain, or more severe cognitive impairment, or were older. The result on a test of the ability to learn and reproduce new material 10 minutes later was the best indicator at baseline for differentiating between remittent and progressive MCI. Symptoms of depression modified the prognosis., Conclusions: In primary care, about one-quarter of patients with MCI have progression to dementia within the next 3 years. Assessments of memory function and depressive symptoms are helpful in predicting a progressive vs a remittent course. When transferring the concept of MCI into clinical diagnostic algorithms (eg, DSM-5), however, we should not forget that three-quarters of patients with MCI stayed cognitively stable or even improved within 3 years. They should not be alarmed unnecessarily by receiving such a diagnosis.

Background/aims: The diagnostic criteria for dementia include reliable evidence of cognitive deterioration over time measured by cognitive tests. The Structured Interview for the Diagnosis of Dementia of the Alzheimer Type, Multi-infarct Dementia and Dementia of other Etiology according to DSM-III-R, DSM-IV and ICD-10 (SIDAM) is a neuropsychological instrument to determine cognitive status in patients with mild cognitive impairment (MCI) and dementia. Normative data for changes in cognitive functioning that normally occur in cognitively healthy individuals are required to interpret changes in SIDAM test scores., Methods: A sample of 1,090 cognitively healthy individuals participating in the German Study on Ageing, Cognition and Dementia in Primary Care Patients (AgeCoDe) aged 75 years and older was assessed four times at 1.5-year intervals over a period of 4.5 years using the SIDAM. Age- and education-specific reliable change indices (RCIs) accounting for probable measurement error and practice effects were computed for a 90% confidence interval., Results: Across different age and education subgroups, changes from at least 3-5 points indicated significant (i.e. reliable) changes in SIDAM test scores at the 90% confidence level., Conclusion: This study offers age- and education-specific normative data for the SIDAM based upon established RCI methods. The RCI scores provided in this study may help clinicians and researchers to interpret cognitive changes in SIDAM test scores and may contribute to the early detection and diagnosis of MCI and dementia in the elderly., (Copyright © 2012 S. Karger AG, Basel.)

Introduction: This study presents a comparison of established methods for measuring dural ectasia with a new quantitative method of assessing this clinical feature., Methods: Seventeen patients with an identified mutation in FBN1 were examined for dural ectasia. The results were compared with 17 age- and sex-matched controls. Our images were also evaluated using the two methods of quantifying dural ectasia, namely those of Ahn et al. and of Oosterhof et al., Results: With our method, 80% MFS1 patients and 7% controls fulfilled the criterion for dural ectasia. Using the method of Oosterhof et al., dural ectasia was found in 88% patients with MFS1 and in 47% controls. Using the method of Ahn et al. 76% patients with Marfan syndrome and 29% controls showed dural ectasia., Conclusion: We present a novel quantitative method of evaluating MRT images for dural ectasia, which, in our own patient cohort, performed better than those previously described.

Objective: Score-based medical urgency criteria are used for necessity-oriented liver transplantation (OLT) but lead to an increasing number of complications in patients with reduced post-OLT survival. A prediction of outcome would improve preoperative patient selection and management., Material and Methods: One-hundred-and-thirty-three consecutive adult patients (63.9% men, mean age 47.4+/-11.2 years) given transplants between May 2004 and November 2005 at the Hannover Medical School were analysed retrospectively using univariate and multivariate methods., Results: Indications were: 27.1% viral hepatitis, 19.6% primary sclerosing cholangitis, 15.0% alcoholic liver disease, 7.5% metabolic liver disease, 6.8% primary biliary cirrhosis. Overall, 12-month patient survival was 81.2%. The mean MELD score at OLT was 14.5+/-5.3 and 12-month survival with MELD >16 (71.7%) and <16 (86.2%) differed significantly (p=0.041). Predictors of 12-month mortality included age (53.2+/-9.4 versus 46.1+/-11.2 years; p=0.004), lower cholinesterase (2.9+/-1.88 versus 3.7+/-2.02 kU/l; p=0.026) and serum creatinine (160.4+/-186.8 versus 77.7+/-31.6 micromol/l; p=0.007), with creatinine and cholinesterase as independent parameters. Based on these parameters, a model for predicting patient survival after liver transplantation was calculated and validated in a second independent cohort of 87 OLT patients. This score identified a high-risk group and a low-risk group (overall survival 47.4 versus 91.2%; p<0.001) with a specificity of 87.3% and a sensitivity of 68.75%., Conclusion: Age, pre-OLT creatinine and cholinesterase are predictors of short-term post-OLT survival and may be helpful as a bedside score in pre-OLT clinical management, outcome prediction and decision-making.