Search

• Mineral liners from pre-treated dredged material may fail in distinct phases. • A mineral liner from pre-treated dredged material performed well for 20 years. • The design of the entire cover system is important for the liner performance. • A "slow" lateral drainage layer keeps the liner surface moist. • Hydro-chemical data are helpful for identifying hydrologic processes. The water balance and effectiveness of a landfill cover containing a liner from fine-grained dredged material ('METHA-material') and a drainage layer from sandy dredged material ('METHA-sand') from the Port of Hamburg (Northern Germany) was investigated for 20 years using two test fields (lysimeters), each 500 m2 in size. The layering within the standard design test field (FS) is identical to the layering of the cover on the landfill, whereas the alternative design test field (FA) was designed to provoke desiccation of the liner. The setup abstained from continuous side walls cutting through the liners in order to allow for material properties representative for the landfill cover, at the cost of possible minor lateral inflows or outflows, which were, however, considered negligible. By example of the lysimeter FA the risk of desiccation-induced failure of a liner from METHA-material under the given climate could be shown. In contrast, the discharges and hydro-chemical parameters measured for the lysimeter FS indicate continuous high efficiency of the liner until today. The average discharge below the liner was 14.9 mm/yr. The entire cover contributes to the good liner performance. Reason are (1) the low hydraulic conductivity of the liner (5 × 10−10 m/s) and its large thickness (1.5 m); (2) the increased stresses on the liner due to the 2.5 m thick overlaying cover; (3) the 1.0 m thick drainage layer from slowly-draining METHA-sand, allowing for a continuous nearly water-saturated fringe above the liner; and (4) the sufficient amount of plant available water in the recultivation layer. [ABSTRACT FROM AUTHOR]

Various measures are used to improve the quality of stroke care. In Germany, these include concentrating treatment in specialized facilities (stroke units), mandatory quality comparisons of hospitals in some German states, and treatment according to prespecified structure and process specifications (neurological complex treatment 8-981 or 8-98b). These measures have previously only been analyzed individually and regarding short-term patient outcomes. This study analyzes these measures in combination, considering patients' comorbidities as well as stroke severity in a longitudinal perspective. Analyses were based on data from 243,415 insurees of Germany's biggest health insurance (AOK) admitted to hospitals between 2007 and 2017 with cerebral infarction. Mortality risk was calculated using Cox regressions adjusted for various covariates. Kaplan-Meier analyses were differentiated by treatment site (stroke unit/external quality assurance/ Federal State Consortium of Quality Assurance Hesse – LAGQH) were performed, followed by log-rank tests and p-value adjustment. Trend analyses were performed for treatment types in combination with treatment sites. All analyses showed significant advantages for patients who received Neurological Complex Treatment, especially when the treatment was performed under external quality assurance conditions and/or in stroke units. There was an increasing frequency of specialized stroke treatment. Quality-enhancing structures and processes are associated with a lower mortality risk after stroke. There appears to be evidence of a cascading benefit from the implementation of neurological complex treatment, external quality assurance, and ultimately, stroke units. Consecutively, care should be concentrated in hospitals that meet these specifications. However, since measures are often applied in combination, it remains unclear which specific measures are crucial for patient outcome. [ABSTRACT FROM AUTHOR]

Unlabelled: Patients with depression often report pain. Evidence regarding altered pain sensitivity in depressed patients remains, however, inconclusive. In a large cross-sectional study we investigated the association between depression and pain sensitivity with regard to 2 different dimensions of pain sensitivity, as well as the effect of somatic cofactors, symptom severity, and subtype of depression. In 735 patients with a current episode of major depression and 456 never-depressed control participants pain thresholds (pressure pain thresholds, PPTs) were measured at the index finger pad and self-rated suprathreshold pain intensity ratings were obtained using the Pain Sensitivity Questionnaire (PSQ)-minor subscore, an instrument that assesses pain intensity in daily life situations. Additionally, lifestyle factors, medical, and psychiatric conditions were assessed. Unadjusted, patients with depression had lower PPTs and higher PSQ-minor scores indicating increased pain sensitivity. After adjusting for potential mediators, such as poor sleep quality and physical inactivity, patients did not differ from control participants regarding PPTs, but still had significantly higher PSQ-minor ratings. Among patients with depression, severity of anxiety symptoms predicted higher PSQ-minor scores. In conclusion, we found a differential effect of depression on the 2 pain sensitivity dimensions: Decreased experimentally obtained pain thresholds were explained by depression-associated somatic factors whereas increased self-rated suprathreshold pain intensity ratings were associated with increased anxiety symptoms.Perspective: Because increased pain intensity perception is hypothesized to be a risk factor for the development of chronic pain, our findings may contribute to understanding the high incidence of chronic pain in depressed patients. They also encourage clinicians to consider the role of anxiety in treatment programs for pain in patients with depression. [ABSTRACT FROM AUTHOR]

The Hydrologic Evaluation of Landfill Performance (HELP) model is the most widely applied model to calculate the water balance of cover and bottom liner systems for landfills. The paper summarizes the 30 year history of the model from HELP version 1 to HELP 3.95 D and includes references to the three current and simultaneously available versions (HELP 3.07, Visual HELP 2.2, and HELP 3.95 D). A sufficient validation is an essential precondition for the use of any model in planning. The paper summarizes validation approaches for HELP 3 focused on cover systems in the literature. Furthermore, measurement results are compared to simulation results of HELP 3.95 D for (1) a test field with a compacted clay liner in the final cover of the landfill Hamburg-Georgswerder from 1988 to 1995 and (2) a test field with a 2.3 m thick so-called water balance layer on the landfill Deetz near Berlin from 2004 to 2011. On the Georgswerder site actual evapotranspiration was well reproduced by HELP on the yearly average as well as in the seasonal course if precipitation data with 10% systematic measurement errors were used. However, the increase of liner leakage due to the deterioration of the clayey soil liner was not considered by the model. On the landfill Deetz HELP overestimated largely the percolation through the water balance layer resulting from an extremely wet summer due to an underestimation of the water storage in the layer and presumably also due to an underestimation of the actual evapotranspiration. Finally based on validation results and requests from the practice, plans for improving the model to a future version HELP 4 D are described. [ABSTRACT FROM AUTHOR]

Background: Few studies have investigated the impact of neighborhood characteristics on mortality after stroke. Aim of our study was to analyze the influence of district unemployment as indicator of neighborhood socioeconomic status (SES-NH) on poststroke mortality, and to compare these results with the mortality in the underlying general population. Methods: Our analyses involve 2 prospective cohort studies from the city of Dortmund, Germany. In the Dortmund Stroke Register (DOST), consecutive stroke patients (N = 1883) were recruited from acute care hospitals. In the Dortmund Health Study (DHS), a random general population sample was drawn (n = 2291; response rate 66.9%). Vital status was ascertained in the city's registration office and information on district unemployment was obtained from the city's statistical office. We performed multilevel survival analyses to examine the association between district unemployment and mortality. Results: The association between neighborhood unemployment and mortality was weak and not statistically significant in the stroke cohort. Only stroke patients exposed to the highest district unemployment (fourth quartile) had slightly higher mortality risks. In the general population sample, higher district unemployment was significantly associated with higher mortality following a social gradient. After adjustment for education, health-related behavior and morbidity was made the strength of this association decreased. Conclusions: The impact of SES-NH on mortality was different for stroke patients and the general population. Differences in the association between SES-NH and mortality may be partly explained by disease-related characteristics of the stroke cohort such as homogeneous lifestyles, similar morbidity profiles, medical factors, and old age. [Copyright &y& Elsevier]

Summary: Sleep is an essential human behavior that shows prominent gender differences. Disturbed sleep, in particular, is much more prevalent in females than males. Restless legs syndrome (RLS) as one cause of disturbed sleep was observed to be somewhat more common among women than men in Ekbom''s 1945 seminal series of clinical cases with the disease. He, however, reported this gender difference mainly for those with more severe symptoms. Since then numerous studies have reported that women are affected by RLS about twice as often as males for mild as well as moderate to severe RLS. The present review focuses on RLS in females from the perspectives of both epidemiology and pathophysiology. RLS will generally become worse or might appear for the first time during pregnancy. Parity increases the risk of RLS later in life suggesting that pregnancy is a specific behavioral risk factor for developing RLS. Some evidence suggests that dysfunction in iron metabolism and high estrogen levels might contribute to RLS during pregnancy. But, menopause does not lower the incidence of RLS nor does hormone replacement therapy lead to an increase, suggesting a quite complex uncertain role of hormones in the pathophysiology of RLS. Therefore, further, preferably longitudinal studies are needed to unravel the factors causing RLS in women. These studies should include genetic, clinical and polysomnographic variables, as well as hormonal measures and variables assessing iron metabolism. [Copyright &y& Elsevier]

Abstract: Several animal studies demonstrated that olfaction is modulated by dopamine (DA). We examined if such results could be replicated in humans. Thus, we tested olfaction in elderly healthy humans before and after external administration of levodopa in a double-blind, placebo-controlled, randomized cross-over study. Main outcome measure was the sum of correctly identified odors in an odor identification paradigm. In contrast to what had been demonstrated in rats, levodopa did not improve olfaction. We even noted a trend for the reverse. Blood pressure, mood ratings, as well as performance in a simple motor task were comparable between conditions, indicating that levodopa did not induce differences in general arousal, mood, attention, or reaction time. Our findings may be explained by differences in the distribution of dopaminergic receptor subtypes in the olfactory system in animals and humans, by relative differences in dosing regimes, or by subtle differences in the respective paradigms. These hypotheses have to be tested in future experiments, but our study demonstrates that results from animal studies cannot be directly transferred to the human situation. [Copyright &y& Elsevier]

Summary: Epidemiological studies in restless legs syndrome (RLS) have often been limited by misdiagnosis and by the fact that affected individuals, even when their symptoms are severe, might not seek medical care. Some of these limitations have been overcome in the last years as population studies based on face to face interviews have been carried out with new standardized diagnostic criteria. According to these studies, and in contrast to earlier views, RLS has been shown to be a common disorder with prevalences ranging between 2.5 and 10% of the population. Although few studies performed outside Europe/North America have shown a low prevalence, a number of methodological issues have been raised that might question these results. Furthermore, once established, RLS usually follows a chronic course, and preliminary evidence shows that it might worsen over time in some patients. Endstage renal disease, increasing age, female gender, pregnancy, frequent blood donations, iron deficiency and neuropathy are considered to be risk factors for this disorder. The association to RLS is less definitely established for other conditions, such as PD or diabetes. In summary, epidemiological evidence suggests that RLS is a common neurological disorder—with high impact on many aspects of the life of those affected. [Copyright &y& Elsevier]

Abstract: The aging, non-demented brain undergoes several physiological changes, some of which may affect cognitive function. The goal of the present study was to examine the associations between subcortical and periventricular white matter hyperintensities (WMHs), cortical and subcortical atrophy, and cognitive function (episodic memory, word fluency, attention, and perceptual, cognitive, and motor speed). This was done within a European collaborative study, Cardiovascular Determinants of Dementia (CASCADE), in which magnetic resonance imaging (MRI) was performed on community-dwelling individuals. The study includes 1254 persons from eight European study centers, ranging between 64 and 76 years of age (M 69.4±3.3; 55% men). When demographics (age, education, and sex), study center, and concurrent brain changes had been adjusted for, periventricular WMHS predicted lower performance in word fluency and the Stroop test (time), and subcortical atrophy predicted lower performance in motor speed and the Stroop test (errors). The findings are consistent with findings from lesion and functional neuroimaging studies. [Copyright &y& Elsevier]

Neuroimaging studies of suicidal behavior have so far been conducted in small samples, prone to biases and false-positive associations, yielding inconsistent results. The ENIGMA-MDD Working Group aims to address the issues of poor replicability and comparability by coordinating harmonized analyses across neuroimaging studies of major depressive disorder and related phenotypes, including suicidal behavior. Here, we pooled data from 18 international cohorts with neuroimaging and clinical measurements in 18,925 participants (12,477 healthy control subjects and 6448 people with depression, of whom 694 had attempted suicide). We compared regional cortical thickness and surface area and measures of subcortical, lateral ventricular, and intracranial volumes between suicide attempters, clinical control subjects (nonattempters with depression), and healthy control subjects. We identified 25 regions of interest with statistically significant (false discovery rate <.05) differences between groups. Post hoc examinations identified neuroimaging markers associated with suicide attempt including smaller volumes of the left and right thalamus and the right pallidum and lower surface area of the left inferior parietal lobe. This study addresses the lack of replicability and consistency in several previously published neuroimaging studies of suicide attempt and further demonstrates the need for well-powered samples and collaborative efforts. Our results highlight the potential involvement of the thalamus, a structure viewed historically as a passive gateway in the brain, and the pallidum, a region linked to reward response and positive affect. Future functional and connectivity studies of suicidal behaviors may focus on understanding how these regions relate to the neurobiological mechanisms of suicide attempt risk. [ABSTRACT FROM AUTHOR]

Objective: We examined (i) the mean-level stability and change of trait resilience with age in three cohorts from a single study (population-based controls, depression patients, cardiovascular disease (CVD) patients), (ii) associations of sociodemographic, personality, and other factors (sex, education, Big Five, childhood trauma, depressive symptoms) with trait resilience, and (iii) the intra-individual stability across repeated trait resilience self-assessments.Methods: 1544 participants from the BiDirect Study completed the Resilienzskala-11 (RS-11; German short version of the resilience scale 25) up to three times over about four years. The repeated-measures data were analyzed using linear mixed models, stratified by cohort. Outcome was the RS-11 score, the underlying time variable was age. All factors mentioned above were considered as fixed main effects. Bland-Altman plots assessed intra-individual stability of RS-11 scores.Results: (i) In the population-based control cohort, there was no association between age and trait resilience (est.: -0.01; 95%-CI: -0.06, 0.04). There were modest positive associations in the patient cohorts (depression: est.: 0.08; 95%-CI: -0.01, 0.16; CVD: est.: 0.15; 95%-CI: 0.03, 0.26). (ii) For all cohorts, female sex, high education, extraversion, openness, agreeableness, and conscientiousness (Big Five) were associated positively with trait resilience. Childhood trauma, depressive symptoms, and neuroticism were associated negatively with trait resilience. (iii) In all cohorts, the level of intra-individual stability was moderate.Conclusion: We found that trait resilience was rather stable across decades of age in all cohorts, albeit intra-individual self-assessments agreed only moderately. We confirmed previous findings regarding negative and positive associations of personality and sociodemographic factors with trait resilience. [ABSTRACT FROM AUTHOR]

Neuroimaging studies have consistently reported similar brain structural abnormalities across different psychiatric disorders. Yet, the extent and regional distribution of shared morphometric abnormalities between disorders remains unknown. Here, we conducted a cross-disorder analysis of brain structural abnormalities in 6 psychiatric disorders based on effect size estimates for cortical thickness and subcortical volume differences between healthy control subjects and psychiatric patients from 11 mega- and meta-analyses from the ENIGMA (Enhancing Neuro Imaging Genetics Through Meta Analysis) consortium. Correlational and exploratory factor analyses were used to quantify the relative overlap in brain structural effect sizes between disorders and to identify brain regions with disorder-specific abnormalities. Brain structural abnormalities in major depressive disorder, bipolar disorder, schizophrenia, and obsessive-compulsive disorder were highly correlated (r =.443 to r =.782), and one shared latent underlying factor explained between 42.3% and 88.7% of the brain structural variance of each disorder. The observed shared morphometric signature of these disorders showed little similarity with brain structural patterns related to physiological aging. In contrast, patterns of brain structural abnormalities independent of all other disorders were observed in both attention-deficit/hyperactivity disorder and autism spectrum disorder. Brain regions showing high proportions of independent variance were identified for each disorder to locate disorder-specific morphometric abnormalities. Taken together, these results offer novel insights into transdiagnostic as well as disorder-specific brain structural abnormalities across 6 major psychiatric disorders. Limitations comprise the uncertain contribution of risk factors, comorbidities, and medication effects to the observed pattern of results that should be clarified by future research. [ABSTRACT FROM AUTHOR]

Objectives: Combinations of resting-state fMRI and machine-learning techniques are increasingly employed to develop diagnostic models for mental disorders. However, little is known about the neurobiological heterogeneity of depression and diagnostic machine learning has mainly been tested in homogeneous samples. Our main objective was to explore the inherent structure of a diverse unipolar depression sample. The secondary objective was to assess, if such information can improve diagnostic classification.Materials and Methods: We analyzed data from 360 patients with unipolar depression and 360 non-depressed population controls, who were subdivided into two independent subsets. Cluster analyses (unsupervised learning) of functional connectivity were used to generate hypotheses about potential patient subgroups from the first subset. The relationship of clusters with demographical and clinical measures was assessed. Subsequently, diagnostic classifiers (supervised learning), which incorporated information about these putative depression subgroups, were trained.Results: Exploratory cluster analyses revealed two weakly separable subgroups of depressed patients. These subgroups differed in the average duration of depression and in the proportion of patients with concurrently severe depression and anxiety symptoms. The diagnostic classification models performed at chance level.Limitations: It remains unresolved, if subgroups represent distinct biological subtypes, variability of continuous clinical variables or in part an overfitting of sparsely structured data.Conclusions: Functional connectivity in unipolar depression is associated with general disease effects. Cluster analyses provide hypotheses about potential depression subtypes. Diagnostic models did not benefit from this additional information regarding heterogeneity. [ABSTRACT FROM AUTHOR]

The aim of this study was to examine associations of major depressive disorder (MDD), its distinct subtypes, and symptom severity with the individual lifestyle factors smoking, diet quality, physical activity, and body mass index as well as with a combined lifestyle index measuring the co-occurrence of these lifestyle factors. A sample of 823 patients with MDD and 597 non-depressed controls was examined. The psychiatric assessment was based on a clinical interview including the Mini International Neuropsychiatric Interview and the Hamilton Depression Rating Scale. Each lifestyle factor was scored as either healthy or unhealthy, and the number of unhealthy lifestyle factors was added up in a combined lifestyle index. Cross-sectional analyses were performed using alternating logistic regression and ordinal logistic regression, adjusted for socio-demographic characteristics. After adjustment, MDD was significantly associated with smoking, low physical activity, and overweight. Likewise, MDD was significantly related to the overall lifestyle index. When stratifying for subtypes, all subtypes showed higher odds for an overall unhealthier lifestyle than controls, but the associations with the individual lifestyle factors were partly different. Symptom severity was associated with the lifestyle index in a dose-response manner. In conclusion, patients with MDD represent an important target group for lifestyle interventions. [ABSTRACT FROM AUTHOR]

Abstract: Background: Predictors of future stroke events gain importance in vascular medicine. Herein, we investigated the value of the ankle-brachial index (ABI), a simple non-invasive marker of atherosclerosis, as stroke predictor in addition to established risk factors that are part of the Framingham risk score (FRS). Methods: 4299 subjects from the population-based Heinz Nixdorf Recall study (45–75 years; 47.3% men) without previous stroke, coronary heart disease or myocardial infarcts were followed up for ischemic and hemorrhagic stroke events over 109.0 ± 23.3 months. Cox proportional hazard regressions were used to evaluate ABI as stroke predictor in addition to established vascular risk factors (age, sex, systolic blood pressure, LDL, HDL, diabetes, smoking). Results: 104 incident strokes (93 ischemic) occurred (incidence rate: 2.69/1000 person-years). Subjects suffering stroke had significantly lower ABI values at baseline than the remaining subjects (1.03 ± 0.22 vs. 1.13 ± 0.14, p < 0.001). In a multivariable Cox regression, ABI predicted stroke in addition to classical risk factors (hazard ratio = 0.77 per 0.1, 95% confidence interval = 0.69–0.86). ABI predicted stroke events in subjects above and below 65 years, both in men and women. ABI specifically influenced stroke risk in subjects belonging to the highest (>13%) and intermediate (8–13%) FRS tercile. In these subjects, stroke incidence was 28.13 and 8.13/1000 person-years, respectively, for ABI < 0.9, compared with 3.97 and 2.07/1000 person-years for 0.9 ≤ ABI ≤ 1.3. Conclusions: ABI predicts stroke in the general population, specifically in subjects with classical risk factors, where ABI identifies subjects at particularly high stroke risk. [Copyright &y& Elsevier]

Summary: Background: Sex hormones levels and the androgen receptor CAGn polymorphism have been shown to be involved in depressed mood in aging men. But the few prior studies found inconsistent results on the role of both factors. Methods: 186 male participants aged ≥65 years from the community based Memory and Morbidity in Augsburg Elderly (MEMO) Study underwent a physical examination, and a medical interview including two scales (Center for Epidemiologic Studies Depression Scale (CES-D); Activities of Daily Living Scale (ADL). Testosterone, SHBG and LH levels were measured and the androgen receptor CAGn polymorphism was genotyped. χ 2, Mann–Whitney U-test, Pearson's correlations and multivariable linear and logistic regression were used in the analysis. Results: Higher depressive scores were significantly associated with higher SHBG-levels (beta coefficient 0.25, p <0.001). SHBG alone explained 8% of variance of the CES-D depression score. Mortality at 10 years follow-up was predicted by higher SHBG levels, higher ADL-scores, older age, current smoking and the depression score at baseline. This model explained 35% of the variance of mortality. The number of CAG repeats was neither related to depression scores nor to mortality. Conclusions: We found positive associations between SHBG levels and old age male depression as well as mortality. Whether SHBG has a testosterone independent effect in this context should be investigated further. [Copyright &y& Elsevier]

Abstract: Objective: To investigate the association between the liver enzymes γ-glutamyltransferase (GGT) and (alanine aminotransferase) ALT and risk of stroke, its subtypes including TIA as well as fatal and non-fatal events. Methods: A case-cohort study within the European Prospective Investigation into Cancer and Nutrition-Potsdam Study comprising 27548 middle-aged subjects was designed. GGT and ALT were measured in plasma of 353 individuals who developed a stroke and in 2110 individuals who remained free of cardiovascular events during a mean follow-up of 8.2 ± 2.2 years. Cox proportional-hazard models were applied to evaluate the association between liver enzymes and stroke risk. Results: After adjustment for established clinical and lifestyle factors, a 1 unit change in naturally logged GGT was related to a 1.20 (95%CI: 1.03–1.40) increased stroke risk. Risk estimates did not significantly differ between fatal (Relative Risk (RR) = 1.35, 95%CI: 1.14–1.61) and non-fatal events (RR = 1.15; 95%CI: 0.97–1.36). ALT was not associated with overall stroke risk (RR = 0.95; 95%CI: 0.71–1.26). However, in subtype analyses we observed in multivariable adjusted models a significant increased risk of hemorrhagic stroke (RR = 2.00; 95% CI: 1.01–3.96), but decreased risk of ischemic stroke (RR = 0.66; 95%CI: 0.44–0.998). Conclusions: Our data provide further evidence for a link between GGT, but not ALT and overall stroke suggesting that these biomarkers are involved in different pathways of disease development. Further studies are needed to clarify the putative relationships between ALT and subtypes of stroke. [Copyright &y& Elsevier]

Abstract: Objective: A bidirectional relationship between depression and cardiovascular disease (CVD) including biological mechanisms has been proposed; however, the potential role of clinical and sociodemographic moderators in this relationship remains unclear. We aim to systematically review the moderating influence of the clinical and sociodemographic variables on the observed interrelationship between depressive disorders and CVD. Method: We systematically reviewed MEDLINE, The Cochrane Library and PsycINFO databases. After the exclusion of articles, 101 remained for this review. Results: Several studies suggest that clinical characteristics of depression, such as severity of depression, number of episodes and duration of depression, may moderate the relationship between depression and cardiovascular disease. Consistently, various studies support a role for marital status, education and income as moderators of this relationship. Several of these studies vary in methodology, hence yielding some inconsistent results. Longitudinal and controlled studies are required to investigate the effect sizes of these moderating factors on the depression–CVD relationship. Conclusions: Clinical characteristics of depression and sociodemographic factors appear to be moderators in the bidirectional relationship between depression and cardiovascular disease. Further research should consider these factors in conjunction with subtypes of depression and biological markers in a comprehensive model of this interrelationship. Our findings may assist with clinical decision-making processes. [Copyright &y& Elsevier]

Abstract: Objective: In multimorbidity indices, chronic conditions are often weighted according to their severity or their impact on different outcomes. These weights are mostly developed on the basis of only one study population by using very specific study participants, such as hospital patients. To overcome the limited validity of the indices, mean weights across five population-based studies were calculated according to the impact of diseases on self-reported health status. Study Design and Setting: Individual data was provided from the National Health Interview and Examination Survey (n =1,010), Dortmund Health Study (n =281), Memory and Morbidity in Augsburg Elderly Study (n =385), Survey of Health, Aging and Retirement in Europe Study (n =1,278), and Study of Health in Pomerania Study (n =962). By using logistic regression analysis, odds ratios (ORs) were calculated for reporting a fair or poor health status resulting from one of 10 different chronic conditions compared with a reference group without the specific disease, controlling for age and sex. If the results were homogenous across studies (I 2 <40%), significant pooled ORs were considered valid weights for a multimorbidity index. Results: Myocardial infarction has the highest impact on self-reported health status across studies with a pooled OR of 3.9, followed by chronic obstructive pulmonary disease (pooled OR: 3.1). A medium impact was observed for arthrosis, asthma, diabetes mellitus, and osteoporosis. Conclusion: This method provided valid weights for seven chronic conditions. [Copyright &y& Elsevier]

Abstract: Simplexity is an emerging concept that expresses a possible complementary relationship between complexity and simplicity. The brain has been known as the most complex structure, and tremendous effort has been spent to study how it works. By understanding complex function of the brain, one can hope to unravel the mystery of its diseases and its biological systems. We propose herein an entropy-based framework for analysis of complexity with a particular application to the study of white matter changes of the human brain. In this analysis, the proposed approach takes into account both morphological structure and image intensity values of MRI scans to construct the complexity profiles of the brain. It has been realized that the quantity and spatial distribution of white matter changes play an important role in cognitive decline (i.e. dementia) and other neuropsychiatric disorders (i.e. multiple sclerosis, depression) as well as in other dementia disorders such as Alzheimers disease. Thus, the results can be utilized as a tool for automated quantification and comparison of various spatial distributions and orientations of age-related white matter changes where manual analysis is difficult and leads to different sensitivities for the respective MRI-based information of the brain. [Copyright &y& Elsevier]

Abstract: The magnetic resonance imaging (MRI) of the brain is one of the important data items for studying memory and morbidity in elderly as these images can provide useful information through the quantitative measures of various regions of interest of the brain. As an effort to fully automate the biomedical analysis of the brain that can be combined with the genetic data of the same human population and where the records of the original MRI data are missing, this paper presents two effective methods for addressing this imaging problem. The first method handles the restoration of the film-copied MRI. The second method involves the segmentation of the image data. Experimental results and comparisons with other methods suggest the usefulness of the proposed image analysis methodology. [Copyright &y& Elsevier]

Abstract: Objectives: To investigate the associations between circulating cytokines and specific neuropsychological domains of cognitive functioning (memory, processing speed and motor function) and general cognitive function (MMSE) in healthy elderly individuals. Methods: In a cross-sectional study of 369 community dwelling elderly subjects, we examined the relationship between serum IL-1β, sIL-4R, IL-6, IL-8, IL-10, IL-12 and TNF-α concentrations and cognitive performance using an extensive standardized and validated cognitive test battery assessing memory, word fluency, perceptual/cognitive speed, attention and executive functioning, and motor speed. Results: Multivariate analysis adjusted for various confounders and Bonferroni correction for multiple comparisons demonstrated that increased serum concentrations of IL-8 were associated with poor performance in the memory and speed domains and in motor function. No significant associations were found between the remaining cytokines and domains of cognitive functioning. Global cognitive functioning, as measured with MMSE, was not associated with any cytokine. Conclusions: This study suggests an association between circulating IL-8 concentrations and cognitive dysfunction in the elderly. An interaction between this cytokine and glial cells may help explain the pathophysiological mechanisms leading to cognitive impairment in our study group. [Copyright &y& Elsevier]

Summary: This study is to investigate the associations between specific polymorphisms in three cytokine genes and domains of cognitive functioning in a population based study in the elderly. In a cross-sectional study of 369 community dwelling elderly subjects we examined the relationships between the polymorphisms IL-1β-1418C→T, IL-6-572G→C and TNF-α-308G→A and the cognitive function domains memory, processing speed and motor function using an extensive neuropsychological test battery. Linear regression models were used in the analysis and results adjusted for multiple comparisons. A significant association between the IL-1β-1418C→T polymorphism and memory performance was found with carriers of the T allele (dominant model) having worse memory performance than those with the C allele. In addition, a significant association between the TNF-α-308G→A polymorphism and processing speed was observed, indicating better performance for heterozygous or homozygous carriers of the A allele. These results remained significant after adjustment for known confounders of cognitive function and additional Bonferroni correction for multiple comparisons. Our study provides first results on detrimental effects of the IL-1β-1418C→T polymorphism on memory performance and neuroprotective effects of the TNF-α-308G→A polymorphism on processing speed in elderly individuals. Further research is needed to prospectively examine changes in cognitive performance in relation to cytokine genotypes. [Copyright &y& Elsevier]

Abstract: Aim of this study was to examine the association of symptom dimensions of depressive symptoms and cognitive functioning in the elderly. In a population-based study with 365 participants 65–83 years of age, dimensions of depressive symptoms were assessed with the four subscales of the CES-D-score and standardized cognitive tests assessing attention, memory, cognitive speed, and motor speed were performed. Compared to men, women scored significantly higher on the subscales for depressed affect and somatic complaints. Older participants had a significantly higher score for interpersonal difficulties. Participants with lower education had higher scores on all four psychological dimensions of depressive symptoms than those with high education (only significant for depressive affect). Individuals scoring high on CES-D subscales for depressive affect and somatic complaints had statistically significant (after Bonferroni adjustment) lower scores in attention and motor function in multivariate analyses. No significant associations between the symptom dimensions of positive affect and interpersonal difficulties with any of the cognitive tests were found in univariate and multivariate analyses (after Bonferroni adjustment). Our findings suggest specific patterns in the relationships between symptom dimensions of depressive symptoms and cognitive dysfunction in the general elderly population. This novel approach might be useful in addressing the heterogeneity of cognitive impairment in depression and in predicting cognitive outcome in depression. [Copyright &y& Elsevier]

Neurofilament M, a major component of Lewy bodies, represents an interesting candidate in the pathogenesis of Parkinson''s disease (PD). We performed detailed mutation analyses of the NF-M gene in 322 familial and sporadic PD patients. Two polymorphisms (Ala475Thr and Gly697Arg) occurred at similar frequencies in PD patients and controls. A Pro725Gln substitution and a deletion of valine in position 829 were identified in two PD patients. These substitutions affect residues of the NF-M protein that are highly conserved among different species. None of our patients carried the Gly336Ser substitution, which has been described in familial PD. Our results argue against a major role of NF-M in PD. However, rare variants of the NF-M gene may act as susceptibility factors for PD and functional analyses of the identified variations are warranted to decipher possible mechanisms in neurodegeneration. [Copyright &y& Elsevier]

Mutations in α-synuclein have been identified in some rare families with autosomal dominant Parkinson’s disease (PD). The synuclein gene family shares physical and functional homology with 14-3-3 proteins and binds to 14-3-3 proteins and to its ligands. We therefore investigated whether 14-3-3 proteins are also involved in the pathogenesis of PD. Here we demonstrate that 14-3-3 proteins are colocalized with Lewy bodies in PD. We investigated the 14-3-3 eta (YWHAH) gene by mutation analysis and association studies as it maps to human chromosome 22q12.1–q13.1, a region which has been recently implicated in PD and carried out immunohistochemical studies of Lewy bodies with two different 14-3-3 eta antibodies. In 358 sporadic and familial PD patients, disease causing mutations were not identified. Furthermore, association studies with intragenic polymorphisms do not provide evidence for an involvement of 14-3-3 eta in the pathogenesis of PD. In accordance with these findings, there was no staining of substantia nigra Lewy bodies with antibodies specific for the 14-3-3 eta subunit. [Copyright &y& Elsevier]

Mutations in two genes, α-synuclein and parkin, have been identified as some rare causes for familial Parkinson’s disease (PD). α-Synuclein and parkin protein have subsequently been identified in Lewy bodies (LB). To gain further insight into the pathogenesis of PD we investigated the role of neurofilament light (NF-L), another component of LB aggregation. A detailed mutation search of the NF-L gene in 328 sporadic and familial PD patients of German ancestry revealed three silent DNA changes (G163A, C224T, C487T) in three unrelated patients. Analysis of the promoter region of the NF-L gene identified a total of three base pair substitutions defining five haplotypes. Association studies based on these haplotypes revealed no significant differences between PD patients and 344 control individuals. Therefore, NF-L is unlikely to play a major role in the pathogenesis of PD. [Copyright &y& Elsevier]