Search

Objective: To better understand the seemingly contradictory plasma beta-amyloid (Abeta) results in Alzheimer's disease (AD) patients by using a newly developed plasma Abeta assay, the INNO-BIA plasma Abeta forms, in a multicenter study., Methods: A combined retrospective analysis of plasma Abeta isoforms on mild cognitive impairment (MCI) from three large cross-sectional studies involving 643 samples from the participating German and Swedish centers., Results: Detection modules based on two different amino (N)-terminal specific Abeta monoclonal antibodies demonstrated that Abeta in plasma could be reliable quantified using a sandwich immunoassay technology with high precision, even for low Abeta42 plasma concentrations. Abeta40 and Abeta42 concentrations varied consistently with the ApoE genotype, while the Abeta42/Abeta40 ratio did not. Irrespective of the decrease of the Abeta42/Abeta40 ratio with age and MMSE, this parameter was strongly associated with AD, as defined in this study by elevated hyperphosphorylated (P-tau181P) levels in cerebrospinal fluid (CSF)., Conclusion: A highly robust assay for repeatedly measuring Abeta forms in plasma such as INNO-BIA plasma Abeta forms might be a useful tool in a future risk assessment of AD.

Due to the demographic development, the number of dementia patients in Germany is continuously increasing. The complex care situation of those affected calls for meaningful guidelines. In 2008, the first S3 guideline on dementia was published, coordinated by the German Association for Psychiatry, Psychotherapy and Psychosomatics (DGPPN) and the German Association for Neurology (DGN) and accompanied by the Association of the Scientific Medical Societies in Germany (AWMF). An update was published in 2016. In recent years, the diagnostic possibilities for Alzheimer's disease, in particular, have greatly developed and a new disease concept has emerged that includes mild cognitive impairment (MCI) as part of the clinical manifestation of the disease and also enables the diagnosis of Alzheimer's disease in this phase. In the area of treatment, the first causal disease-modifying therapies will likely soon be available. Furthermore, epidemiological studies have also shown that up to 40% of the risks for dementia are dependent on modifiable risk factors, making prevention increasingly more important. In order to do justice to these developments a completely updated S3 guideline on dementia is currently being developed, which will be available digitally for the first time in the form of an app and which, in the sense of living guidelines, will enable rapid adjustments to progress in the future., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

To study the potential diagnostic value of abnormally phosphorylated tau protein in Creutzfeldt-Jakob disease (CJD) compared to Alzheimer's disease (AD), we determined levels of tau phosphorylated at threonine 231 (p-tau231) and of total tau (t-tau) in cerebrospinal fluid (CSF) of CJD patients, AD patients, and healthy controls (HC). CJD patients showed excessively high t-tau levels but relatively low p-tau(231) concentrations compared to the AD group. t-tau alone yielded the best diagnostic accuracy to differentiate between CJD and AD patients, when compared to p-tau231 and the p-tau231/t-tau ratio (97, 78, and 95% correctly allocated cases, respectively). Our findings indicate a dissociation in the direction of change in CSF levels of t-tau and p-tau231 in CJD when compared to AD.

One of the major histopathological hallmarks of Alzheimer's disease (AD) is redundant senile plaques mainly composed of beta-amyloid (Abeta) aggregates. Alternative cleavage of the amyloid precursor protein (APP), occurring in both normal and AD subjects, results in the generation and secretion of soluble APP (sAPP) and Abeta. We examined the cerebrospinal fluid (CSF) for alpha- and beta-secretase cleaved sAPP (alpha-sAPP and beta-sAPP) in 81 sporadic AD patients, 19 patients with mild cognitive impairment, and 42 healthy controls by using newly developed sandwich enzyme-linked immunosorbent assay methods. We found that neither the level of CSF-alpha-sAPP nor CSF-beta-sAPP differed between sporadic AD patients and healthy controls. These findings further support the conclusion that there is no change in APP expression in sporadic AD. However, the level of CSF-beta-sAPP was significantly increased in patients with mild cognitive impairment compared to controls. We also investigated the relationship between the CSF level of alpha/beta-sAPP and Abeta(42) and the apoE epsilon 4 (apoE4) allele. Significantly lower levels of CSF-alpha-sAPP were found in AD patients possessing one or two apoE4 alleles than in those not possessing the apoE4 allele. Neither the levels of CSF-beta-sAPP nor CSF-Abeta(42) differed when comparing ApoE4 allele-positive with allele-negative individuals.

Copyright of People & Nature is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Planted monocultures of even-aged coniferous tree species are abundant worldwide but increasingly damaged by biotic and abiotic stressors and disturbances. In Central Europe, a fundamental goal of ecologically oriented forest management is thus the conversion of pure and often even-aged coniferous stands into structurally more diverse and mixed broad-leaved forests. This conversion is often achieved by single-tree selection resulting in small canopy openings that promote artificial or natural regeneration. Consequently, forest conversion aims at altering stand structure and tree communities. In order to describe the status quo of forest conversion and derive implications for forest management, we investigated changes of tree composition and forest structure in the Bavarian Spessart mountains in southwest Germany. We conducted a resurvey of 108 semi-permanent plots in four different coniferous stand types of Norway spruce, Scots pine, Douglas fir, and European larch about 30 years after the initial survey. We found significant differences in the stratification and cover of respective forest layers between the two sampling periods that indicated an increase in stand structural heterogeneity. While species richness of the overstorey remained constant, species richness and diversity of the shrub and lower canopy layer increased significantly. Regenerating "winner" species included late-successional broad-leaved (e.g., European beech, sessile oak), pioneer broad-leaved (e.g., silver birch, rowan) and shade-tolerant coniferous (e.g., silver fir, Douglas fir) species. Although Norway spruce was significantly reduced in the overstorey, it regenerated in parts extensively in the understorey. We conclude that the forest conversion in the Spessart mountains was overall successful in terms of diversifying forest structure and tree species. Its effects are, though, still emerging and the stands are in a transitional phase. Besides the preferred natural regeneration of target tree species, forest management may consider active measures to guide the facilitated diverse tree community of previously pure and even-aged coniferous stands towards stand maturity. [ABSTRACT FROM AUTHOR]

Natural disasters can affect individuals' views about the environment, especially when these events are extreme and experienced by people directly (locally). In one of the first comprehensive and systematic attempts, we explore whether a similar relationship exists transnationally – a cross‐border effect stemming from environmental disasters abroad on public opinion 'at home'. Spatial analyses present robust evidence that people's environmental salience attitudes are substantially driven by disaster‐related deaths in nearby countries. It follows that environmental disasters cannot be treated as isolated incidents within state borders, but they rather have far‐reaching, transnational consequences on public opinion and, potentially, policy. Accordingly, this research adds to our understanding of environmental politics, public opinion, natural disasters and diffusion effects. [ABSTRACT FROM AUTHOR]

People's perceptions of climate change are crucial for their readiness to engage in mitigation and adaptation. To identify the most influential factors in shaping perceptions of climate change, we conducted a comprehensive survey, carried out in Bavaria, Germany. Overall, 2,594 individuals across four societal actor groups were surveyed, namely 1,413 farmers, 197 foresters, 152 nature managers, and 832 citizens (no specific profession). We explored to what extent environmental factors (climate trends and land cover conditions in interviewees' place of residence -- based on geographical data) and socio-demographic factors (age, gender, education, societal actor group affiliation -- based on survey data) influence perceptions of climate change. Data analyses, including random forest algorithms, revealed socio-demographic factors, particularly societal actor group affiliations, as most influential variables. Local land cover conditions and climate trends only marginally affected residents' perceptions. Consequently, our results suggest to consider socio-demographic factors for tailoring climate communication, policies and awareness raising campaigns, particularly targeting societal groups most skeptical about climate change. [ABSTRACT FROM AUTHOR]

Key message: By calibrating and validating a forest growth model for seven species in Germany and coupling it with a wind damage simulator, we specifically estimated the impact of wind damage on the net present value of Norway spruce and European beech in mixture and monoculture. Under risk, the net present value of spruce managements saw the sharpest declines, although the highest end net present value was still obtained through a heavily thinned spruce monoculture. Context: Wind damage is one of the most important risks to Central European forests, and adaptation measures are essential. Aim: Adaptive management strategies should simultaneously account for forest production and wind risk. We simulated the effect of adaptive measures on wind-risk in German forests. Methods: A process-based forest growth model, "3-PG Mix", was recalibrated and coupled with the storm damage risk model "Lothar". We investigated the effect of thinning regimes on wind risk in monoculture and mixed species stands. The net present value of the simulated regimes was calculated and compared (risk vs. no risk). Results: Spruce regimes achieved the highest net present values when risk was not considered. Considering risk in spruce and beech mixtures and monoculture, all regimes reached values below 3000 € ha−1 by year 120. The exception was a heavily thinned spruce monoculture at 4507 € ha−1, being the most profitable regime under risk. Conclusion: We conclude, on the basis of this modelling study, that heavy thinning reduced storm risk and maintained a higher net present value in spruce. Species mixture of beech and spruce saw net present values levels remain more constant under risk, while beech monoculture increased. [ABSTRACT FROM AUTHOR]

Background: Early detection of dementia provides numerous benefits for those living with dementia and their relatives and healthcare systems at large. Methods available for early diagnosis have improved significantly over the past years. Therefore, we examined whether support for offering an early diagnosis of dementia and willingness to pursue a respective early diagnosis have changed in Germany over the last decade. Method: We compared findings from two representative telephone surveys conducted among older adults in Germany (≥ 60 years of age) in 2011 and 2022, assessing support for offering an early diagnosis of dementia and willingness to pursue a respective early diagnosis in a sample of n = 879 individuals (mean age: 72.9, range: 60–98 years, % female: 58.8). Group comparisons using Chi2- and t-tests and multivariable regression analyses were conducted, regressing support of an early diagnosis of dementia and willingness to pursue a respective early diagnosis on age, gender, education, employment status, belief in preventability of dementia and time of survey. Results: Support for offering an early diagnosis of dementia was high both in 2011 (90.7%) and 2022 (79.2%), but declined over time (OR:.39; 95% CI:.25;.63). Willingness to pursue an early diagnosis of dementia declined from 70.7% to 60.1% in the same period (OR:.62; 95% CI:.45;.86). Belief in preventability of dementia was linked to support for offering an early diagnosis (OR: 1.88, 95% CI: 1.25; 2.83) and willingness to pursue an early diagnosis of dementia (OR: 1.52; 95% CI: 1.12; 2.07). Older participants less often supported offering an early diagnosis of dementia (OR:.97, 95% CI:.95;.99). Conclusion: Support for offering an early diagnosis of dementia and willingness to pursue a respective diagnosis is high in the older German public, but lower than reported previously. Improving knowledge on modifiable risk factors and better understanding of individual motives underlying endorsement or refusal of an early diagnosis may increase acceptance in the general public. [ABSTRACT FROM AUTHOR]

Windstorms are among the primary drivers of forest disturbances. Although they are inherent part of the natural ecosystem processes, they severely impact managed forests. Modeling approaches serve as key tools for the evaluation of disturbance risk and different predisposing factors. However, data availability on relevant forest attributes can be problematic on a larger scale. While spaceborne remote sensing has already proven itself as a tool for disturbance detection, its use in relation to predisposing forest attributes remains underexploited. The present work explores multispectral object-based proxy predictors for statistical wind disturbance modeling based on the publicly available Sentinel-2 imagery and recorded damage polygons from the pan-European FORWIND database. Potential predictors were tested in logistic and random forests (RF) regression models for both disturbance occurrence and severity for a case study of a major storm event in Northern Germany from 2017. The results reveal a general potential of the derived spaceborne variables to be used as proxy variables to critical predisposing forest attributes. The presented proxy variables also outperformed a set of publicly available derived spatial data products for modeling both disturbance occurrence and severity. Model accuracies were moderate (reaching AUC = 0.76 for logistic regression fit and AUC = 0.69 for predictive accuracy of RF models), yet falling within the range of reported results in previous studies from the field. Limitations of the spectral satellite imagery as a single information source were acknowledged; however, the results indicate the further potential of spaceborne imagery applications in disturbance modeling, assessment and resulting mapping of disturbance susceptibility at different spatial scales. Considering the growing spatiotemporal availability of high-resolution spaceborne data, we propose that a model representation of post-disturbance forest patterns could improve the understanding of complex disturbance regimes and recurrent susceptibility. [ABSTRACT FROM AUTHOR]

Introduction: Transcranial pulse stimulation (TPS) is a non-invasive neuromodulation therapy that uses short, repetitive shockwaves through a neuro-navigated device. Current research suggests that these pulses lead to a wide range of vascular, metabolic, and neurotrophic changes. This relatively new CE-marked treatment provided first promising results in a clinical pilot study for improving cognition in mild-to-moderate Alzheimer's. Data from other centers is lacking, so here we analyzed safety and pilot real-world short-term results of TPS from the first center in Germany. To gain information about effects in different stages, patients with not only mild but also moderate-to-severe Alzheimer's were analyzed. Methods: A total of 11 patients were retrospectively examined for cognitive and emotional function before and after the first stimulation series. The effect was assessed using several neuropsychological tests [Alzheimer's Disease Assessment Scale (ADAS), including the ADAS cognitive score (ADAS Cog) and ADAS affective scores, Mini-Mental Status Examination (MMSE), and Montreal Cognitive Assessment (MoCA)] including in comparison between the groups of mild-to-severe patients. Moreover, subjective improvement of symptom severity, potential effects on depressive symptoms, and side effects were analyzed using Numeric Rating Scales (NRS). Results: Side effects were rare (in 4% of sessions) with moderate subjective severity and only transient. Patients significantly improved in the ADAS and ADAS Cog, while there was no significant effect in MMSE and MoCA. Patients' self-reported symptom severity improved significantly. The depressive symptoms measured in an ADAS subscale also improved significantly. Statistical data analyses revealed no significant correlation of clinical improvement with baseline symptom severity. Conclusion: TPS might be a safe and promising add-on therapy for Alzheimer's, even for moderate-to-severe patients. More research on long-term effects in patients as well as studies with sham control groups is needed. Moreover, translational research on the mechanisms of action and effects on cerebral network physiology will be needed to understand this new neuromodulation technique. [ABSTRACT FROM AUTHOR]

Trees along railway networks represent a high risk due to their potential to fall during extreme weather events. The identification of locations along railway tracks with highest tree fall hazard is an important part of a proactive natural hazard management. A new user-friendly GIS tool (as ArcGIS toolbox) was developed that provides the opportunity to detect individual trees along railway lines and to estimate the hazard of tree fall. By an automated analysis of open source digital remote sensing data and additional open source geodata, the tool allows for an up-to-date and area-wide monitoring of trees on railway lines and other infrastructural elements. Important parameters describing meteorological conditions, site conditions, topographic conditions and tree characteristics are implemented. The tool was successfully tested and applied to two federal states in Germany (Northrhine-Westphalia and Thuringia). Due to the automatization of most of the processes, it is possible to extend the application to larger areas with low effort, i.e., to the Germany-wide rail network or to other countries. It is also possible to perform the analysis for other modes of transport. In the context of natural hazard management, the tool can be applied in prevention and can usefully support already existing vegetation management concepts. [ABSTRACT FROM AUTHOR]

Introduction Subjective cognitive decline (SCD) is an established precursor of dementia. However, the relationship between SCD and dementia has been mostly studied among people aged 65+. We aimed to assess the association between subjective memory difficulties at ages 50–75 with all-cause dementia and dementia-subtypes in a community-based cohort with long-term follow-up. Methods 6,190 individuals (51% female) aged 50–75 years (median age, 62) attending a general health examination (by a total of 684 general practitioners) in Saarland, Germany, in 2000–2002 were recruited for a community-based cohort study. Subjective difficulties regarding short-term and long-term memory were assessed at baseline with two simple yes/no questions. Associations with dementia (−subtypes) diagnoses during 17 years of follow-up were estimated by Cox proportional hazards models. Results 492 participants were diagnosed with dementia during 17 years of follow-up. Participants with short-term memory difficulties were at higher risk to receive incident all-cause dementia and vascular dementia diagnoses both within 0–9 years (age and sex adjusted hazard ratios (aHR), 1.80 and 2.00, respectively) and within 0–17 years (aHR 1.55 and 1.78, respectively) from recruitment (P  < 0.05 in all cases). For clinical Alzheimer's disease, a significant association was only seen within the initial 6 years. There were no associations of long-term memory difficulties with any type of dementia. Conclusions Subjective difficulties in short-term memory predict both intermediate and long-term risk of vascular and all-cause dementia even among late middle-age adults. These results underline the importance of cardiovascular disease prevention efforts well before old age for maintaining cognitive health. [ABSTRACT FROM AUTHOR]

Background: Subjective cognitive decline (SCD) is considered as the first symptomatic manifestation of Alzheimer's disease (AD), which is also affected by different cultural backgrounds. Establishing cross-cultural prediction models of SCD is challenging.Objective: To establish prediction models of SCD available for both the Chinese and European populations.Methods: In this project, 330 SCD from China and 380 SCD from Germany are intended to be recruited. For all participants, standardized assessments, including clinical, neuropsychological, apolipoprotein E (APOE) genotype, blood, and multi-parameter magnetic resonance imaging (MRI) at baseline will be conducted. Participants will voluntarily undergo amyloid positron emission tomography (PET) and are classified into amyloid-β (Aβ) positive SCD (SCD+) and Aβ negative SCD (SCD-). First, baseline data of all SCD individuals between the two cohorts will be compared. Then, key features associated with brain amyloidosis will be extracted in SCD+ individuals, and the diagnosis model will be established using the radiomics method. Finally, the follow-up visits will be conducted every 12 months and the primary outcome is the conversion to mild cognitive impairment or dementia. After a 4-year follow-up, we will extract factors associated with the conversion risk of SCD using Cox regression analysis.Results: At present, 141 SCD from China and 338 SCD from Germany have been recruited. Initial analysis showed significant differences in demographic information, neuropsychological tests, and regional brain atrophy in SCD compared with controls in both cohorts.Conclusion: This project may be of great value for future implications of SCD studies in different cultural backgrounds.Trial Registration: ClinicalTrials.gov, NCT04696315. Registered 3 January 2021. [ABSTRACT FROM AUTHOR]

Observational evidence suggests that forests in the Northern Alps are changing at an increasing rate as a consequence of climate change. Yet, it remains unclear whether the acceleration of forest change will continue in the future, or whether downregulating feedbacks will eventually decouple forest dynamics from climate change. Here we studied future forest dynamics at Berchtesgaden National Park, Germany by means of a process‐based forest landscape model, simulating an ensemble of 22 climate projections until the end of the 21st century. Our objectives were (i) to assess whether the observed acceleration of forest dynamics will continue in the future, (ii) to analyze how uncertainty in future climate translates to variation in future forest disturbance, structure, and composition, and (iii) to determine the main drivers of future forest dynamics. We found that forest dynamics continue to accelerate in the coming decades, with a trend towards denser, structurally more complex and more species rich forests. However, changes in forest structure leveled off in the second half of the 21st century regardless of climate scenario. In contrast, climate scenarios caused trajectories of tree species change to diverge in the second half of the 21st century, with stabilization under RCP 2.6 and RCP 4.5 scenarios and accelerated loss of conifers under RCP 8.5. Disturbance projections were 3 to 20 times more variable than future climate, whereas projected future forest structure and composition varied considerably less than climate. Indirect effects of climate change via alterations of the disturbance regime had a stronger impact on future forest dynamics than direct effects. Our findings suggest that dampening feedbacks within forest dynamics will decelerate forest change in the second half of the 21st century. However, warming beyond the levels projected under RCP 4.5 might profoundly alter future forest disturbance and composition, challenging conservation efforts and ecosystem service supply. [ABSTRACT FROM AUTHOR]

Background: Cerebrospinal fluid (CSF) analysis for detecting amyloid positivity may be as reliable as positron emission tomography (PET). We evaluated the performance of the amyloid beta (Aβ)42/40 ratio for predicting amyloid positivity by PET, compared with Aβ42 alone, and phosphorylated tau 181 (pTau181)/Aβ42 and total tau (tTau)/Aβ42 ratios, using fully automated CSF immunoassays (Roche Diagnostics International Ltd, Rotkreuz, Switzerland) in a heterogeneous cohort of patients with a range of cognitive disorders reflecting the typical population of a memory clinic. Methods: CSF samples from 103 patients with known amyloid PET status (PET positive = 54; PET negative = 49) were retrospectively selected from one site in Germany; 71 patients were undergoing treatment for mild cognitive impairment (n = 44) or mild-to-moderate dementia (n = 27) due to Alzheimer's disease (AD), and 32 patients were undergoing treatment for non-AD-related cognitive disorders. Aβ42, pTau181, and tTau concentrations were measured in CSF samples using the respective Elecsys® CSF immunoassays modified for use on the cobas e 411 analyzer; Aβ40 concentrations were measured using a non-commercially available robust prototype assay. Sensitivities/specificities for amyloid positivity cut-offs (Youden-derived and pre-defined) were calculated, and receiver operating characteristic analyses determined area under the curve (AUC) versus amyloid PET status. Limitations include a small sample size, use of a pre-analytical protocol not in accordance with the Elecsys CSF immunoassay method sheets, and the lack of a pre-defined cut-off for Aβ42/40. Results: Point estimates for sensitivity and specificity of CSF biomarkers and biomarker ratios versus amyloid PET were 0.93 and 0.57 for Aβ42, 0.96 and 0.69 for pTau181/Aβ42, 0.92 and 0.69 for tTau/Aβ42, and 0.94 and 0.82 for Aβ42/40. For AUCs, point estimates (95% confidence intervals) versus amyloid PET were 0.78 (0.68−0.88) for Aβ42, 0.88 (0.81−0.95) for pTau181/Aβ42, 0.87 (0.80−0.95) for tTau/Aβ42, and 0.90 (0.83−0.97) for Aβ42/40. Conclusions: CSF Aβ42/40 ratio can predict PET amyloid positivity with high accuracy in patients with a range of cognitive disorders when evaluating Aβ pathology independent of tau and neurodegeneration for research purposes. The performance of Aβ42/40 was comparable with pTau181/Aβ42 and tTau/Aβ42 used in clinical practice and better than Aβ42 alone. [ABSTRACT FROM AUTHOR]

Climate change is producing threats to forests' capacity of regulating water regimes. Therefore, thinning strategies can be applied to mitigate climate change impacts more efficiently by providing more spaces for trees to utilize resources e.g., water and nutrients. This study examined the effects of different thinning intensities and intervals on water characteristics and biomass growth of a 75-year-old Norway spruce (Picea abies) stand in the Black Forest, Germany. Here we used a water and management sensitive update of the process-based forest growth model 3PG, 3PG-Hydro. We applied light (10%), moderate (30%), and heavy thinning (50% intensity) in the interval of 10, 25, and 50 years of the management period. We simulated growth with climate change scenario RCP 8.5 data from 1995 to 2065. We analyzed the effects of the different thinning regimens on biomass, evapotranspiration as well as water yield. Thinning intensity and interval as well as their interaction have significant influence on production of stand biomass and water yield for all thinning regimes applied (p < 0.05). However, there is no significant difference (p > 0.05) in accumulated biomass (thinned biomass added to the stand biomass) between the applied thinning regimes. Light thinning in a long interval (50 years) produced highest stand biomass among the applied thinning regimes. Furthermore, the prediction showed that accumulated water yield increased with increasing thinning intensity. Our study concludes that repeated moderate thinning at intermediate intervals results in a high water yield without losing biomass production. [ABSTRACT FROM AUTHOR]

Background: To evaluate the diagnostic accuracy of cerebrospinal fluid (CSF) biomarkers in patients with probable cerebral amyloid angiopathy (CAA) according to the modified Boston criteria in a retrospective multicentric cohort. Methods: Beta-amyloid 1-40 (Aβ40), beta-amyloid 1-42 (Aβ42), total tau (t-tau), and phosphorylated tau 181 (p-tau181) were measured in 31 patients with probable CAA, 28 patients with Alzheimer's disease (AD), and 30 controls. Receiver-operating characteristics (ROC) analyses were performed for the measured parameters as well as the Aβ42/40 ratio to estimate diagnostic parameters. A meta-analysis of all amenable published studies was conducted. Results: In our data Aβ42/40 (AUC 0.88) discriminated best between CAA and controls while Aβ40 did not perform well (AUC 0.63). Differentiating between CAA and AD, p-tau181 (AUC 0.75) discriminated best in this study while Aβ40 (AUC 0.58) and Aβ42 (AUC 0.54) provided no discrimination. In the meta-analysis, Aβ42/40 (AUC 0.90) showed the best discrimination between CAA and controls followed by t-tau (AUC 0.79), Aβ40 (AUC 0.76), and p-tau181 (AUC 0.71). P-tau181 (AUC 0.76), Aβ40 (AUC 0.73), and t-tau (AUC 0.71) differentiated comparably between AD and CAA while Aβ42 (AUC 0.54) did not. In agreement with studies examining AD biomarkers, Aβ42/40 discriminated excellently between AD and controls (AUC 0.92–0.96) in this study as well as the meta-analysis. Conclusion: The analyzed parameters differentiate between controls and CAA with clinically useful accuracy (AUC > ∼0.85) but not between CAA and AD. Since there is a neuropathological, clinical and diagnostic continuum between CAA and AD, other diagnostic markers, e.g., novel CSF biomarkers or other parameters might be more successful. [ABSTRACT FROM AUTHOR]

In the absence of effective pharmacological therapy options, the focus of dementia and Alzheimer's research has shifted from treatment and care to risk prediction, early detection, and prevention. Public health communication and media coverage regarding dementia emphasize the individual responsibility for dementia risk management. Focusing on the social and moral implications of the new understanding and public representation of dementia, we present an analysis of medical science, nursing science, and media discourses in Germany between 2014 and 2019. We show which notions of dementia and prevention characterize the medical and nursing science debates regarding dementia and how scientific knowledge is transferred into media discourses on dementia. We further discuss how dementia risk communication interacts with contemporary social and health policies and in what ways current dementia discourses are associated with a (self-)responsibilization of cognitive aging. [ABSTRACT FROM AUTHOR]

Background: To understand the potential for early intervention and prevention measures in Alzheimer's disease, the association between risk factors and early pathological change needs to be assessed. Hence, the aim of this study was to determine whether risk factors of Alzheimer's clinical syndrome (clinical AD), such as body mass index (BMI), are associated with Aβ misfolding in blood, a strong risk marker for AD among older adults. Methods: Information on risk factors and blood samples were collected at baseline in the ESTHER study, a population-based cohort study of older adults (age 50–75 years) in Germany. Aβ misfolding in blood plasma was analyzed using an immuno-infrared-sensor in a total of 872 participants in a nested case-control design among incident dementia cases and matched controls. Associations between risk factors and Aβ misfolding were assessed by multiple logistic regression. For comparison, the association between the risk factors and AD incidence during 17 years of follow-up was investigated in parallel among 5987 cohort participants. Results: An inverse association with Aβ misfolding was seen for BMI at age 50 based on reported weight history (aOR 0.64, 95% CI 0.43–0.96, p = 0.03). Similar but not statistically significant associations were seen for BMI at baseline (i.e., mean age 68) and at age 40. No statistically significant associations with Aβ misfolding were found for other risk factors, such as diabetes, smoking, and physical activity. On the other hand, low physical activity was associated with a significantly reduced risk of developing clinical AD compared to physical inactivity. Conclusions: Our results support that AD pathology may be detectable and associated with reduced weight even in middle adulthood, many years before clinical diagnosis of AD. Physical activity might reduce the risk of onset of AD symptoms. [ABSTRACT FROM AUTHOR]

There is growing evidence that promising biomarkers of inflammation in Alzheimer´s disease (AD) and other neurodegenerative diseases correlate strongest to levels of tau or neurofilament, indicating an inflammatory response to neuronal damage or death. To test this hypothesis, we investigated three AD candidate markers (ferritin, fatty acid binding protein 3 (FABP‐3), and neurogranin) in interrelation to established AD and inflammatory protein markers. We further aimed to determine if such interrelations would be evident in pathological subjects only or also under non‐pathological circumstances. Cerebrospinal fluid levels of the three proteins were quantified in samples from the University Clinic of Bonn (UKB) Department of Neurodegenerative Diseases & Geriatric Psychiatry, Germany. Data were analyzed based on clinical or biomarker‐defined stratification of subjects with adjustment for covariates age, sex, and APOE status. Levels of ferritin, FABP‐3 and neurogranin were elevated in subjects with pathological levels of t‐tau independent of beta‐amyloid status. The three markers correlated with each other, tau isoforms, age, and those inflammatory markers previously described as related to neurodegeneration, predominantly sTREM2, macrophage migration inhibitory factor, soluble vascular endothelial growth factor receptor, soluble vascular cell adhesion molecule 1 (sVCAM‐1), and C1q. These interrelations existed in subjects with pathological and sub‐pathological tau levels, in particular for FABP‐3 and neurogranin. Relations to ferritin were independent of absolute levels of tau, too, but showed differing trajectories between pathological and non‐pathological subjects. A specific set of inflammatory markers is highly related to markers of neuronal damage such as tau, neurogranin, or FABP‐3. These proteins could be used as readouts of the inflammatory response during the neurodegeneration phase of AD. [ABSTRACT FROM AUTHOR]

Background and purpose: Clinical diagnostic criteria for neurodegenerative diseases have been framed based on clinical phenomenology. However, systematic knowledge about the first reported clinical symptoms in neurodegenerative diseases is lacking. Therefore, the aim was to determine the prevalence and clinical implications of the first clinical symptom (FS) as assessed by medical history in neuropathologically proven neurodegenerative diseases. Methods: Neuropathological diagnoses from the Neurobiobank Munich, Germany, were matched with clinical records for analyses of the diagnostic and prognostic values of FSs. Results: In all, 301 patients with the neuropathological diagnoses Alzheimer disease (AD), progressive supranuclear palsy (PSP), frontotemporal lobar degeneration (FTLD), Lewy body disease (LBD) including the neuropathologically indistinguishable clinical phenotypes Parkinson disease and dementia with Lewy bodies, multiple system atrophy (MSA) and corticobasal degeneration (CBD) were studied. Memory disturbance was the most common FS in AD (34%), FTLD (19%) and LBD (26%), gait disturbance in PSP (35%) and MSA (27%) and aphasia and personality changes in CBD (20%, respectively). In a model adjusting for prevalence in the general population, AD was predicted by memory disturbance in 79.0%, aphasia in 97.2%, personality changes in 96.0% and by cognitive disturbance in 99.0%. Gait disturbance and tremor predicted LBD in 54.6% and 97.3%, coordination disturbance MSA in 59.4% and dysarthria FTLD in 73.0%. Cognitive FSs were associated with longer survival in AD (12.0 vs. 5.3 years; p < 0.001) and FTLD (8.2 vs. 4.1 years; p = 0.005) and motor FSs with shorter survival in PSP (7.2 vs. 9.7; p = 0.048). Conclusions: Assessing FSs in neurodegenerative diseases may be beneficial for accuracy of diagnosis and prognosis and thereby may improve clinical care and precision of study recruitment. [ABSTRACT FROM AUTHOR]

Background: The focus on early detection of dementia and Mild Cognitive Impairment (MCI) diagnosis has entered the clinics' daily routine. However, there exist epistemic uncertainty and moral concerns whether early detection and prediction of dementia is clinically meaningful for the people affected, primarily due to the lack of effective treatment options. Methods: In this study, we adopted qualitative research methods. Twelve face-to-face interviews with tested persons with MCI and early dementia and five focus groups with family caregivers were conducted in Germany in order to explore and analyze their understanding and assessments of early detection and prediction of dementia in memory clinics. Results: Our study revealed that there was much uncertainty among the participants diagnosed with MCI especially when compared to the participants with an early dementia diagnosis. Their uncertainty concerned the meaning of a 'MCI' diagnosis as well as the validity of specific biomarker test results. Moreover, we identified different lines of moral issues for and against the tests among the participants. They include a) inter-familiar conflicts of interest in the initial phase of memory problems, b) the hope for (future) therapy and prevention, c) the desire for easier access to experts in memory clinics, d) advance planning, e) stigmatization, as well as, f) suicide as an option to avoid the future loss of self-determination. Conclusions: Current clinical and communication strategies only partly address the perspectives and needs of the affected. A standardized and ethically reflected procedure of the information provided by professionals before testing and afterwards, during disclosure, seems necessary. Further, longitudinal studies are needed to improve our knowledge about the experiences tested persons and family caregivers have with different levels of stigma. [ABSTRACT FROM AUTHOR]

Background: Today, a growing number of individuals with mild cognitive impairment (MCI) wish to assess their risk of developing Alzheimer's disease (AD) dementia. The expectations as well as the effects on quality of life (QoL) in MCI patients and their close others through biomarker-based dementia risk estimation are not well studied.Objective: The PreDADQoL project aims at providing empirical data on effects of such prediction on QoL and at developing an ethical and legal framework of biomarker-based dementia risk estimation in MCI.Methods: In the empirical study, 100 MCI-patients and their close others will be recruited from two sites (Germany and Spain). They receive standardized counselling on cerebrospinal fluid (CSF) biomarker-based prediction of AD dementia and a risk disclosure based on their AD biomarker status. A mixed methods approach will be applied to assess outcomes.Results: The pilot-study yielded a specification of the research topics and newly developed questionnaires for the main assessment. Within this binational quantitative and qualitative study, data on attitudes and expectations toward AD risk prediction, QoL, risk communication, coping strategies, mental health, lifestyle changes, and healthcare resource utilization will be obtained. Together with the normative part of the project, an empirically informed ethical and legal framework for biomarker-based dementia risk estimation will be developed.Conclusion: The empirical research of the PreDADQoL study together with the ethical and legal considerations and implications will help to improve the process of counselling and risk disclosure and thereby positively affect QoL and health of MCI-patients and their close others in the context of biomarker-based dementia risk estimation. [ABSTRACT FROM AUTHOR]

Background: Dementia is an age-related syndrome that is estimated to affect 46.8 million people worldwide (2015). In ageing populations, the prevalence of dementia is expected to increase. General practitioners (GPs) are often the first to be contacted when signs of dementia appear. This cluster-randomised trial (CRT) investigates the effects of a dementia care toolbox mailed to GP practices to facilitate dementia care. It contained patient brochures and posters for the waiting room in three languages, information cards for professionals and practical tools in three languages. The GPs' and practice assistants' (PrAs) use of and opinion about the toolbox is reported here. Methods: Three months after receiving the toolbox, participating GPs and PrAs were sent a standardised, self-administered questionnaire asking about the use and helpfulness of the various toolbox items by mail. Results: A total of 50 GPs and PrAs (14 GPs and 36 PrAs) from 15 practices completed the questionnaire. Of the participants, 82.0% reported using at least one of the tools, while 18.0% had used none. In descending order, the patient brochures (70.0%), the information card (58.0%) and the poster (40.0%) were used. In general, the brochures (52.1%), the information card (44.9%) as well as the poster (28.6%) were perceived as helpful. Conclusion: Overall, the dementia toolbox was widely accepted by both professional groups. Future research should investigate long-term effects of information strategies for GP practice settings. Trial registration: German Clinical Trials Register, DRKS00014632. Registered 02 August 2018. Clinical register of the study coordination office of the University hospital of Bonn. Registered 05 September 2017. [ABSTRACT FROM AUTHOR]

Background: The National Institute of Aging and Alzheimer's Association's diagnostic recommendations for preclinical Alzheimer's disease (AD) and mild cognitive impairment (MCI) define AD by pathological processes which can be detected by biomarkers. These criteria were established as part of a research framework intended for research purposes but progressively enter the clinical practice.Objective: We investigated the availability, frequency of use, interpretation, and therapeutic implications of biomarkers for the etiologic diagnosis and prognosis in MCI and subjective cognitive decline (SCD) in routine clinical care.Methods: We conducted a cross-sectional questionnaire survey among 215 expert dementia centers (hospitals and memory clinics) in Germany.Results: From the 98 centers (45.6% of contacted centers) included, two-thirds reported use of the cerebrospinal fluid (CSF) biomarkers Aβ42, tau, and phospho-tau in the diagnostic workup of MCI and one third in SCD. CSF biomarker analysis was more often employed by neurological (MCI 84%; SCD 42%) compared to psychiatric institutions (MCI 61%; SCD 33%; p≤0.001). Although dementia experts disagreed on the risk of progression associated with different CSF biomarker constellations, CSF biomarker results guided therapeutic decisions: ∼40% of responders reported to initiate cholinesterase inhibitor therapy in MCI and 18% in SCD (p = 0.006), given that all CSF biomarkers were in the pathological range.Conclusion: Considering the vast heterogeneity among dementia expert centers in use of CSF biomarker analysis, interpretation of results, and therapeutic consequences, a standardization of biomarker-based diagnosis practice in pre-dementia stages is needed. [ABSTRACT FROM AUTHOR]

Background: Autoimmune encephalitis is a new spectrum of autoimmune disorders of the central nervous system (CNS), which are characterized by pathogenic autoantibodies against neuronal surface antigens. Clinical presentations range from acute to subacute encephalopathy with neurological and psychiatric symptoms, and life-threatening autonomic dysfunction in severe cases. There exist no approved therapies nor is data available from controlled clinical trials. Patients are usually treated with diverse combinations of immunotherapy. However, effect of immunotherapy on antibody-producing cells and thus on levels of pathogenic autoantibodies is insufficient. Therefore, therapeutic response is sometimes prolonged with necessity of long-time intensive care treatment and also irreversible deficits occur in severe cases. This trial will investigate the efficacy and safety of bortezomib, a proteasome inhibitor known to selectively deplete plasma cells, in patients with severe autoimmune encephalitis who have been treated with rituximab with insufficient response.Methods: Generate-Boost is an investigator-initiated, multicenter, double-blinded, randomized controlled phase II trial which will be conducted in specialized neurological hospitals within the GENERATE (GErman NEtwork for Research on AuToimmune Encephalitis) network in Germany. Adult patients with severe autoimmune encephalitis (modified Rankin scale, mRS ≥ 3), autoantibodies against neuronal surface antigens, and pretreatment with rituximab are eligible for study participation. Fifty patients will be randomized 1:1 and undergo up to 3 cycles (each 21 days with 4 s. c. applications) of bortezomib or placebo. All patients will receive concomitant medication with dexamethasone, acyclovir and co-trimoxazole. The primary efficacy endpoint is the mRS score 17 weeks after first treatment application. Secondary endpoints are neurocognitive function, antibody titers, markers of neuronal cell damage, length of ICU/hospital stay, and mRS and Glasgow coma scale scores throughout the trial up to week 17. General and bortezomib-specific adverse events are monitored continuously.Discussion: The expected outcome of the study is to obtain first reliable data on a hypothesis-driven therapeutic option in severe and difficult-to-treat autoimmune encephalitis. If treatment with bortezomib is beneficial in these cases, this will be the basis for implementation in the current guidelines.Trial Registration: Clinicaltrials.gov , NCT03993262 . Registered June 20, 2019; German Clinical Trials Register, DRKS00017497. [ABSTRACT FROM AUTHOR]

Background: Current guidelines support the use of nuclear medical imaging (NMI) techniques for differential diagnostics of certain cases of dementia. Aims: We aimed at studying the association between using NMI and the accuracy of dementia diagnoses. Additionally, we evaluated the effect of conducting NMI on the duration of hospital treatment. Methods: This study was based on data collected according to §21 of the German hospital remuneration law, including relevant diagnostic and procedural codes for NMI in dementia patients. In total, more than 7.2 million cases treated in German psychiatric and somatic hospitals between 2015 and 2017 were included. Associations between the frequency of NMI and the accuracy of dementia diagnoses in terms of specific vs. unspecific diagnostic codes were analyzed using Fischer's exact test. Results: In total, 351,106 cases with a dementia diagnosis were encoded during the study period. NMI was performed in 1.03% or 0.15% of all patients with dementia in psychiatric or somatic clinics, respectively. In psychiatric clinics, the proportion of unspecific dementia diagnoses decreased from 20.86% in 2015 to 17.73% in 2017. NMI was mainly performed within psychiatric day-care settings. Interestingly, patients receiving NMI stayed shorter within day-care settings (8.1 ± 16.0 days) compared to inpatient settings (38.3 ± 44.7 days). Conclusions: Nuclear medical imaging is often performed in psychiatric day-care settings. Further studies are warranted to understand the predictive diagnostic value of NMI in dementia diagnosis compared with clinical, CSF and structural imaging in different healthcare settings. [ABSTRACT FROM AUTHOR]

As the population of the world gets older, cognitive and mental health decline in older adults has become one of the most pressing scientific problems of the 21st century. It has been well-established that multiple pathways exist that can lead to future cognitive decline and the development of age-related mental health conditions. Making matters more complicated is the fact that aging is not a homogenous or simple process; rather, each person brings a diverse set of circumstances to the table, leading to differences in biologically aging. Research is needed to identify how the intersection of environmental and biological factors may protect older adults or put them at future risk for cognitive decline and the development of age-related mental health conditions. Furthermore, each potential factor may impact different domains of cognition and mental health or may impact individuals differentially based on genetic, environmental, social, emotional, and behavioral factors. Neuroimaging is one key tool that can be used to discover and assess markers of cognitive and mental health. The goal of this special issue is to expand the science on how biological markers can aid the understanding of aging and mental health through the lens of the individual from an international perspective, representing Germany, Taiwan, Thailand, the United Kingdom, and the United States. Common themes from these articles are used to support the new Seed and Soil Model of Neurocognitive Disorders. [ABSTRACT FROM AUTHOR]

Dementia is associated with the gradual impairment of mental ability. The population of people suffering from dementia is as large as 50 million. Most dementia cases result from various neurodegenerative diseases (NDs) linked by a progressive degeneration of neurons. Among NDs, Alzheimer's disease (AD) is the most frequent cause of dementia and accounts for 60- 80% of cases. Certain pathological changes on the cellular and subcellular level occur even 15 years before the manifestation of clinical symptoms of AD. This first asymptomatic phase of AD is considered a preclinical stage, whereas mild cognitive impairment (MCI) is the symptomatic pre-dementia stage. The third, fully symptomatic phase of AD is dementia due to AD. The presence of specific proteins in the cerebrospinal fluid (CSF) may be considered as a characteristic feature of some NDs. The measurement of their CSF concentrations, together with neuropsychological examination and neuroimaging, may be useful for diagnosing AD. The collection of CSF samples is performed by lumbar puncture, which is a medical procedure that requires obtaining informed consent from patients. While asymptomatic AD patients have full legal capacity, those with dementia require a legal guardian who will represent them. Thus, the objective of this study is to compare the legal systems regulating the legal capacity issue in the USA, U.K. (England and Wales), Germany, and Poland. These countries have been chosen as examples of three different types of legal orders, according to the sources of law, i.e., civil law, common law, and case law. [ABSTRACT FROM AUTHOR]

Little is known about the diagnostic methods currently used in routine care for patients with mild cognitive impairment (PwMCI). We estimated the frequency of diagnostic procedures in incident PwMCI compared to incident patients with dementia (PwD) in 2016-2017. The study is based on the Disease Analyzer database. After matching by age and sex, 4,700 PwMCI and 4,700 PwD were available. The diagnostic procedures were identified on the basis of the related medical fee schedule items. All diagnostic procedures were used more frequently in PwMCI than in PwD. The drafting of a practice-oriented MCI guideline is an important task for the future. [ABSTRACT FROM AUTHOR]

Background: The diagnosis of mild cognitive impairment (MCI) is becoming increasingly important for the medical treatment of dementia.Objective: The aim of this study was to investigate whether the coded prevalence of MCI changed in the period from 2007 to 2017 compared to dementia diagnoses.Methods: This was a retrospective evaluation of diagnostic data from 432 general practitioner (GP) practices and 53 neuropsychiatrist (NP) practices in Germany based on the Disease Analyzer database (IQVIA). The frequencies with which MCI and dementia were diagnosed in these practices were determined. The frequency with which dementia was diagnosed was included to determine whether the change in the frequency of MCI diagnoses was due to the increase in dementia prevalence.Results: It was found that the number of GP practices with patients receiving MCI diagnoses increased from 16% to 46%, while the number of NP practices with patients receiving MCI diagnoses increased from 55% to 75%. Moreover, the study found an increase in the coded prevalence of MCI from 0.4 to 1.9 patients/GP practice and from 6.5 to 11.1 patients/NP practice were observed.Conclusions: A growing number of GPs and NPs code MCI with increasing frequency. However, the coding frequency of MCI in 2017 corresponded to less than 10% of its true prevalence. A sharp increase in MCI diagnoses can be expected, along with the establishment of preventive and disease-modifying dementia strategies. [ABSTRACT FROM AUTHOR]

Background: Biomarker-supported testing for preclinical and prodromal Alzheimer's disease (AD) finds its way into clinical practice. Professional attitudes and practices regarding disclosure and ethical issues are controversial in many countries.Objectives: Against this background, the objective was to survey the actual practice and the attitudes of physicians in German hospitals and memory clinics in order to explore possible practical insecurities and ethical concerns.Methods: A detailed survey with 37 items was conducted among medical professionals at German hospitals and memory clinics (n = 108). Analyses were performed using SPSS 21.0 (IBM). Findings were based on frequency and percentage distribution.Results: Nearly half of the respondents stated that persons with mild cognitive impairment and pathological cerebrospinal fluid biomarkers were informed they had or would soon develop AD. While 81% acknowledged a 'right not to know', 75% said that results were always communicated. A majority agreed there was a benefit of prediction or later life planning [end-of-life, financial, family, housing (73-75%)] but also expected high psychological stress (82%) and self-stigmatization (70%) for those tested.Conclusions: There is considerable heterogeneity and insecurity regarding prediction and early detection in the context of AD in Germany. Information of professionals and standardization of professional testing and disclosure practices are needed. [ABSTRACT FROM AUTHOR]

Background: In the future, an increase in health care needs in the elderly is expected. Reports on unmet care needs of the oldest old with cognitive disorders are pending. This study aims at exploring unmet needs in the oldest old primary care patients with mild cognitive impairment (MCI) and dementia. Furthermore, the association between sociodemographic and clinical factors and unmet needs ought to be analyzed. Methods: Based on the study "Needs, Health Service Use, Costs and Health-Related Quality of Life in a Large Sample of Oldest-Old Primary Care Patients (85+)" (AgeQualiDe), 749 patients (unimpaired, MCI, and dementia) aged 85 years and older, their relatives (n = 421), and general practitioners (GPs) (n = 607) were assessed. Descriptive, inferential, and regression analyses were run. Results: Most unmet needs were observed in dementia patients, although needs were less frequently rated as unmet by dementia patients themselves as compared to relatives and GPs. Unmet needs were associated with MCI and dementia; other risk factors were age, education, and marital status. Conclusion: This study provides first data on unmet needs according to different perceptions in the elderly with MCI and dementia in Germany. Need assessments should be part of medical examinations to ensure a high-quality health care in the elderly. [ABSTRACT FROM AUTHOR]

There is increasing evidence that anemia is associated with cognitive impairment. Therefore, the aim of the study was to examine the cross-sectional association of anemia as well as the persistence of anemia over the last five years with mild cognitive impairment (MCI) and MCI subtypes (amnestic/non-amnestic MCI (aMCI/naMCI)). Out of 4,157 participants (50% men, 50-80 years) of the second examination (t1) of a cohort study (baseline (t0) 2000-2003), we included 4,033 participants with available hemoglobin information and complete cognitive assessment. Anemia was defined as hemoglobin <13 g/dl in men (n = 84) and <12 g/dl in women (n = 79). Group comparisons were used to compare the cognitive subtests. To determine the association of MCI with anemia at t1, with anemia five years prior to the cognitive assessment (t0) and anemia at both time points, we used logistic regression models and included 579 participants with MCI and 1,438 cognitively normal participants out of the total cohort. Anemic participants showed lower performances in verbal memory and executive functions. The fully adjusted odds ratios (OR) for MCI, aMCI, and naMCI in anemic versus non-anemic participants were 1.92 (95% -CI, 1.09-3.39), 1.96 (1.00-3.87), and 1.88 (0.91-3.87). Anemia at both times points showed a non-significant association with naMCI (OR 3.74, 0.94-14.81, fully adjusted). Our results suggest that anemia is associated with an increased risk of MCI independent of traditional cardiovascular risk factors. The association of anemia and MCI has important clinical relevance, because many causes of anemia can be treated effectively. [ABSTRACT FROM AUTHOR]

Routinely collected booking records of salvaged timber from the period 1979-2008 were used to empirically model the (1) storm damage probability; (2) proportions of storm-damaged timber and (3) endemic storm damage risk in the forest area of the German federal state of Baden-Wuerttemberg by applying random forests. Results from cross-validated predictor importance evaluation demonstrate that the relative impact of modeled gust speed fields on the predictive accuracy of the random forests models was greatest compared to the impact of forest and soil features. Forest areas prone to storm damage occurring within a period of five years were mainly located in mountainous upland regions where maximum gust speed exceeds 31 m/s in a five-year return period and conifers dominate the tree species composition. While mean storm damage probability continuously increased with increasing statistical gust speed proportions of storm-damaged timber peaked at a statistical maximum gust speed value of 29 m/s occurring in a five-year return period. Combining the statistical gust speed field with daily gust speed fields of two exceptional winter storms improved model accuracy and considerably increased the explained variance. Endemic storm damage risk was calculated from endemic storm damage probability and proportions of endemically storm-damaged timber. In combination with knowledge of local experts the storm damage risk modeled in a 50 m × 50 m resolution raster dataset can easily be used to identify areas prone to storm damage and to adapt silvicultural management regimes to make forests more windfirm. [ABSTRACT FROM AUTHOR]

Objective: Preclinical evidence suggests a role for brain-derived neurotrophic factor (BDNF) in the mode of action of electroconvulsive therapy (ECT). Clinical data regarding BDNF levels in serum or plasma are more inconsistent. We measured BDNF levels from the cerebrospinal fluid (CSF) in patients with major depression before and shortly after a course of ECT., Methods: Cerebrospinal fluid and serum BDNF levels were determined using commercially available enzyme-linked immunosorbent assay (ELISA) kits., Results: We included 9 patients with a severe depressive episode within a major depressive disorder into the study. The CSF BDNF concentrations at baseline were lower compared with those CSF BDNF levels after the complete ECT treatment (P = 0.042), whereas no such a constellation was found for serum BDNF. No associations between the BDNF levels and the amount of individual ECT sessions or the reduction of the depressive symptoms were found., Conclusions: For the first time, it has been shown that CSF BDNF concentrations increase during a course of ECT in patients with a severe unipolar depressive episode, which is in line with the neurotrophin hypothesis as a mode of action of ECT, although it was not possible to demonstrate either a dose-effect relation or a relationship with the actual antidepressant effects in our small sample. Major limitation is the small sample size.

Background: Analysis of cerebrospinal fluid (CSF) has improved over the last few years; thus specific markers for different diseases have emerged, e.g., amyloid-β (Aβ) for Alzheimer's disease (AD) and progranulin for frontotemporal dementia (FTD).Objective: Evaluation of correlation between biomarkers in CSF and cognitive performance in populations with AD and FTD.Methods: 27 patients with AD and 16 with FTD were included. CSF tau, P-tau(181P), Aβ₄₂, and progranulin (PGRN) were measured and a standardized neuropsychological test battery applied. Olfactory testing was additionally included where available.Results: For all patients across both groups, an association between PGRN and categoric (p = 0.016) and letter fluency (p = 0.029), naming (p = 0.003), and overall cognition (Mini-Mental State Examination: p = 0.04) was observed. Aβ42 was strongly associated with memory function (learning: p = 0.001; recall: p = 0.002). A correlation between Aβ₄₂ and memory performance was moreover found for each group separately, while PGRN also showed a correlation with recognition memory (p = 0.04) in AD. Furthermore, an association between reduced PGRN and olfactory dysfunction was revealed (p = 0.01).Conclusions: CSF-levels of PGRN and Aβ₄₂ levels express deficits in cognition differentially, with PGRN being predominantly associated with frontal and Aβ₄₂ with temporal dysfunction. This mirrors the cerebral occurrence of these proteins. These associations appear to be consistent across both disease groups. The relationship between PGRN and olfaction further underpins the association between PRGN and frontal dysfunction. [ABSTRACT FROM AUTHOR]

Forestry professionals' perceptions of the risks and uncertainties associated with climate change were investigated in a questionnaire survey in south-west Germany. The respondents were employed in forestry in either public or private forests or working for state authorities. They were specifically asked about the related impacts of climate change on forest ecosystems, adaptive forest management and the potential of forestry to mitigate climate change. A factor analysis of the responses revealed significant variables explaining the major part of the variance and the key variable groups were identified in a canonical analysis. The majority of respondents (72 %) said they were under-informed, but most (83 %) view climate change as a reality, human-caused, and a significant risk. These forestry professionals were particularly concerned about extreme hazards, water scarcity, and changes in climatic zones. They generally said the potential of forestry to mitigate climate change is low, and saw few realistic measures like increased harvesting to substitute fossil fuels and energy-intensive materials for mitigation. Despite the uncertainty involved, adaptation strategies like using better-adapted tree species and provenances were mainly perceived as helpful, and tools such as spatially-explicit maps with recommendations for adapted species and indices of biotic and abiotic risks as important. The forestry professionals reported obtaining their information about climate change from advanced forestry training, the media, and scientific literature. The findings of the study are discussed in the light of the ongoing debate on climate change in Germany and recommendations made, including periodically checking and improving forestry professionals' knowledge about climate change. [ABSTRACT FROM AUTHOR]

Background: The cytokine tumor necrosis factor-alpha (TNF-α) is elevated in the blood of Alzheimer's disease (AD) patients. Epigenetic DNA modifications of the TNF-α promoter may account for the observed upregulation. Methods: We analyzed blood samples of 50 AD patients and 55 controls plus 4 AD and 4 control cortex samples using bisulfite sequencing PCR. Results: A significant hypomethylation of the TNF-α promoter was found in AD patients' brains but not in their blood. Cortical TNF-α promoter DNA was higher methylated than blood-derived DNA, both in AD patients and controls. Conclusion: In AD patients, epigenetic mechanisms of TNF-α gene regulation, like aberrant DNA methylation, are not relevant in blood. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background/Aims: There is an increasing interest in using the Montreal Cognitive Assessment (MoCA) test as a monitoring tool in Alzheimer's disease (AD) in both research and clinical settings. Our aim was to investigate the utility of alternate forms of the MoCA in detecting cognitive deterioration in a sample of early AD patients followed longitudinally in an outpatient memory clinic. Method: Twenty-five patients with early-stage AD (prodromal or mild dementia) were administered the original version and one of two previously validated alternate forms of the MoCA within an interval of about 1 year. The decline over time and the rate of change of the MoCA were compared to the total score of a standardized neuropsychological assessment battery (Consortium to Establish a Registry of Alzheimer's Disease; CERAD-Plus). Responsiveness to change was determined by calculating standard response means and the respective effect sizes. Results: Sixty percent of the sample showed a clinical decline on the clinical dementia rating (CDR) scale. There was significant deterioration in the MoCA and CERAD total scores. Conclusion: The results demonstrate that the MoCA is capable of detecting change over time and seems to be a valid tool with small to moderate sensitivity for monitoring cognitive change in early AD. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The anticipatory proportion (AP), the ratio between perseverative and anticipatory speech errors, is reduced in patients with brain injury. However, it is unknown whether the AP is also reduced in elderly speakers with cognitive impairment. Methods: 20 elderly speakers with a Mini Mental State Examination (MMSE) score of 25-27 and 20 elderly speakers with an MMSE score of 28-30 were assessed using a tongue-twister-based speech test, the Regensburg Word Fluency Test (RWT) and an object naming test. Results: The AP in the group of speakers with an MMSE score of 25-27 was significantly lower. Accordingly, the AP and scores in the RWT and the object naming test were higher in persons with an MMSE score of 28-30. Conclusion: Language alterations in mild cognitive dysfunction are detectable with the AP. Further longitudinal studies are needed to evaluate the predictive value of the AP. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Primary objectives: The primary aim was to investigate the impact of neuron-specific enolase (NSE) and S100 calcium-binding protein B (S100b) on cognitive functioning after cardiopulmonary bypass (CPB). Research design: Prospective exploratory study. Setting: Psychiatric Consultation-Liaison Service, Ludwig-Maximilians-University Medical School, Munich, Germany. Participants: Thirty-four patients who underwent elective CPB. Measurements: Before the CPB and on the day before discharge neurocognitive tests based on the Syndrom Kurztest (SKT) were carried out. During the ICU stay and shortly after discharge from the ICU, the delirious state was evaluated daily using the Delirium-Rating-Scale. NSE and S100b levels were assayed before CPB, 24 hours and 48 hours post-operatively and on the day before discharge. Results: After the CPB, 1 day before discharge, six (17.6%) participants had sub-threshold cognitive deficits and seven (20.6%) had clinically significant cognitive deficits. A trend toward persistently high NSE levels at discharge indicates greater cognitive impairment at the time of discharge. After surgical intervention S100b is elevated in all patients, independent of cognitive status. Conclusions: Persistently high levels of NSE might be a useful biomarker to identify patients with cognitive performance impairments, while no significant correlation between levels of S100b and impaired cognitive function were found. [ABSTRACT FROM AUTHOR]

Background/Aim: To investigate the influence of established genetic risk factors for Alzheimer's disease on the speed of disease progression. Methods: Polymorphisms (in ACE, ApoE, BIN1, CLU, CR1, CST3, EXOC3L2, GWA14q32.13, IL8, LDLR, PICALM, TNK1) of 40 Alzheimer's disease patients from a longitudinal study were analyzed. A standardized loss of Mini-Mental State Examination points was used as the progression parameter. Results: Polymorphisms in CST3 and EXOC3L2 as well as the absence of APOE4 were associated with more aggressive disease courses. A trend was observed for BIN1. Conclusion: In addition to being a risk factor for disease development, some of the polymorphisms investigated here are associated with higher rates of decline and disease progression and thus might act as prognostic disease markers. This effect needs to be considered in future treatment strategies. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Storms represent the most important disturbance factor in forests of Central Europe. Using data from long-term growth and yield experiments in Baden-Wuerttemberg (south-western Germany), which permit separation of storm damage from other causes of mortality for individual trees, we investigated the influence of soil, site, forest stand, and tree parameters on storm damage, especially focusing on the influence of silvicultural interventions. For this purpose, a four-step modeling approach was applied in order to extract the main risk factors for (1) the general stand-level occurrence of storm damage, (2) the occurrence of total stand damage, and (3) partial storm damage within stands. The estimated stand-level probability of storm damage obtained in step 3 was then offset in order to describe the damage potential for the individual trees within each partially damaged stand (4). Generalized linear mixed models were applied. Our results indicate that tree species and stand height are the most important storm risk factors, also for characterizing the long-term storm risk. Additionally, data on past timber removals and selective thinnings appear more important for explaining storm damage predisposition than for example stand density, soil and site conditions or topographic variables. When quantified with a weighting method (summarizing the relative weight of single predictors or groups of predictors), removals could explain up to 20% of storm risk. The stepwise modeling approach proved an important methodological feature of the analysis, since it enabled consideration of the large number of observations without damage ('zero inflation') in a statistically correct way. These results form a reliable basis for quantifying forest management's direct impact on the risk of storm damage. [ABSTRACT FROM AUTHOR]

Aims: The study of cognitive functioning in large epidemiological settings is hampered by a lack of instruments for the remote assessment of cognitive performance, especially when targeting variability across the full range of adult functioning. The present study examined the practicability of such investigations using a recently developed telephone interview (Cognitive Telephone Screening Instrument, COGTEL). Methods: A subcohort of an ongoing epidemiological study in the elderly German population (ESTHER) was interviewed via telephone by trained personnel. These data were combined with sociodemographic information obtained by standardized self-administered questionnaires, and analysed by tabulation, histograms and regression models. Results: A total of 1,697 interviews could be analysed. The eligible participants had a mean age ± standard deviation of 74.0 ± 2.8 years. The COGTEL total scores closely followed a normal distribution with no evidence of a ceiling effect. In adjusted regression models, COGTEL total and subcomponent scores were negatively associated with age and strongly positively with higher education, whereas the association with sex was less consistent. Conclusions: The results suggest that the COGTEL can readily be administered to large study populations and produces plausible and informative results. Education should be considered in all investigations using this instrument and requires further in-depth analyses. Future studies will need to elucidate its associations with risk factors and its prognostic potential for cognitive decline and dementia. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Aims: We investigated the prevalence of mild cognitive impairment (MCI) and its subtypes according to the original (MCI-original) and modified (MCI-modified; neglecting cognitive complaints) Petersen criteria. Methods: 4,145 subjects (aged 50-80 years) from a German population-based study completed a cognitive screening test and were poststratified into 2 groups with sample sizes of 1,125 for impaired and 3,020 for age-appropriate performance. Random samples of 445 impaired participants and 211 age-appropriate participants received a detailed neuropsychological evaluation. The prevalence of MCI was estimated by a bias correction estimator based on stratum weights. The association between MCI and age, gender and education was analyzed in a logistic regression model. Results: The estimated MCI prevalence was 7.8% (95% CI: 5.7-9.9%) for the original, and 12.1% (95% CI: 9.8-14.4%) for the modified criteria. In the MCI-original group, amnestic MCI subtypes were slightly less common than non-amnestic MCI subtypes (3.5 vs. 4.3%). MCI-original was associated with lower education and older age. In the MCI-modified group, the amnestic subtypes were more common than the non-amnestic MCI subtypes (7.8 vs. 4.3%), and MCI was associated with age, gender and education. Conclusions: Prevalence rates of MCI are high in the general population and vary considerably according to the criteria applied. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

"clinical NEUroPROteomics of neurodegenerative diseases" (cNEUPRO) is a Specific Targeted Research Project (STREP) within the sixth framework program of the European Commission dedicated to the search for novel biomarker candidates for Alzheimer's disease and other neurodegenerative diseases. The ultimate goal of cNEUPRO is to identify one or more valid biomarker(s) in blood and CSF applicable to support the early and differential diagnosis of dementia disorders. The consortium covers all steps required for the discovery of novel biomarker candidates such as acquisition of high quality CSF and blood samples from relevant patient groups and controls, analysis of body fluids by various methods, and finally assay development and assay validation. Here we report the standardized procedures for diagnosis and preanalytical sample-handling within the project, as well as the status of the ongoing research activities and some first results. [ABSTRACT FROM AUTHOR]

Working in the forest is dangerous, especially in the case of motor manual work, which represents a significant proportion of all forest work in Germany. Nevertheless, many accidents in the forest also happen during recreational activities. In the unfortunate case of an accident, rapid assistance is therefore crucial. For provision of this service, a network of 63,718 high quality permanent rescue points has been established in Germany, known to all persons involved in rescue operations. These can serve as meeting points and points of orientation. The question emerges whether the number of points is sufficient and whether they are well distributed and ideally placed for conducting a rescue in the forest. Therefore, this study aims to provide a granular complex geographic analysis of the indices of distribution and the accessibility of existing rescue points. These analyses form the basis for improving and optimising the existing permanent rescue point system at federal states and the federal level. This study has developed, calculated, analysed, and assessed nine different spatial indices, which can serve as a basis for decision making in the evaluation and adaptation of the system. The indices reveal considerable federal states differences in the designation of rescue points, in terms of number, density, and distribution. [ABSTRACT FROM AUTHOR]