Publications

265 Publications visible to you, out of a total of 265

Abstract (Expand)

Obesity is known to affect the brain's gray matter (GM) and white matter (WM) structure but the interrelationship of such changes remains unclear. Here we used T1-weighted magnetic resonance imaging (MRI) in combination with voxel-based morphometry (VBM) and diffusion-tensor imaging (DTI) with tract-based spatial statistics (TBSS) to assess the relationship between obesity-associated alterations of gray matter density (GMD) and anisotropic water diffusion in WM, respectively. In a small cohort of lean to obese women, we confirmed previous reports of obesity-associated alterations of GMD in brain regions involved in executive control (i.e., dorsolateral prefrontal cortex, DLPFC) and habit learning (i.e., dorsal striatum). Gray matter density alterations of the DLPFC were negatively correlated with radial diffusivity in the entire corpus callosum. Within the genu of the corpus callosum we found a positive correlation with axial diffusivity. In posterior region and inferior areas of the body of the corpus callosum, axial diffusivity correlated negatively with altered GMD in the dorsal striatum. These findings suggest that, in women, obesity-related alterations of GMD in brain regions involved in executive control and habit learning might relate to alterations of associated WM fiber bundles within the corpus callosum.

Authors: K. Mueller, A. Horstmann, H. E. Moller, A. Anwander, J. Lepsien, M. L. Schroeter, A. Villringer, B. Pleger

Date Published: 11th Dec 2014

Publication Type: Not specified

Human Diseases: obesity

Abstract (Expand)

Midlife obesity has often been associated with accelerated cognitive decline during aging. Obesity leads to changes in multiple physiological factors that could impact neuronal tissue. Numerous studies have linked obesity and higher body mass index (BMI) with differences in cognitive functions and brain structure, including total brain volume, regional gray matter volume and white matter (WM) microstructure. However, regarding to WM, the available neuroimaging studies incorporated mainly small sample sizes that yielded less conclusive results. Thus, we investigated the association of obesity, measured using BMI and waist to hip ratio (WHR), with changes in WM microstructure, as well as variance in cognitive test scores in a large cohort of community-dwelling healthy individuals older than 60 years.

Authors: Rui Zhang, L. Lampe, Frauke Beyer, Sebastian Huhn, S. K. Masouleh, T. Luck, S. G. Riedel-Heller, Markus Löffler, M. L. Schroeter

Date Published: 28th Nov 2016

Publication Type: Not specified

Human Diseases: obesity

Abstract (Expand)

PURPOSE: The Sniffin' Sticks Screening 12 test is a test of olfactory performance based on pen-like odor dispensing devices. The aims of this study were to analyze the performance of this test in a general population sample and to explore associations between olfactory dysfunction and quality of life. METHODS: A large community sample (n = 7267) completed the Sniffin' Sticks Screening 12 test and several questionnaires measuring quality of life, anxiety, dispositional optimism, social support, and satisfaction with life. RESULTS: According to the criteria recommended by the test manufacturer, 5.1% of the participants were anosmic (score </= 6), 52.4% were dysosmic (7 </= score </= 10), and 42.5% were normosmic (score >/= 11). While frequencies of correct identification differed between the 12 sticks, all sticks contributed positively to the test results. The associations between olfactory functioning and quality of life variables were negligible. In the multivariate analyses, none of the associations reached the 1% significance level. CONCLUSIONS: While studies with patients in otorhinolaryngological clinics often report substantial detriments to their quality of life in relation to olfactory dysfunction, the present epidemiological study cannot confirm this association for the general population.

Authors: A. Hinz, T. Luck, S. G. Riedel-Heller, P. Y. Herzberg, C. Rolffs, K. Wirkner, C. Engel

Date Published: 21st Nov 2018

Publication Type: Not specified

Abstract (Expand)

BACKGROUND: Studies in older adults or those with cognitive impairment have shown associations between cognitive and olfactory performance, but there are few population-based studies especially in younger adults. We therefore cross-sectionally analyzed this association using data from the population-based LIFE-Adult-Study. METHODS: Cognitive assessments comprised tests from the Consortium to Establish a Registry for Alzheimer's Disease (CERAD): verbal fluency (VF), word list learning and recall (WLL, WLR), and the Trail Making Tests (TMT) A and B. The "Sniffin' Sticks Screening 12" test was used to measure olfactory performance. Linear regression analyses were performed to determine associations between the number of correctly identified odors (0 to 12) and the five cognitive test scores, adjusted for sex, age, education, and the presence of depressive symptoms. Receiver operating characteristic (ROC) analysis was carried out to determine the discriminative performance of the number of correctly identified odors regarding identification of cognition impairment. RESULTS: A total of 6783 participants (51.3% female) completed the olfaction test and the VF test and TMT. A subgroup of 2227 participants (46.9% female) also completed the WLL and WLR tests. Based on age-, sex-, and education-specific norms from CERAD, the following numbers of participants were considered cognitively impaired: VF 759 (11.2%), WLL 242 (10.9%), WLR: 132 (5.9%), TMT-A 415 (6.1%), and TMT-B/A ratio 677 (10.0%). On average, score values for VF were higher by 0.42 points (p < 0.001), for WLL higher by 0.32 points (p = 0.001), for WLR higher by 0.31 points (p = 0.002), for TMT-A lower by 0.25 points (p < 0.001), and for TMT-B/A ratio lower by 0.01 points (p < 0.001) per number of correctly identified odors. ROC analysis revealed area under the curve values from 0.55 to 0.62 for the five cognitive tests. CONCLUSIONS: Better olfactory performance was associated with better cognitive performance in all five tests in adults - adjusted for age, sex, education, and the presence of depressive symptoms. However, the ability of the smell test to discriminate between individuals with and without cognitive impairment was limited. The value of olfactory testing in early screening for cognitive impairment should be investigated in longitudinal studies.

Authors: M. Yahiaoui-Doktor, T. Luck, S. G. Riedel-Heller, M. Loeffler, K. Wirkner, C. Engel

Date Published: 10th May 2019

Publication Type: Not specified

Human Diseases: Alzheimer's disease

Abstract (Expand)

LIFE is an epidemiological study determining thousands of Leipzig inhabitants with a wide spectrum of interviews, questionnaires, and medical investigations. The heterogeneous data are centrally integrated into a research database and are analyzed by specific analysis projects. To semantically describe the large set of data, we have developed an ontological framework. Applicants of analysis projects and other interested people can use the LIFE Investigation Ontology (LIO) as central part of the framework to get insights, which kind of data is collected in LIFE. Moreover, we use the framework to generate queries over the collected scientific data in order to retrieve data as requested by each analysis project. A query generator transforms the ontological specifications using LIO to database queries which are implemented as project-specific database views. Since the requested data is typically complex, a manual query specification would be very timeconsuming, error-prone, and is, therefore, unsuitable in this large project. We present the approach, overview LIO and show query formulation and transformation. Our approach runs in production mode for two years in LIFE.

Authors: Toralf Kirsten, A. Uciteli

Date Published: 2015

Publication Type: Not specified

Abstract (Expand)

Background/Objective: The Life Orientation Test-Revised (LOT-R) is often used to assess dispositional optimism. The aims of this study were to test psychometric properties of the LOT-R, to provide normative scores, and to test the association between optimism and several psychological, sociodemographic, and behavioral factors. Method: A randomly selected German general population community sample with an age range of 18-80 years (N = 9,711) was surveyed. Results: The Confirmatory Factor Analysis (CFA) proved two (correlated) factors: Optimism and Pessimism. Invariance tests across gender and age groups confirmed metric invariance. There were only small gender differences in the LOT-R total score (M = 16.4 for females and M = 16.1 for males). The correlation between the subscales Optimism and Pessimism was strong for young and well educated people. Low optimism mean scores were observed for unemployed people, people with low income, smokers, and obese people. Normative scores of the LOT-R are provided. Conclusions: The study confirmed the bidimensional structure of the LOT-R and invariance across age and gender. We can recommend using this instrument for measuring dispositional optimism and pessimism in epidemiological research and clinical practice.

Authors: A. Hinz, C. Sander, H. Glaesmer, E. Brähler, M. Zenger, A. Hilbert, R. D. Kocalevent

Date Published: 1st May 2017

Publication Type: Journal article

Abstract (Expand)

Speckle tracking echocardiography (STE) is a widespread method for calculating myocardial strains and estimating left ventricle function. Since echocardiographic clips are corrupted by speckle decorrelation noise, resulting in irregular, nonphysiological tissue displacement fields, smoothing is performed on the displacement data, affecting the strain results. Thus, strain results may depend on the specific implementations of 2-D STE, as well as other systems' characteristics of the various vendors. A novel algorithm (called K-SAD) is introduced, which integrates the physiological constraint of smoothness of the displacement field into an optimization process. Simulated B-mode clips, modeling healthy and abnormal cases, were processed by K-SAD. Peak global and subendocardial longitudinal strains, as well as regional strains, were calculated. In addition, 410 healthy subjects were also processed. The results of K-SAD are compared with those of one of the leading commercial product. K-SAD provides global mid-wall strain values, as well as subendocardial and regional strain values, all in good agreement with the ground-truth-simulated phantom data. K-SAD peak global longitudinal systolic strain values for 410 healthy subjects are quite similar for the different regions: - 17.02 +/- 4.02%, - 19.00 +/- 3.45%, and - 19.72 +/- 5.06% at the basal, mid, and apical regions, respectively. Improved performance under noisy conditions was demonstrated by comparing a subgroup of 40 subjects with the best image quality with the remaining 370 cohort: K-SAD provides statistically similar global and regional results for the two cohorts. Our study indicates that the sensitivity of strain values to speckle noise, caused by the post block-matching weighted smoothing, can be significantly reduced and accuracy enhanced by employing an integrated one-stage, physiologically constrained optimization process.

Authors: H. Khamis, S. Shimoni, A. Hagendorff, N. Smirin, Z. Friedman, D. Adam

Date Published: 24th May 2016

Publication Type: Journal article

Abstract (Expand)

BACKGROUND: Subjective cognitive decline (SCD), i.e., the self-perceived feeling of worsening cognitive function, may be the first notable syndrome of preclinical Alzheimer's disease and other dementias. However, not all individuals with SCD progress. Stability of SCD, i.e., repeated reports of SCD, could contribute to identify individuals at risk, as stable SCD may more likely reflect the continuous neurodegenerative process of Alzheimer's and other dementias. METHODS: Cox regression analyses were used to assess the association between stability of SCD and progression to MCI and dementia in data derived from the population-based Leipzig Longitudinal Study of the Aged (LEILA75+). RESULTS: Of 453 cognitively unimpaired individuals with a mean age of 80.5 years (SD = 4.2), 139 (30.7 %) reported SCD at baseline. Over the study period (M = 4.8 years, SD = 2.2), 84 (18.5 %) individuals had stable SCD, 195 (43.1 %) unstable SCD and 174 (38.4 %) never reported SCD. Stable SCD was associated with increased risk of progression to MCI and dementia (unadjusted HR = 1.8, 95 % CI = 1.2-2.6; p < .01), whereas unstable SCD yielded a decreased progression risk (unadjusted HR = 0.5, 95 % CI = 0.4-0.7; p < .001) compared to no SCD. When adjusted for baseline cognitive functioning, progression risk in individuals with stable SCD was significantly increased in comparison to individuals with unstable SCD, but not compared to individuals without SCD. CONCLUSIONS: Our results, though preliminary, suggest that stable SCD, i.e., repeated reports of SCD, may yield an increased risk of progression to MCI and dementia compared to unstable SCD. Baseline cognitive scores, though within a normal range, seem to be a driver of progression in stable SCD. Future research is warranted to investigate whether stability could hold as a SCD research feature.

Authors: S. Roehr, A. Villringer, M. C. Angermeyer, T. Luck, S. G. Riedel-Heller

Date Published: 4th Nov 2016

Publication Type: Journal article

Human Diseases: dementia, Alzheimer's disease

Abstract (Expand)

BACKGROUND The purpose of this study was to estimate precise age-specific tubo-ovarian carcinoma (TOC) and breast cancer (BC) risks for carriers of pathogenic variants in RAD51C and RAD51D. METHODS We We analysed data from 6178 families, 125 with pathogenic variants in RAD51C; and 6690 families, 60 with pathogenic variants in RAD51D. TOC and BC relative and cumulative risks were estimated using complex segregation analysis to model the cancer inheritance patterns in families, while adjusting for the mode of ascertainment of each family. All statistical tests were two-sided. RESULTS Pathogenic variants in both RAD51C and RAD51D were associated with TOC (RAD51C RR = 7.55, 95%CI:5.60-10.19, p = 5 \times 10-40; RAD51D RR = 7.60, 95%CI:5.61-10.30, p = 5 \times 10-39) and BC (RAD51C RR = 1.99, 95%CI:1.39-2.85, p = 1.55 \times 10-4; RAD51D RR = 1.83, 95%CI:1.24-2.72, p = 0.002). For both RAD51C and RAD51D, there was a suggestion that the TOC RRs increased with age until around age 60 years and decreased thereafter. The estimated cumulative risks of developing TOC to age 80 were 11% (95%CI:6-21%) for RAD51C and 13% (95%CI:7-23%) for RAD51D pathogenic variant carriers. The estimated cumulative risks of developing BC to 80 were 21% (95%CI:15-29%) for RAD51C and 20% (95%CI:14-28%) for RAD51D pathogenic variant carriers. Both TOC and BC risks for RAD51C/D pathogenic variant carriers varied by cancer family history, and could be as high as 32-36% for TOC, for carriers with two first degree relatives diagnosed with TOC; or 44-46% for BC, for carriers with two first degree relatives diagnosed with BC. CONCLUSIONS These estimates will facilitate the genetic counselling of RAD51C and RAD51D pathogenic variant carriers and justify the incorporation of RAD51C and RAD51D into cancer risk prediction models.

Authors: Xin Yang, Honglin Song, Goska Leslie, Christoph Engel, Eric Hahnen, Bernd Auber, Judit Horváth, Karin Kast, Dieter Niederacher, Clare Turnbull, Richard Houlston, Helen Hanson, Chey Loveday, Jill S. Dolinsky, Holly Laduca, Susan J. Ramus, Usha Menon, Adam N. Rosenthal, Ian Jacobs, Simon A. Gayther, Ed Dicks, Heli Nevanlinna, Kristiina Aittomäki, Liisa M. Pelttari, Hans Ehrencrona, Åke Borg, Anders Kvist, Barbara Rivera, Thomas v. O. Hansen, Malene Djursby, Andrew Lee, Joe Dennis, David D. Bowtell, Nadia Traficante, Orland Diez, Judith Balmaña, Stephen B. Gruber, Georgia Chenevix-Trench, Allan Jensen, Susanne K. Kjær, Estrid Høgdall, Laurent Castéra, Judy Garber, Ramunas Janavicius, Ana Osorio, Lisa Golmard, Ana Vega, Fergus J. Couch, Mark Robson, Jacek Gronwald, Susan M. Domchek, Julie O. Culver, Miguel de La Hoya, Douglas F. Easton, William D. Foulkes, Marc Tischkowitz, Alfons Meindl, Rita K. Schmutzler, Paul D. P. Pharoah, Antonis C. Antoniou

Date Published: 28th Feb 2020

Publication Type: Journal article

Human Diseases: hereditary breast ovarian cancer syndrome

Abstract (Expand)

Germline mutations in BRCA1 and BRCA2 are associated with increased risks of breast and ovarian cancer. A genome-wide association study (GWAS) identified six alleles associated with risk of ovarian cancer for women in the general population. We evaluated four of these loci as potential modifiers of ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Four single-nucleotide polymorphisms (SNPs), rs10088218 (at 8q24), rs2665390 (at 3q25), rs717852 (at 2q31), and rs9303542 (at 17q21), were genotyped in 12,599 BRCA1 and 7,132 BRCA2 carriers, including 2,678 ovarian cancer cases. Associations were evaluated within a retrospective cohort approach. All four loci were associated with ovarian cancer risk in BRCA2 carriers; rs10088218 per-allele hazard ratio (HR) = 0.81 (95% CI: 0.67-0.98) P-trend = 0.033, rs2665390 HR = 1.48 (95% CI: 1.21-1.83) P-trend = 1.8 \times 10(-4), rs717852 HR = 1.25 (95% CI: 1.10-1.42) P-trend = 6.6 \times 10(-4), rs9303542 HR = 1.16 (95% CI: 1.02-1.33) P-trend = 0.026. Two loci were associated with ovarian cancer risk in BRCA1 carriers; rs10088218 per-allele HR = 0.89 (95% CI: 0.81-0.99) P-trend = 0.029, rs2665390 HR = 1.25 (95% CI: 1.10-1.42) P-trend = 6.1 \times 10(-4). The HR estimates for the remaining loci were consistent with odds ratio estimates for the general population. The identification of multiple loci modifying ovarian cancer risk may be useful for counseling women with BRCA1 and BRCA2 mutations regarding their risk of ovarian cancer.

Authors: Susan J. Ramus, Antonis C. Antoniou, Karoline B. Kuchenbaecker, Penny Soucy, Jonathan Beesley, Xiaoqing Chen, Lesley McGuffog, Olga M. Sinilnikova, Sue Healey, Daniel Barrowdale, Andrew Lee, Mads Thomassen, Anne-Marie Gerdes, Torben A. Kruse, Uffe Birk Jensen, Anne-Bine Skytte, Maria A. Caligo, Annelie Liljegren, Annika Lindblom, Håkan Olsson, Ulf Kristoffersson, Marie Stenmark-Askmalm, Beatrice Melin, Susan M. Domchek, Katherine L. Nathanson, Timothy R. Rebbeck, Anna Jakubowska, Jan Lubinski, Katarzyna Jaworska, Katarzyna Durda, Elżbieta Złowocka, Jacek Gronwald, Tomasz Huzarski, Tomasz Byrski, Cezary Cybulski, Aleksandra Toloczko-Grabarek, Ana Osorio, Javier Benitez, Mercedes Duran, Maria-Isabel Tejada, Ute Hamann, Matti Rookus, Flora E. van Leeuwen, Cora M. Aalfs, Hanne E. J. Meijers-Heijboer, Christi J. van Asperen, K. E. P. van Roozendaal, Nicoline Hoogerbrugge, J. Margriet Collée, Mieke Kriege, Rob B. van der Luijt, Susan Peock, Debra Frost, Steve D. Ellis, Radka Platte, Elena Fineberg, D. Gareth Evans, Fiona Lalloo, Chris Jacobs, Ros Eeles, Julian Adlard, Rosemarie Davidson, Diana Eccles, Trevor Cole, Jackie Cook, Joan Paterson, Fiona Douglas, Carole Brewer, Shirley Hodgson, Patrick J. Morrison, Lisa Walker, Mary E. Porteous, M. John Kennedy, Harsh Pathak, Andrew K. Godwin, Dominique Stoppa-Lyonnet, Virginie Caux-Moncoutier, Antoine de Pauw, Marion Gauthier-Villars, Sylvie Mazoyer, Mélanie Léoné, Alain Calender, Christine Lasset, Valérie Bonadona, Agnès Hardouin, Pascaline Berthet, Yves-Jean Bignon, Nancy Uhrhammer, Laurence Faivre, Catherine Loustalot, Saundra Buys, Mary Daly, Alex Miron, Mary Beth Terry, Wendy K. Chung, Esther M. John, Melissa Southey, David Goldgar, Christian F. Singer, Muy-Kheng Tea, Georg Pfeiler, Anneliese Fink-Retter, Thomas v. O. Hansen, Bent Ejlertsen, Oskar Th Johannsson, Kenneth Offit, Tomas Kirchhoff, Mia M. Gaudet, Joseph Vijai, Mark Robson, Marion Piedmonte, Kelly-Anne Phillips, Linda van Le, James S. Hoffman, Amanda Ewart Toland, Marco Montagna, Silvia Tognazzo, Evgeny Imyanitov, Claudine Issacs, Ramunas Janavicius, Conxi Lazaro, Iganacio Blanco, Eva Tornero, Matilde Navarro, Kirsten B. Moysich, Beth Y. Karlan, Jenny Gross, Edith Olah, Tibor Vaszko, Soo-Hwang Teo, Patricia A. Ganz, Mary S. Beattie, Cecelia M. Dorfling, Elizabeth J. van Rensburg, Orland Diez, Ava Kwong, Rita K. Schmutzler, Barbara Wappenschmidt, Christoph Engel, Alfons Meindl, Nina Ditsch, Norbert Arnold, Simone Heidemann, Dieter Niederacher, Sabine Preisler-Adams, Dorotehea Gadzicki, Raymonda Varon-Mateeva, Helmut Deissler, Andrea Gehrig, Christian Sutter, Karin Kast, Britta Fiebig, Dieter Schäfer, Trinidad Caldes, Miguel de La Hoya, Heli Nevanlinna, Kristiina Aittomäki, Marie Plante, Amanda B. Spurdle, Susan L. Neuhausen, Yuan Chun Ding, Xianshu Wang, Noralane Lindor, Zachary Fredericksen, V. Shane Pankratz, Paolo Peterlongo, Siranoush Manoukian, Bernard Peissel, Daniela Zaffaroni, Bernardo Bonanni, Loris Bernard, Riccardo Dolcetti, Laura Papi, Laura Ottini, Paolo Radice, Mark H. Greene, Phuong L. Mai, Irene L. Andrulis, Gord Glendon, Hilmi Ozcelik, Paul D. P. Pharoah, Simon A. Gayther, Jacques Simard, Douglas F. Easton, Fergus J. Couch, Georgia Chenevix-Trench

Date Published: 1st Apr 2012

Publication Type: Journal article

Human Diseases: hereditary breast ovarian cancer syndrome

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