Characterization of cultural traits and fungicidal activity of strains belonging to the fungal genus Chaetomium.

AIMS: Compare and characterize Chaetomium strains with special regard to their potentialities as biocontrol agents. METHODS AND RESULTS: Twelve strains of the fungal genus Chaetomium from diverse ecological niches were identified as belonging to six different species. Large differences were observed between the strains with regard to temperature requirements for mycelial growth and pigmentation of culture filtrates. Culture filtrates and ethyl acetate extracts were assayed for fungicidal effects against important phytopathogens both on agar media and in multiwell plates. The samples from Chaetomium globosum were particularly active against Botrytis cinerea, Pyrenophora graminea and Bipolaris sorokiniana, while those from C. cochliodes and C. aureum were inhibitory towards Phytophthora infestans, and P. infestans and Fusarium culmorum respectively. To narrow down the active principle, the most promising extracts were separated by preparative HPLC and the resulting fractions tested in bioassays. Chaetoglobosins were identified as active compounds produced by C. globosum. CONCLUSIONS: The bioassays revealed C. aureum and C. cochliodes as promising candidates for use in biocontrol. Both showed remarkably good activity against the prominent plant pathogen P. infestans. SIGNIFICANCE AND IMPACT OF THE STUDY: We provide the first systematic study comparing six different Chaetomium species with regard to their use as biocontrol agents.

Two new species of the Peronospora belbahrii species complex, Pe. choii sp. nov. and Pe. salviae-pratensis sp. nov., and a new host for Pe. salviae-officinalis.

The downy mildew species parasitic to Mentheae are of particular interest, as this tribe of Lamiaceae contains a variety of important medicinal plants and culinary herbs. Over the past two decades, two pathogens, Peronospora belbahrii and Pe. salviae-officinalis have spread globally, impacting basil and common sage production, respectively. In the original circumscription of Pe. belbahrii, the downy mildew of coleus (Plectranthus scutellarioides) was ascribed to this species in the broader sense, but subtle differences in morphological and molecular phylogenetic analyses using two genes suggested that this pathogen would potentially need to be assigned to a species of its own. In the present study, Peronospora species causing downy mildew on members of the Mentheae, including clary sage (Salvia sclarea), meadow sage (S. pratensis), basil (Ocimum basilicum), ground ivy (Glechoma hederacea) and coleus (Plectranthus scutellarioides) were studied using light microscopy and molecular phylogenetic analyses based on six loci (ITS rDNA, cox1, cox2, ef1a, hsp90 and ß-tubulin) to clarify the species boundaries in the Pe. belbahrii species complex. The downy mildew on Salvia pratensis is shown to be distinct from Pe. salviae-officinalis and closely related to Pe. glechomae, and is herein described as a new species, Pe. salviae-pratensis. The downy mildew on S. sclarea was found to be caused by Pe. salviae-officinalis. This is of phytopathological importance, because meadow sage thus does not play a role as inoculum source for common sage in the natural habitat of the former in Europe and Asia, while clary sage probably does. The multi-gene phylogeny revealed that the causal agent of downy mildew on coleus is distinct from Pe. belbahrii on basil, and is herein described as a new taxon, Pe. choii.

Prediction of hospital visits for the general inpatient care using floating catchment area methods: a reconceptualization of spatial accessibility.

BACKGROUND: The adequate allocation of inpatient care resources requires assumptions about the need for health care and how this need will be met. However, in current practice, these assumptions are often based on outdated methods (e.g. Hill-Burton Formula). This study evaluated floating catchment area (FCA) methods, which have been applied as measures of spatial accessibility, focusing on their ability to predict the need for health care in the inpatient sector in Germany. METHODS: We tested three FCA methods (enhanced (E2SFCA), modified (M2SFCA) and integrated (iFCA)) for their accuracy in predicting hospital visits regarding six medical diagnoses (atrial flutter/fibrillation, heart failure, femoral fracture, gonarthrosis, stroke, and epilepsy) on national level in Germany. We further used the closest provider approach for benchmark purposes. The predicted visits were compared with the actual visits for all six diagnoses using a correlation analysis and a maximum error from the actual visits of ± 5%, ± 10% and ± 15%. RESULTS: The analysis of 229 million distances between hospitals and population locations revealed a high and significant correlation of predicted with actual visits for all three FCA methods across all six diagnoses up to ρ = 0.79 (p < 0.001). Overall, all FCA methods showed a substantially higher correlation with actual hospital visits compared to the closest provider approach (up to ρ = 0.51; p < 0.001). Allowing a 5% error of the absolute values, the analysis revealed up to 13.4% correctly predicted hospital visits using the FCA methods (15% error: up to 32.5% correctly predicted hospital). Finally, the potential of the FCA methods could be revealed by using the actual hospital visits as the measure of hospital attractiveness, which returned very strong correlations with the actual hospital visits up to ρ = 0.99 (p < 0.001). CONCLUSION: We were able to demonstrate the impact of FCA measures regarding the prediction of hospital visits in non-emergency settings, and their superiority over commonly used methods (i.e. closest provider). However, hospital beds were inadequate as the measure of hospital attractiveness resulting in low accuracy of predicted hospital visits. More reliable measures must be integrated within the proposed methods. Still, this study strengthens the possibilities of FCA methods in health care planning beyond their original application in measuring spatial accessibility.

Cognitive and emotional empathy in individuals at clinical high risk of psychosis.

BACKGROUND: Impairments of social cognition are considered core features of schizophrenia and are established predictors of social functioning. However, affective aspects of social cognition including empathy have far less been studied than its cognitive dimensions. The role of empathy in the development of schizophrenia remains largely elusive. METHODS: Emotional and cognitive empathy were investigated in large sample of 120 individuals at Clinical High Risk of Psychosis (CHR-P) and compared with 50 patients with schizophrenia and 50 healthy controls. A behavioral empathy assessment, the Multifaceted Empathy Test, was implemented, and associations of empathy with cognition, social functioning, and symptoms were determined. RESULTS: Our findings demonstrated significant reductions of emotional empathy in individuals at CHR-P, while cognitive empathy appeared intact. Only individuals with schizophrenia showed significantly reduced scores of cognitive empathy compared to healthy controls and individuals at CHR-P. Individuals at CHR-P were characterized by significantly lower scores of emotional empathy and unspecific arousal for both positive and negative affective valences compared to matched healthy controls and patients with schizophrenia. Results also indicated a correlation of lower scores of emotional empathy and arousal with higher scores of prodromal symptoms. CONCLUSION: Findings suggest that the tendency to 'feel with' an interaction partner is reduced in individuals at CHR-P. Altered emotional reactivity may represent an additional, early vulnerability marker, even if cognitive mentalizing is grossly unimpaired in the prodromal stage. Different mechanisms might contribute to reductions of cognitive and emotional empathy in different stages of non-affective psychotic disorders and should be further explored.

Associations of area deprivation and urban/rural traits with the incidence of type 1 diabetes: analysis at the municipality level in North Rhine-Westphalia, Germany.

AIM: To analyse the associations of area deprivation and urban/rural traits with the incidence of type 1 diabetes in the German federal state of North Rhine-Westphalia. METHODS: Data of incident type 1 diabetes cases in children and adolescents aged <20 years between 2007 and 2014 were extracted from a population-based diabetes register. Population data, indicators of area deprivation and urban/rural traits at the municipality level (396 entities) were obtained from official statistics. Area deprivation was assessed in five groups based on quintiles of an index of multiple deprivation and its seven deprivation domains. Poisson regression accounting for spatial dependence was applied to investigate associations of area deprivation and urban/rural traits with type 1 diabetes incidence. RESULTS: Between 2007 and 2014, 6143 incident cases were reported (99% completeness); the crude incidence was 22.3 cases per 100 000 person-years. The incidence decreased with increasing employment and environmental deprivation (relative risk of the most vs. the least deprived municipalities: 0.905 [95% CI: 0.813, 1.007] and 0.839 [0.752, 0.937], respectively) but was not associated with the composite deprivation index. The incidence was higher in more peripheral, rural, smaller and less densely populated municipalities, and the strongest association was estimated for the location trait (relative risk of peripheral/very peripheral compared with very central location: 1.231 [1.044, 1.452]). CONCLUSIONS: The results suggest that the type 1 diabetes risk is higher in more remote, more rural, less densely populated and less deprived areas. Urban/rural traits were stronger predictors of type 1 diabetes risk than area deprivation indicators.

Correlation of CSF- and MRI-Biomarkers and Progression of Cognitive Decline in an Open Label MCI Trial.

BACKGROUND: In several randomized controlled trials (RCT) acetylcholinesterase-inhibitors (AChE-I) were tested in patients with mild cognitive impairment (MCI) but were ineffective in delaying disease progression as determined by neuropsychological testing only. Here we present data from an open label observational extension of a multicenter RCT in order to assess if biomarkers are providing useful additional information about a drug's efficacy. We followed 83 amnestic MCI patients and performed correlational analyses of Aß 1-42 and total-Tau in the cerebrospinal fluid (CSF), hippocampal and amygdala volume at baseline, the total duration of blinded and open label AChE-I treatment and the outcome 24 months after inclusion into the RCT. Twelve out of 83 amnestic MCI (14%) had progressed to Alzheimer's disease (AD). Overall, worsening and disease progression as measured by the Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-cog), Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) and Clinical Dementia Rating (CDR) did not correlate with the duration of AChE-I treatment. However, a specific multidimensional biomarker profile at baseline indicated more reliably than cognitive testing alone progression to AD. We conclude that pharmacological RCTs testing symptomatic treatment effects in MCI should include biomarker assessment.

Longitudinal Analysis of Outpatient Physician Visits in the Oldest Old: Results of the AgeQualiDe Prospective Cohort Study.

OBJECTIVES: The aim of this study was to identify determinants of outpatient health care utilization among the oldest old in Germany longitudinally. DESIGN: Multicenter prospective cohort "Study on Needs, health service use, costs and health-related quality of life in a large sample of oldest-old primary care patients (85+)" (AgeQualiDe). SETTING: Individuals in very old age were recruited via GP offices at six study centers in Germany. The course of outpatient health care was observed over 10 months (two waves). PARTICIPANTS: Primary care patients aged 85 years and over (at baseline: n=861, with mean age of 89.0 years±2.9 years; 85-100 years). MEASUREMENTS: Self-reported numbers of outpatient visits to general practitioners (GP) and specialists in the past three months were used as dependent variables. Widely used scales were used to quantify explanatory variables (e.g., Geriatric Depression Scale, Instrumental Activities of Daily Living Scale, or Global Deterioration Scale). RESULTS: Fixed effects regressions showed that increases in GP visits were associated with increases in cognitive impairment, whereas they were not associated with changes in marital status, functional decline, increasing number of chronic conditions, increasing age, and changes in social network. Increases in specialist visits were not associated with changes in the explanatory variables. CONCLUSION: Our findings underline the importance of cognitive impairment for GP visits. Creating strategies to postpone cognitive decline might be beneficial for the health care system.

[Informal care for dementia according to type of service]. / Informelle Pflege bei Demenz nach Leistungsarten.

BACKGROUND: Dementia is a major challenge for society and its impact will grow in the future. Informal care is an essential part of dementia care. Previous studies considered informal care as a whole and not by its components. OBJECTIVE: We aimed to assess the degree of association between specific informal care services and dementia. MATERIAL AND METHODS: This analysis is based on data from the seventh wave of the AgeCoDe/AgeQualiDe study. Dementia was diagnosed based on the DSM-IV criteria. Severity of dementia was assessed and categorized by means of the Clinical Dementia Rating and eight individual informal care services were considered. Logistic regression models were used to assess associations. RESULTS: Of the 864 participants 18% suffered from dementia (very mild: 4%; mild: 6%; moderate: 5%; severe: 3%). All informal care services were significantly associated with dementia, with an emphasis on "supervision", "regulation of financial matters" and "assistance in the intake of medication". Considering different degrees of dementia severity, similar results arose from the analyses. All three aforementioned services showed a pronounced association with all degrees of dementia severity, except for supervision and very mild dementia. CONCLUSION: The provision of all types of informal care services is associated with dementia. The association is pronounced for services that can be more easily integrated into the daily routines of the informal caregiver. Policy makers who plan to integrate informal care into the general care arrangements for dementia should consider this.

[Pharmacogenetics in psychiatry: state of the art]. / Pharmakogenetik in der Psychiatrie: eine Standortbestimmung.

In this article, the current literature on pharmacogenetics of antidepressants, antipsychotics and lithium are summarized by the section of Neurobiology and Genetics of the German Society of Psychiatry, Psychotherapy and Neurology (DGPPN). The publications of international expert groups and regulatory authorities are reviewed and discussed. In Germany, a statement on pharmacogenetics was also made by the gene diagnostics committee of the Ministry of Health. The DGPPN supports two recommendations: 1) to perform CYP2D6 genetic testing prior to prescription of tricyclic antidepressants and 2) to determine the HLA-B*1502 genotype in patients of Asian origin before using carbamazepine. The main obstacle for a broad application of pharmacogenetic tests in psychiatry remains the lack of large prospective studies, for both single gene-drug pair and cobinatorial pharmacogenetic tests, to evaluate the benefits of genetic testing. Psychiatrists, geneticists and funding agencies are encouraged to increase their efforts for the future benefit of psychiatric patients.

Exploring the small-scale spatial distribution of hypertension and its association to area deprivation based on health insurance claims in Northeastern Germany.

BACKGROUND: Hypertension is one of the most frequently diagnosed chronic conditions in Germany. Targeted prevention strategies and allocation of general practitioners where they are needed most are necessary to prevent severe complications arising from high blood pressure. However, data on chronic diseases in Germany are mostly available through survey data, which do not only underestimate the actual prevalence but are also only available on coarse spatial scales. The discussion of including area deprivation for planning of healthcare is still relatively young in Germany, although previous studies have shown that area deprivation is associated with adverse health outcomes, irrespective of individual characteristics. The aim of this study is therefore to analyze the spatial distribution of hypertension at very fine geographic scales and to assess location-specific associations between hypertension, socio-demographic population characteristics and area deprivation based on health insurance claims of the AOK Nordost. METHODS: To visualize the spatial distribution of hypertension prevalence at very fine geographic scales, we used the conditional autoregressive Besag-York-Mollié (BYM) model. Geographically weighted regression modelling (GWR) was applied to analyze the location-specific association of hypertension to area deprivation and further socio-demographic population characteristics. RESULTS: The sex- and age-adjusted prevalence of hypertension was 33.1% in 2012 and varied widely across northeastern Germany. The main risk factors for hypertension were proportions of insurants aged 45-64, 65 and older, area deprivation and proportion of persons commuting to work outside their residential municipality. The GWR model revealed important regional variations in the strength of the examined associations. CONCLUSION: Area deprivation has only a significant and therefore direct influence in large parts of Mecklenburg-West Pomerania. However, the spatially varying strength of the association between demographic variables and hypertension indicates that there also exists an indirect effect of area deprivation on the prevalence of hypertension. It can therefore be expected that persons ageing in deprived areas will be at greater risk of hypertension, irrespective of their individual characteristics. The future planning and allocation of primary healthcare in northeastern Germany would therefore greatly benefit from considering the effect of area deprivation.

[Analysis of the Association between Regional Deprivation and Utilization: An Assessment of Need for Physicians in Germany]. / Analyse des Zusammenhangs zwischen regionaler Deprivation und Inanspruchnahme ­ Ein Diskussionsbeitrag zur Ermittlung des Arztbedarfes in Deutschland.

BACKGROUND: A new strategy for planning outpatient medical care needs to be developed. The social and morbidity structure of the population should be considered in the planning of needs-based provision of medical care. This paper aims to examine the extent to which the degree of regional deprivation can be incorporated in the calculation of the regional requirements for specialists in Germany. METHODS: To measure regional deprivation status at district level, we used the "German Index of Multiple Deprivation" (GIMD) developed in the Helmholtz Zentrum München - German Research Center for Environmental Health. Scores were calculated for the deprivation status of each rural and urban district in Germany. The methods used to compute the deprivation-adjusted medical need are linear regression analyses. The analyses were based on regionalized data for the number of office-based physicians and their billing data. The analyses were carried out with the SPSS software package, version 20. RESULTS: The analyses showed a clear positive correlation between regional deprivation and the utilisation of medical services both for outpatients and in-patients, on the one hand, and mortality and morbidity, as measured by the risk adjustment factor (RSA), on the other. At the district level, the analyses also revealed varying associations between the degree of deprivation and the utilisation of the 12 groups of specialists included in the needs assessment. On this basis, an algorithm was developed by which deprivation at district level can be used to calculate an increase or a decrease in the relative number of specialists needed. DISCUSSION AND CONCLUSION: Using the GIMD and various determinants of medical utilisation, the model showed that medical need increased with the level of regional deprivation. However, regarding SHI medical specialist groups, the associations found in this analysis were statistically (R2) insufficient to suggest a needs assessment planning system based only on the factors analysed, thereby restricting physicians' constitutional right of professional freedom. In particular cases, i. e. licenses to meet special needs, the developed instruments may be suitable for indicating a greater or lesser need for doctors at a regional level due to their relative ease of use and practicability.

New insights into the pharmacogenomics of antidepressant response from the GENDEP and STAR*D studies: rare variant analysis and high-density imputation.

Genome-wide association studies have generally failed to identify polymorphisms associated with antidepressant response. Possible reasons include limited coverage of genetic variants that this study tried to address by exome genotyping and dense imputation. A meta-analysis of Genome-Based Therapeutic Drugs for Depression (GENDEP) and Sequenced Treatment Alternatives to Relieve Depression (STAR*D) studies was performed at the single-nucleotide polymorphism (SNP), gene and pathway levels. Coverage of genetic variants was increased compared with previous studies by adding exome genotypes to previously available genome-wide data and using the Haplotype Reference Consortium panel for imputation. Standard quality control was applied. Phenotypes were symptom improvement and remission after 12 weeks of antidepressant treatment. Significant findings were investigated in NEWMEDS consortium samples and Pharmacogenomic Research Network Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS) for replication. A total of 7062 950 SNPs were analyzed in GENDEP (n=738) and STAR*D (n=1409). rs116692768 (P=1.80e-08, ITGA9 (integrin α9)) and rs76191705 (P=2.59e-08, NRXN3 (neurexin 3)) were significantly associated with symptom improvement during citalopram/escitalopram treatment. At the gene level, no consistent effect was found. At the pathway level, the Gene Ontology (GO) terms GO: 0005694 (chromosome) and GO: 0044427 (chromosomal part) were associated with improvement (corrected P=0.007 and 0.045, respectively). The association between rs116692768 and symptom improvement was replicated in PGRN-AMPS (P=0.047), whereas rs76191705 was not. The two SNPs did not replicate in NEWMEDS. ITGA9 codes for a membrane receptor for neurotrophins and NRXN3 is a transmembrane neuronal adhesion receptor involved in synaptic differentiation. Despite their meaningful biological rationale for being involved in antidepressant effect, replication was partial. Further studies may help in clarifying their role.

Cancer incidence in urban, rural, and densely populated districts close to core cities in Bavaria, Germany.

OBJECTIVE: An ecologic study on the level of districts was performed to evaluate the possible association between district type and risk of cancer in Bavaria, Southern Germany. METHODS: Cancer incidence data for the years 2003-2012 were obtained from the population-based cancer registry Bavaria according to sex and cancer site. Data on district type, socio-economic area deprivation, particulate matter exposure, tobacco consumption, and alcohol consumption were obtained from publicly available sources. The possible association between district type and cancer risk adjusted for age, socio-economic area deprivation, particulate matter exposure, tobacco consumption, and alcohol consumption was evaluated using multivariable multi-level negative binomial regression. RESULTS: We found a significantly reduced cancer risk in densely populated districts close to core cities and/or rural districts compared to core cities with respect to the cancer sites mouth and pharynx (women only), liver (both sexes), larynx (both sexes), lung (both sexes), melanoma of the skin (both sexes), mesothelioma (men only), connective and soft tissue (both sexes), corpus uteri, other urinary tract (men only), urinary bladder (both sexes), and non-Hodgkin lymphoma (both sexes). CONCLUSION: Our findings require further monitoring. Since the apparently increased cancer risk in core cities may be related to lifestyle factors, preventive measures against lifestyle-related cancer could be specifically targeted at populations in deprived core cities.

[A 67-year-old man with fever, night sweat and ascites]. / 67-jähriger Patient mit Fieber, Nachtschweiß und Aszites.

A 67-year-old man presented with fever, night sweat and abdominal complaints for about 4 weeks. Ultrasound and a computed tomography scan showed distinct ascites as the main finding, presenting as exsudate with predominating lymphoid cells. Because of long-term immunosuppressive therapy with the tumor necrosis factor (TNF)-α inhibitor golimumab for psoriasis, the suspicion for a possible tuberculous peritonitis arose. This was confirmed with an enzyme-linked immunospot assay, a high level of adenosine deaminase in the ascites and a peritoneum which was studded with multiple whitish nodules, corresponding to granulomas with giant cells. With a standard antituberculous regimen the symptoms were quickly relieved and finally complete restitution was achieved.

Does Visual Impairment Affect Social Ties in Late Life? Findings of a Multicenter Prospective Cohort Study in Germany.

OBJECTIVE: To investigate how visual impairment affects social ties in late life longitudinally. DESIGN: Population-based prospective cohort study. SETTING: Individuals in old age were recruited via general practitioners' offices (at six study centers) in Germany. They were interviewed every 18 months. PARTICIPANTS: Individuals aged 75 years and above at baseline. Follow-up wave 2 (36 months after baseline, n=2,443) and wave 4 (72 months after baseline, n=1,618) were used for the analyses presented here. MEASUREMENTS: Social ties were assessed using the 14-item form of the questionnaire for social support (F-SozU K-14). Visual impairment was self-rated on a three level Likert scale (no impairment, mild visual impairment, or severe/profound visual impairment). RESULTS: Adjusting for sociodemographic factors, hearing impairment and comorbidity, fixed effects regressions revealed that the onset of mild visual impairment decreased the social support score, in particular the emotional support score. Additionally, the onset of mild hearing impairment decreased the social support score in men. Moreover, increasing age decreased the social support score in the total sample and in both sexes. Loss of spouse and increasing comorbidity did not affect the social support score. CONCLUSION: Our results highlight the importance of visual impairment for social ties in late life. Consequently, appropriate strategies in order to delay visual impairment might help to maintain social ties in old age.

Factors Affecting Functional Impairment among Elderly Germans - Results of a Longitudinal Study.

OBJECTIVE: To investigate causal factors of functional impairment in old age in a longitudinal approach. DESIGN: A population-based prospective cohort study. SETTING: Elderly individuals were recruited via GP offices at six study centers in Germany. They were observed every 1.5 years over six waves. PARTICIPANTS: Three thousand two hundred fifty-six people aged 75 years and older at baseline. MEASUREMENTS: Functional impairment was quantified by the Lawton and Brody Instrumental Activities of Daily Living scale (IADL) and the Barthel-Index (BI). RESULTS: Fixed effects regressions revealed that functional impairment (IADL; BI) increased significantly with ageing (ß=-.2; ß=-1.1), loss of a spouse (ß= .5; ß=-3.1), not living alone in private household (ß=-1.2; ß=-5.5), depression (solely significant for IADL: ß= .6) and dementia (ß=-2.3; ß=-18.2). The comorbidity score did not affect functional impairment. CONCLUSION: Our findings underline the relevance of changes in sociodemographic variables as well as the occurrence of depression or dementia for functional impairment. While several of these causal factors for functional decline in the oldest old are inevitable, some may not be, such as depression. Therefore, developing interventional strategies to prevent depression might be a fruitful approach in order to delay functional impairment in old age.

Genome-wide significant risk factors for Alzheimer's disease: role in progression to dementia due to Alzheimer's disease among subjects with mild cognitive impairment.

Few data are available concerning the role of risk markers for Alzheimer's disease (AD) in progression to AD dementia among subjects with mild cognitive impairment (MCI). We therefore investigated the role of well-known AD-associated single-nucleotide polymorphism (SNP) in the progression from MCI to AD dementia. Four independent MCI data sets were included in the analysis: (a) the German study on Aging, Cognition and Dementia in primary care patients (n=853); (b) the German Dementia Competence Network (n=812); (c) the Fundació ACE from Barcelona, Spain (n=1245); and (d) the MCI data set of the Amsterdam Dementia Cohort (n=306). The effects of single markers and combined polygenic scores were measured using Cox proportional hazards models and meta-analyses. The clusterin (CLU) locus was an independent genetic risk factor for MCI to AD progression (CLU rs9331888: hazard ratio (HR)=1.187 (1.054-1.32); P=0.0035). A polygenic score (PGS1) comprising nine established genome-wide AD risk loci predicted a small effect on the risk of MCI to AD progression in APOE-ɛ4 (apolipoprotein E-ɛ4) carriers (HR=1.746 (1.029-2.965); P=0.038). The novel AD loci reported by the International Genomics of Alzheimer's Project were not implicated in MCI to AD dementia progression. SNP-based polygenic risk scores comprising currently available AD genetic markers did not predict MCI to AD progression. We conclude that SNPs in CLU are potential markers for MCI to AD progression.

[Longitudinal Predictors of the Need for Care]. / Einflussfaktoren auf die Pflegebedürftigkeit im Längsschnitt.

Background: Little is known about the longitudinal predictors of the need for care in old age. However, the knowledge of these factors is important for developing strategies for prevention or delay the need for care. Thus, we aimed at investigating the factors affecting the need for care in old age. Methods: In this population-based prospective cohort study (AgeCoDe, with n=3 217 individuals aged 75 years and above at baseline), the need for care was observed over 4.5 years. The need for care was quantified by the care level defined by the German Law (§ 15 SGB XI). Longitudinal predictors (sociodemographic variables, impairment in mobility/hearing/vision, dementia and depression) of the need for care were examined by using Random Effects Logit regressions. Results: Longitudinal regression analysis revealed that the probability of the need for care significantly increased with the occurrence of dementia (OR: 48.2), mobility impairments (aggravated walking, OR: 26.4; disability of walking, OR: 747.9) and age (e. g. 90 years and above vs.<80 years, OR: 32.3). The influence of family status, living conditions, visual impairment and depression on need for care was markedly smaller, and the effect of hearing impairments did not achieve statistical significance. Conclusion: In order to prevent or delay the need for care in old age, treatments should aim at preserving mobility and cognition. Due to demographic ageing, developing such programs is of major importance for health policy.

Predictors of Frailty in Old Age - Results of a Longitudinal Study.

OBJECTIVES: To investigate time-dependent predictors of frailty in old age longitudinally. DESIGN: Population-based prospective cohort study. SETTING: Elderly individuals were recruited via GP offices at six study centers in Germany. The course of frailty was observed over 1.5 years (follow up wave 4 and follow up wave 5). PARTICIPANTS: 1,602 individuals aged 80 years and older (mean age 85.4 years SD 3.2, with mean CSHA CFS 3.5 SD 1.6) at follow up wave 4. MEASUREMENTS: Frailty was assessed by using the Canadian Study of Health and Aging Clinical Frailty Scale (CSHA CFS), ranging from 1 (very fit) to 7 (severely frail). RESULTS: Fixed effects regressions revealed that frailty increased significantly with increasing age (ß=.2) as well as the occurrence of depression (ß=.5) and dementia (ß=.8) in the total sample. Changes in marital status and comorbidity did not affect frailty. While the effects of depression and dementia were significant in women, these effects did not achieve statistical significance in men. CONCLUSION: Our findings highlight the role of aging as well as the occurrence of dementia and depression for frailty. Specifically, in order to delay frailty in old age, developing interventional strategies to prevent depression might be a fruitful approach.