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1005 Publications visible to you, out of a total of 1005
In-vivo Dynamics of the Human Hippocampus across the Menstrual Cycle.
LIFE Adult

Abstract (Expand)

Sex hormones fluctuate during the menstrual cycle. Evidence from animal studies suggests similar subtle fluctuations in hippocampal structure, predominantly linked to estrogen. Hippocampal abnormalities … have been observed in several neuropsychiatric pathologies with prominent sexual dimorphism. Yet, the potential impact of subtle sex-hormonal fluctuations on human hippocampal structure in health is unclear. We tested the feasibility of longitudinal neuroimaging in conjunction with rigorous menstrual cycle monitoring to evaluate potential changes in hippocampal microstructure associated with physiological sex-hormonal changes. Thirty longitudinal diffusion weighted imaging scans of a single healthy female subject were acquired across two full menstrual cycles. We calculated hippocampal fractional anisotropy (FA), a measure sensitive to changes in microstructural integrity, and investigated potential correlations with estrogen. We observed a significant positive correlation between FA values and estrogen in the hippocampus bilaterally, revealing a peak in FA closely paralleling ovulation. This exploratory, single-subject study demonstrates the feasibility of a longitudinal DWI scanning protocol across the menstrual cycle and is the first to link subtle endogenous hormonal fluctuations to changes in FA in vivo. In light of recent attempts to neurally phenotype single humans, our findings highlight menstrual cycle monitoring in parallel with highly sampled individual neuroimaging data to address fundamental questions about the dynamics of plasticity in the adult brain.

Authors: C. Barth, C. J. Steele, K. Mueller, V. P. Rekkas, K. Arelin, A. Pampel, I. Burmann, J. Kratzsch, A. Villringer, J. Sacher

Date Published: 7th Oct 2016

Publication Type: Not specified

Differential Risk of Incident Alzheimer's Disease Dementia in Stable Versus Unstable Patterns of Subjective Cognitive Decline.
LIFE Adult

Abstract (Expand)

BACKGROUND: It is unknown whether longitudinal stability versus instability in subjective cognitive decline (SCD) is a modifying factor of the association between SCD and risk of incident Alzheimer's … disease (AD) dementia. OBJECTIVE: We tested the modifying role of temporal stability of the SCD report on AD dementia risk in cognitively normal elderly individuals. METHODS: We analyzed data of 1,990 cognitively normal participants from the longitudinal AgeCoDe Study. We assessed SCD with/without associated worries both at baseline and first follow-up 18 months later. Participants were then classified either as (a) Controls (CO, with no SCD at both baseline and follow-up 1, n = 613), (b) inconsistent SCD (with SCD reported only at baseline or at follow-up 1, n = 637), (c) consistent SCD but without/or with inconsistent worries (n = 610) or (d) consistent SCD with worries (n = 130). We estimated incident AD dementia risk over up to 6 years for each group with Cox-Proportional Hazard Regression analyses adjusted for age, gender, education, ApoE4 status, and depression. RESULTS: Compared to CO, inconsistent SCD was not associated with increased risk of incident AD dementia. In contrast, risk was doubled in the group of consistent SCD without/ with inconsistent worries, and almost 4-fold in the group of consistent SCD with worries. These results could be replicated when using follow-up 1 to follow-up 2 response patterns for group definition. CONCLUSION: These findings suggest that longitudinal stability versus instability is an important modifying factor of the association between SCD and AD dementia risk. Worrisome SCD that is also consistently reported over time is associated with greatly increased risk of AD dementia.

Authors: S. Wolfsgruber, L. Kleineidam, M. Wagner, E. Mosch, H. Bickel, D. Lupsilonhmann, A. Ernst, B. Wiese, S. Steinmann, H. H. Konig, C. Brettschneider, T. Luck, J. Stein, S. Weyerer, J. Werle, M. Pentzek, A. Fuchs, W. Maier, M. Scherer, S. G. Riedel-Heller, F. Jessen

Date Published: 4th Oct 2016

Publication Type: Journal article

Human Diseases: dementia, Alzheimer's disease

Incidence of severe sepsis and septic shock in German intensive care units: the prospective, multicentre INSEP study.
SepNet - German Competence Network Sepsis

Abstract (Expand)

PURPOSE: To estimate the incidence density, point prevalence and outcome of severe sepsis and septic shock in German intensive care units (ICUs). METHODS: In a prospective, multicentre, longitudinal … observational study, all patients already on the ICU at 0:00 on 4 November 2013 and all patients admitted to a participating ICU between 0:00 on 4 November 2013 and 2359 hours on 1 December 2013 were included. The patients were followed up for the occurrence of severe sepsis or septic shock (SEPSIS-1 definitions) during their ICU stay. RESULTS: A total of 11,883 patients from 133 ICUs at 95 German hospitals were included in the study, of whom 1503 (12.6 %) were diagnosed with severe sepsis or septic shock. In 860 cases (57.2 %) the infections were of nosocomial origin. The point prevalence was 17.9 % (95 % CI 16.3-19.7).The calculated incidence rate of severe sepsis or septic shock was 11.64 (95 % CI 10.51-12.86) per 1000 ICU days. ICU mortality in patients with severe sepsis/septic shock was 34.3 %, compared with 6 % in those without sepsis. Total hospital mortality of patients with severe sepsis or septic shock was 40.4 %. Classification of the septic shock patients using the new SEPSIS-3 definitions showed higher ICU and hospital mortality (44.3 and 50.9 %). CONCLUSIONS: Severe sepsis and septic shock continue to be a frequent syndrome associated with high hospital mortality. Nosocomial infections play a major role in the development of sepsis. This study presents a pragmatic, affordable and feasible method for the surveillance of sepsis epidemiology. Implementation of the new SEPSIS-3 definitions may have a major effect on future epidemiological data.

Editor:

Date Published: 1st Oct 2016

Publication Type: Journal article

Human Diseases: disease by infectious agent

Genetic Factors of the Disease Course after Sepsis: A Genome-Wide Study for 28Day Mortality
Genetical Statistics and Systems Biology

Abstract (Expand)

Sepsis is the dysregulated host response to an infection which leads to life-threatening organ dysfunction that varies by host genomic factors. We conducted a genome-wide association study (GWAS) in … 740 adult septic patients and focused on 28day mortality as outcome. Variants with suggestive evidence for an association (p\textless/=10-5) were validated in two additional GWA studies (n=3470) and gene coding regions related to the variants were assessed in an independent exome sequencing study (n=74). In the discovery GWAS, we identified 243 autosomal variants which clustered in 14 loci (p\textless/=10-5). The best association signal (rs117983287; p=8.16x10-8) was observed for a missense variant located at chromosome 9q21.2 in the VPS13A gene. VPS13A was further supported by additional GWAS (p=0.03) and sequencing data (p=0.04). Furthermore, CRISPLD2 (p=5.99x10-6) and a region on chromosome 13q21.33 (p=3.34x10-7) were supported by both our data and external biological evidence. We found 14 loci with suggestive evidence for an association with 28day mortality and found supportive, converging evidence for three of them in independent data sets. Elucidating the underlying biological mechanisms of VPS13A, CRISPLD2, and the chromosome 13 locus should be a focus of future research activities.   Sepsis is the dysregulated host response to an infection which leads to life-threatening organ dysfunction that varies by host genomic factors. We conducted a genome-wide association study (GWAS) in 740 adult septic patients and focused on 28day mortality as outcome. Variants with suggestive evidence for an association (p\textless/=10-5) were validated in two additional GWA studies (n=3470) and gene coding regions related to the variants were assessed in an independent exome sequencing study (n=74). In the discovery GWAS, we identified 243 autosomal variants which clustered in 14 loci (p\textless/=10-5). The best association signal (rs117983287; p=8.16x10-8) was observed for a missense variant located at chromosome 9q21.2 in the VPS13A gene. VPS13A was further supported by additional GWAS (p=0.03) and sequencing data (p=0.04). Furthermore, CRISPLD2 (p=5.99x10-6) and a region on chromosome 13q21.33 (p=3.34x10-7) were supported by both our data and external biological evidence. We found 14 loci with suggestive evidence for an association with 28day mortality and found supportive, converging evidence for three of them in independent data sets. Elucidating the underlying biological mechanisms of VPS13A, CRISPLD2, and the chromosome 13 locus should be a focus of future research activities. //  Sepsis is the dysregulated host response to an infection which leads to life-threatening organ dysfunction that varies by host genomic factors. We conducted a genome-wide association study (GWAS) in 740 adult septic patients and focused on 28day mortality as outcome. Variants with suggestive evidence for an association (p\textless/=10-5) were validated in two additional GWA studies (n=3470) and gene coding regions related to the variants were assessed in an independent exome sequencing study (n=74). In the discovery GWAS, we identified 243 autosomal variants which clustered in 14 loci (p\textless/=10-5). The best association signal (rs117983287; p=8.16x10-8) was observed for a missense variant located at chromosome 9q21.2 in the VPS13A gene. VPS13A was further supported by additional GWAS (p=0.03) and sequencing data (p=0.04). Furthermore, CRISPLD2 (p=5.99x10-6) and a region on chromosome 13q21.33 (p=3.34x10-7) were supported by both our data and external biological evidence. We found 14 loci with suggestive evidence for an association with 28day mortality and found supportive, converging evidence for three of them in independent data sets. Elucidating the underlying biological mechanisms of VPS13A, CRISPLD2, and the chromosome 13 locus should be a focus of future research activities.

Authors: Andre Scherag, Franziska Schoneweck, Miriam Kesselmeier, Stefan Taudien, Matthias Platzer, Marius Felder, Christoph Sponholz, Anna Rautanen, Adrian V. S. Hill, Charles J. Hinds, Hamid Hossain, Norbert Suttorp, Oliver Kurzai, Hortense Slevogt, Evangelos J. Giamarellos-Bourboulis, Apostolos Armaganidis, Evelyn Trips, Markus Scholz, Frank M. Brunkhorst

Date Published: 1st Oct 2016

Publication Type: Journal article

NRSN1 associated grey matter volume of the visual word form area reveals dyslexia before school
Genetical Statistics and Systems Biology

Abstract (Expand)

Literacy learning depends on the flexibility of the human brain to reconfigure itself in response to environmental influences. At the same time, literacy and disorders of literacy acquisition are … heritable and thus to some degree genetically predetermined. Here we used a multivariate non-parametric genetic model to relate literacy-associated genetic variants to grey and white matter volumes derived by voxel-based morphometry in a cohort of 141 children. Subsequently, a sample of 34 children attending grades 4 to 8, and another sample of 20 children, longitudinally followed from kindergarten to first grade, were classified as dyslexics and controls using linear binary support vector machines. The NRSN1-associated grey matter volume of the ’visual word form area’ achieved a classification accuracy of ~ 73% in literacy-experienced students and distinguished between later dyslexic individuals and controls with an accuracy of 75% at kindergarten age. These findings suggest that the cortical plasticity of a region vital for literacy might be genetically modulated, thereby potentially preconstraining literacy outcome. Accordingly, these results could pave the way for identifying and treating the most common learning disorder before it manifests itself in school.   Literacy learning depends on the flexibility of the human brain to reconfigure itself in response to environmental influences. At the same time, literacy and disorders of literacy acquisition are heritable and thus to some degree genetically predetermined. Here we used a multivariate non-parametric genetic model to relate literacy-associated genetic variants to grey and white matter volumes derived by voxel-based morphometry in a cohort of 141 children. Subsequently, a sample of 34 children attending grades 4 to 8, and another sample of 20 children, longitudinally followed from kindergarten to first grade, were classified as dyslexics and controls using linear binary support vector machines. The NRSN1-associated grey matter volume of the ’visual word form area’ achieved a classification accuracy of ~ 73% in literacy-experienced students and distinguished between later dyslexic individuals and controls with an accuracy of 75% at kindergarten age. These findings suggest that the cortical plasticity of a region vital for literacy might be genetically modulated, thereby potentially preconstraining literacy outcome. Accordingly, these results could pave the way for identifying and treating the most common learning disorder before it manifests itself in school. //  Literacy learning depends on the flexibility of the human brain to reconfigure itself in response to environmental influences. At the same time, literacy and disorders of literacy acquisition are heritable and thus to some degree genetically predetermined. Here we used a multivariate non-parametric genetic model to relate literacy-associated genetic variants to grey and white matter volumes derived by voxel-based morphometry in a cohort of 141 children. Subsequently, a sample of 34 children attending grades 4 to 8, and another sample of 20 children, longitudinally followed from kindergarten to first grade, were classified as dyslexics and controls using linear binary support vector machines. The NRSN1-associated grey matter volume of the ’visual word form area’ achieved a classification accuracy of ~ 73% in literacy-experienced students and distinguished between later dyslexic individuals and controls with an accuracy of 75% at kindergarten age. These findings suggest that the cortical plasticity of a region vital for literacy might be genetically modulated, thereby potentially preconstraining literacy outcome. Accordingly, these results could pave the way for identifying and treating the most common learning disorder before it manifests itself in school.

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

Date Published: 26th Sep 2016

Publication Type: Journal article

The Cognitive Functioning of Socially Isolated Individuals may Profit from High Mental Work Demands
LIFE Adult

Abstract (Expand)

Objectives: Previous studies have shown that individuals with poor social relationships have an increased risk for dementia. Dementia risk, however, can also be positively influenced by lifestyle … factors. One such very important factor is high mental demands at work, in particular as the work environment affects a very long lifetime period. Thus, our objective was to investigate whether the cognitive functioning of socially isolated individuals may profit from high mental work demands. Methods: Analyses were based on n = 10,000 participants (aged 40 – 80 years) of the population-based German LIFE-Adult-Study. All participants underwent medical examinations and filled out standardized questionnaires. Cognitive functioning was assessed via the Verbal Fluency Test (VFT) and the Trail-Making Test (TMT). Social relationships were assessed via the Lubben Social Network Scale (LSNS-6). The interaction between social isolation and mental demands on cognitive functioning was analyzed via multivariate regression analyses. Results: The difference in cognitive functioning between high and low mental work demand conditions was larger in socially isolated individuals (VFT: 2.7 words, TMT-B: 26 seconds) compared to socially well integrated individuals (VFT: 2.1 words, TMT-B: 9 seconds). Multivariate regression analyses – adjusted for age, gender, and education – indicated that both mental work demands as well as social relationships are significantly associated with the level of cognitive functioning (p < 0.001). Results also suggest interaction effects indicating a stronger impact of mental work demands on cognitive functioning in socially isolated individuals than in well integrated individuals. Conclusion: The findings imply that individuals with poor social relationships may particularly benefit from high mental work demands regarding their risk for dementia. The level of mental demands at work could therefore be an important target for tailored preventative approaches.

Authors: F. S. Then, M. L. Schroeter, V. Witte, C. Engel, M. Loeffler, J. Thiery, A. Villringer, T. Luck, S. G. Riedel-Heller

Date Published: 15th Sep 2016

Publication Type: Journal article

Myocardial Infarction-Associated Circular RNA Predicting Left Ventricular Dysfunction.
Genetical Statistics and Systems Biology, LIFE Heart

Abstract

Not specified

Authors: M. Vausort, A. Salgado-Somoza, L. Zhang, P. Leszek, M. Scholz, A. Teren, R. Burkhardt, J. Thiery, D. R. Wagner, Y. Devaux

Date Published: 13th Sep 2016

Publication Type: Journal article

Human Diseases: left ventricular noncompaction, myocardial infarction

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