Publications

959 Publications visible to you, out of a total of 959

Abstract (Expand)

Background: The P3 is related to cognitive functions, psychopathology and effects of cognition-improving and -impairing drugs. Studies assessing the chronic effects of smoking on P3 mostly reported a reduction of P3 amplitude for chronic and former smokers. To date, only a few studies have analyzed this impact by using a three-stimulus oddball paradigm. This study tries to replicate previous smoking associations applying an eyes-closed active three-stimulus oddball paradigm in a well-diagnosed population based sample of healthy elderly subjects who were allowed to smoke ad libitum. The study also tries to estimate whether smoking is a relevant confounder in P3 assessment within the analyzed sample. Methods: From the Leipzig Health Care Study (LIFE) current, former and non-smokers without mental or neurological disorders were matched by age, sex and qualification. Risky alcohol consumption was further exclusion criterion given the strong association between alcoholism and P3 amplitude reduction. Results: Smoking status was not associated with any P3 parameter, with exception of prolonged P3a latency at Fz in former smokers compared to never smokers. Also, there were no significant effects of smoking status on any of the behavioral measures or a correlation with smoking-related data. Discussion: This study indicates that smoking does not seem to relevantly impact the P3 components in non-abstaining healthy elderly subjects when confounders are controlled for.

Authors: N. Mauche, C. Sander, P. Jawinski, C. Enzenbach, S. Olbrich, P. Schonknecht, U. Hegerl, T. Hensch

Date Published: 1st Sep 2015

Publication Type: Not specified

Abstract (Expand)

BACKGROUND: Recently, biomarkers have been suggested to be incorporated into diagnostic criteria for Alzheimer's disease (AD). Regarding disease-specific brain amyloid-beta deposition these comprise low amyloid-beta 1-42 in cerebrospinal fluid (CSF) and positive positron emission tomography (PET) amyloid imaging, while neuronal degeneration is evidenced by high total and phosphorylated tau levels in CSF (t-/p-tau), regional hypometabolism ([(18)F]fluorodeoxyglucose PET, FDG-PET) and characteristic atrophy-patterns (magnetic resonance imaging, MRI). CASE PRESENTATION: Here we present a case of clinically and biomarker supported AD (CSF t-/p-tau, MRI, FDG-PET) in a 59-year-old Caucasian man in whom indicators of amyloid-beta deposition dissociated between CSF parameters and the respective PET imaging. CONCLUSIONS: Such cases highlight the necessity to better understand potential dissociations between PET and CSF data for amyloid-beta biomarkers, because they are currently considered interchangeably valid with regard to in-vivo evidence for AD pathology. This is more important since amyloid deposition markers can be considered a very first prognostic indicator of imminent AD, prior to neurodegenerative biomarkers and cognitive symptoms. The case illustrates the need for further longitudinal data on potential dissociations of AD biomarkers to devise recommendations for their better prognostic and diagnostic interpretation in the future.

Authors: M. L. Schroeter, S. Tiepolt, A. Marschhauser, A. Thone-Otto, K. T. Hoffmann, H. Barthel, H. Obrig, O. Sabri

Date Published: 26th Aug 2015

Publication Type: Not specified

Human Diseases: Alzheimer's disease

Abstract

Not specified

Authors: Indra Kraft, Riccardo Cafiero, Gesa Schaadt, Jens Brauer, Nicole E. Neef, Bent Müller, Holger Kirsten, Arndt Wilcke, Johannes Boltze, Angela D. Friederici, Michael A. Skeide

Date Published: 24th Aug 2015

Publication Type: Journal article

Abstract (Expand)

Genetics of gene expression (eQTLs or expression QTLs) has proved an indispensable tool for understanding biological pathways and pathomechanisms of trait-associated SNPs. However, power of most genome-wide eQTL studies is still limited. We performed a large eQTL study in peripheral blood mononuclear cells of 2112 individuals increasing the power to detect trans-effects genome-wide. Going beyond univariate SNP-transcript associations, we analyse relations of eQTLs to biological pathways, polygenetic effects of expression regulation, trans-clusters and enrichment of co-localized functional elements. We found eQTLs for about 85% of analysed genes, and 18% of genes were trans-regulated. Local eSNPs were enriched up to a distance of 5 Mb to the transcript challenging typically implemented ranges of cis-regulations. Pathway enrichment within regulated genes of GWAS-related eSNPs supported functional relevance of identified eQTLs. We demonstrate that nearest genes of GWAS-SNPs might frequently be misleading functional candidates. We identified novel trans-clusters of potential functional relevance for GWAS-SNPs of several phenotypes including obesity-related traits, HDL-cholesterol levels and haematological phenotypes. We used chromatin immunoprecipitation data for demonstrating biological effects. Yet, we show for strongly heritable transcripts that still little trans-chromosomal heritability is explained by all identified trans-eSNPs; however, our data suggest that most cis-heritability of these transcripts seems explained. Dissection of co-localized functional elements indicated a prominent role of SNPs in loci of pseudogenes and non-coding RNAs for the regulation of coding genes. In summary, our study substantially increases the catalogue of human eQTLs and improves our understanding of the complex genetic regulation of gene expression, pathways and disease-related processes.

Authors: H. Kirsten, H. Al-Hasani, L. Holdt, A. Gross, F. Beutner, K. Krohn, K. Horn, P. Ahnert, R. Burkhardt, K. Reiche, J. Hackermuller, M. Loffler, D. Teupser, J. Thiery, M. Scholz

Date Published: 15th Aug 2015

Publication Type: Journal article

Abstract (Expand)

Although human biomedical and physiological information is readily available, such information for great apes is limited. We analyzed clinical chemical biomarkers in serum samples from 277 wild- and captive-born great apes and from 312 healthy human volunteers as well as from 20 rhesus macaques. For each individual, we determined a maximum of 33 markers of heart, liver, kidney, thyroid and pancreas function, hemoglobin and lipid metabolism and one marker of inflammation. We identified biomarkers that show differences between humans and the great apes in their average level or activity. Using the rhesus macaques as an outgroup, we identified human-specific differences in the levels of bilirubin, cholinesterase and lactate dehydrogenase, and bonobo-specific differences in the level of apolipoprotein A-I. For the remaining twenty-nine biomarkers there was no evidence for lineage-specific differences. In fact, we find that many biomarkers show differences between individuals of the same species in different environments. Of the four lineage-specific biomarkers, only bilirubin showed no differences between wild- and captive-born great apes. We show that the major factor explaining the human-specific difference in bilirubin levels may be genetic. There are human-specific changes in the sequence of the promoter and the protein-coding sequence of uridine diphosphoglucuronosyltransferase 1 (UGT1A1), the enzyme that transforms bilirubin and toxic plant compounds into water-soluble, excretable metabolites. Experimental evidence that UGT1A1 is down-regulated in the human liver suggests that changes in the promoter may be responsible for the human-specific increase in bilirubin. We speculate that since cooking reduces toxic plant compounds, consumption of cooked foods, which is specific to humans, may have resulted in relaxed constraint on UGT1A1 which has in turn led to higher serum levels of bilirubin in humans.   Although human biomedical and physiological information is readily available, such information for great apes is limited. We analyzed clinical chemical biomarkers in serum samples from 277 wild- and captive-born great apes and from 312 healthy human volunteers as well as from 20 rhesus macaques. For each individual, we determined a maximum of 33 markers of heart, liver, kidney, thyroid and pancreas function, hemoglobin and lipid metabolism and one marker of inflammation. We identified biomarkers that show differences between humans and the great apes in their average level or activity. Using the rhesus macaques as an outgroup, we identified human-specific differences in the levels of bilirubin, cholinesterase and lactate dehydrogenase, and bonobo-specific differences in the level of apolipoprotein A-I. For the remaining twenty-nine biomarkers there was no evidence for lineage-specific differences. In fact, we find that many biomarkers show differences between individuals of the same species in different environments. Of the four lineage-specific biomarkers, only bilirubin showed no differences between wild- and captive-born great apes. We show that the major factor explaining the human-specific difference in bilirubin levels may be genetic. There are human-specific changes in the sequence of the promoter and the protein-coding sequence of uridine diphosphoglucuronosyltransferase 1 (UGT1A1), the enzyme that transforms bilirubin and toxic plant compounds into water-soluble, excretable metabolites. Experimental evidence that UGT1A1 is down-regulated in the human liver suggests that changes in the promoter may be responsible for the human-specific increase in bilirubin. We speculate that since cooking reduces toxic plant compounds, consumption of cooked foods, which is specific to humans, may have resulted in relaxed constraint on UGT1A1 which has in turn led to higher serum levels of bilirubin in humans. //  Although human biomedical and physiological information is readily available, such information for great apes is limited. We analyzed clinical chemical biomarkers in serum samples from 277 wild- and captive-born great apes and from 312 healthy human volunteers as well as from 20 rhesus macaques. For each individual, we determined a maximum of 33 markers of heart, liver, kidney, thyroid and pancreas function, hemoglobin and lipid metabolism and one marker of inflammation. We identified biomarkers that show differences between humans and the great apes in their average level or activity. Using the rhesus macaques as an outgroup, we identified human-specific differences in the levels of bilirubin, cholinesterase and lactate dehydrogenase, and bonobo-specific differences in the level of apolipoprotein A-I. For the remaining twenty-nine biomarkers there was no evidence for lineage-specific differences. In fact, we find that many biomarkers show differences between individuals of the same species in different environments. Of the four lineage-specific biomarkers, only bilirubin showed no differences between wild- and captive-born great apes. We show that the major factor explaining the human-specific difference in bilirubin levels may be genetic. There are human-specific changes in the sequence of the promoter and the protein-coding sequence of uridine diphosphoglucuronosyltransferase 1 (UGT1A1), the enzyme that transforms bilirubin and toxic plant compounds into water-soluble, excretable metabolites. Experimental evidence that UGT1A1 is down-regulated in the human liver suggests that changes in the promoter may be responsible for the human-specific increase in bilirubin. We speculate that since cooking reduces toxic plant compounds, consumption of cooked foods, which is specific to humans, may have resulted in relaxed constraint on UGT1A1 which has in turn led to higher serum levels of bilirubin in humans.

Authors: Claudius Ronke, Michael Dannemann, Michel Halbwax, Anne Fischer, Christin Helmschrodt, Mathias Brügel, Claudine André, Rebeca Atencia, Lawrence Mugisha, Markus Scholz, Uta Ceglarek, Joachim Thiery, Svante Pääbo, Kay Prüfer, Janet Kelso

Date Published: 6th Aug 2015

Publication Type: Journal article

Abstract (Expand)

The Three-Factor-Eating-Questionnaire (TFEQ) is an established instrument to assess eating behaviour. Analysis of the TFEQ-factor structure was based on selected, convenient and clinical samples so far. Aims of this study were (I) to analyse the factor structure of the German version of the TFEQ and (II)--based on the refined factor structure--to examine the association between eating behaviour and the body mass index (BMI) in a general population sample of 3,144 middle-aged and older participants (40-79 years) of the ongoing population based cohort study of the Leipzig Research Center for Civilization Diseases (LIFE Health Study). The factor structure was examined in a split-half analysis with both explorative and confirmatory factor analysis. Associations between TFEQ-scores and BMI values were tested with multiple regression analyses controlled for age, gender, and education. We found a three factor solution for the TFEQ with an 'uncontrolled eating', a 'cognitive restraint' and an 'emotional eating' domain including 29 of the original 51 TFEQ-items. Scores of the 'uncontrolled eating domain' showed the strongest correlation with BMI values (partial r = 0.26). Subjects with scores above the median in both 'uncontrolled eating' and 'emotional eating' showed the highest BMI values (mean = 29.41 kg/m(2)), subjects with scores below the median in all three domains showed the lowest BMI values (mean = 25.68 kg/m(2); F = 72.074, p<0.001). Our findings suggest that the TFEQ is suitable to identify subjects with specific patterns of eating behaviour that are associated with higher BMI values. Such information may help health care professionals to develop and implement more tailored interventions for overweight and obese individuals.

Authors: A. Loffler, T. Luck, F. S. Then, C. Sikorski, P. Kovacs, Y. Bottcher, J. Breitfeld, A. Tonjes, A. Horstmann, M. Loffler, C. Engel, J. Thiery, A. Villringer, M. Stumvoll, S. G. Riedel-Heller

Date Published: 1st Aug 2015

Publication Type: Not specified

Abstract (Expand)

BACKGROUND: Adhering to the Mediterranean diet (MeDi) is known to be beneficial with regard to many age-associated diseases including cardiovascular diseases and type 2 diabetes. Recent studies also suggest an impact on cognition and brain structure, and increasing effort is made to track effects down to single nutrients. AIMS: We aimed to review whether two MeDi components, i.e., long-chain omega-3 fatty acids (LC-n3-FA) derived from sea-fish, and plant polyphenols including resveratrol (RSV), exert positive effects on brain health in aging. CONTENT: We summarized health benefits associated with the MeDi and evaluated available studies on the effect of (1) fish-consumption and LC-n3-FA supplementation as well as (2) diet-derived or supplementary polyphenols such as RSV, on cognitive performance and brain structure in animal models and human studies. Also, we discussed possible underlying mechanisms. CONCLUSION: A majority of available studies suggest that consumption of LC-n3-FA with fish or fishoil-supplements exerts positive effects on brain health and cognition in older humans. However, more large-scale randomized controlled trials are needed to draw definite recommendations. Considering polyphenols and RSV, only few controlled studies are available to date, yet the evidence based on animal research and first interventional human trials is promising and warrants further investigation. In addition, the concept of food synergy within the MeDi encourages future trials that evaluate the impact of comprehensive lifestyle patterns to help maintaining cognitive functions into old age.

Authors: S. Huhn, S. Kharabian Masouleh, M. Stumvoll, A. Villringer, A. V. Witte

Date Published: 29th Jul 2015

Publication Type: Not specified

Human Diseases: cardiovascular system disease, diabetes mellitus

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