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2. Levels of Alzheimer's disease blood biomarkers are altered after food intake—A pilot intervention study in healthy adults.

Author

Huber, Hanna, Ashton, Nicholas J., Schieren, Alina, Montoliu‐Gaya, Laia, Molfetta, Guglielmo Di, Brum, Wagner S., Lantero‐Rodriguez, Juan, Grötschel, Lana, Stoffel‐Wagner, Birgit, Coenen, Martin, Weinhold, Leonie, Schmid, Matthias, Blennow, Kaj, Stehle, Peter, Zetterberg, Henrik, and Simon, Marie‐Christine

Abstract

INTRODUCTION: Blood biomarkers accurately identify Alzheimer's disease (AD) pathophysiology and axonal injury. We investigated the influence of food intake on AD‐related biomarkers in cognitively healthy, obese adults at high metabolic risk. METHODS: One‐hundred eleven participants underwent repeated blood sampling during 3 h after a standardized meal (postprandial group, PG). For comparison, blood was sampled from a fasting subgroup over 3 h (fasting group, FG). Plasma neurofilament light (NfL), glial fibrillary acidic protein (GFAP), amyloid‐beta (Aβ) 42/40, phosphorylated tau (p‐tau) 181 and 231, and total‐tau were measured via single molecule array assays. RESULTS: Significant differences were found for NfL, GFAP, Aβ42/40, p‐tau181, and p‐tau231 between FG and PG. The greatest change to baseline occurred for GFAP and p‐tau181 (120 min postprandially, p < 0.0001). CONCLUSION: Our data suggest that AD‐related biomarkers are altered by food intake. Further studies are needed to verify whether blood biomarker sampling should be performed in the fasting state. Highlights: Acute food intake alters plasma biomarkers of Alzheimer's disease in obese, otherwise healthy adults.We also found dynamic fluctuations in plasma biomarkers concentration in the fasting state suggesting physiological diurnal variations.Further investigations are highly needed to verify if biomarker measurements should be performed in the fasting state and at a standardized time of day to improve the diagnostic accuracy. [ABSTRACT FROM AUTHOR]

Published
2023
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5. Generative Pre-trained Transformer 4 makes cardiovascular magnetic resonance reports easy to understand

Author

Salam, Babak, Kravchenko, Dmitrij, Nowak, Sebastian, Sprinkart, Alois M., Weinhold, Leonie, Odenthal, Anna, Mesropyan, Narine, Bischoff, Leon M., Attenberger, Ulrike, Kuetting, Daniel L., Luetkens, Julian A., and Isaak, Alexander

Abstract

Patients are increasingly using Generative Pre-trained Transformer 4 (GPT-4) to better understand their own radiology findings.

Published
2024
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6. New insights into the genetic etiology of Alzheimer’s disease and related dementias

Author

Bellenguez, Céline, Küçükali, Fahri, Jansen, Iris E., Kleineidam, Luca, Moreno-Grau, Sonia, Amin, Najaf, Naj, Adam C., Campos-Martin, Rafael, Grenier-Boley, Benjamin, Andrade, Victor, Holmans, Peter A., Boland, Anne, Damotte, Vincent, van der Lee, Sven J., Costa, Marcos R., Kuulasmaa, Teemu, Yang, Qiong, de Rojas, Itziar, Bis, Joshua C., Yaqub, Amber, Prokic, Ivana, Chapuis, Julien, Ahmad, Shahzad, Giedraitis, Vilmantas, Aarsland, Dag, Garcia-Gonzalez, Pablo, Abdelnour, Carla, Alarcón-Martín, Emilio, Alcolea, Daniel, Alegret, Montserrat, Alvarez, Ignacio, Álvarez, Victoria, Armstrong, Nicola J., Tsolaki, Anthoula, Antúnez, Carmen, Appollonio, Ildebrando, Arcaro, Marina, Archetti, Silvana, Pastor, Alfonso Arias, Arosio, Beatrice, Athanasiu, Lavinia, Bailly, Henri, Banaj, Nerisa, Baquero, Miquel, Barral, Sandra, Beiser, Alexa, Pastor, Ana Belén, Below, Jennifer E., Benchek, Penelope, Benussi, Luisa, Berr, Claudine, Besse, Céline, Bessi, Valentina, Binetti, Giuliano, Bizarro, Alessandra, Blesa, Rafael, Boada, Mercè, Boerwinkle, Eric, Borroni, Barbara, Boschi, Silvia, Bossù, Paola, Bråthen, Geir, Bressler, Jan, Bresner, Catherine, Brodaty, Henry, Brookes, Keeley J., Brusco, Luis Ignacio, Buiza-Rueda, Dolores, Bûrger, Katharina, Burholt, Vanessa, Bush, William S., Calero, Miguel, Cantwell, Laura B., Chene, Geneviève, Chung, Jaeyoon, Cuccaro, Michael L., Carracedo, Ángel, Cecchetti, Roberta, Cervera-Carles, Laura, Charbonnier, Camille, Chen, Hung-Hsin, Chillotti, Caterina, Ciccone, Simona, Claassen, Jurgen A. H. R., Clark, Christopher, Conti, Elisa, Corma-Gómez, Anaïs, Costantini, Emanuele, Custodero, Carlo, Daian, Delphine, Dalmasso, Maria Carolina, Daniele, Antonio, Dardiotis, Efthimios, Dartigues, Jean-François, de Deyn, Peter Paul, de Paiva Lopes, Katia, de Witte, Lot D., Debette, Stéphanie, Deckert, Jürgen, del Ser, Teodoro, Denning, Nicola, DeStefano, Anita, Dichgans, Martin, Diehl-Schmid, Janine, Diez-Fairen, Mónica, Rossi, Paolo Dionigi, Djurovic, Srdjan, Duron, Emmanuelle, Düzel, Emrah, Dufouil, Carole, Eiriksdottir, Gudny, Engelborghs, Sebastiaan, Escott-Price, Valentina, Espinosa, Ana, Ewers, Michael, Faber, Kelley M., Fabrizio, Tagliavini, Nielsen, Sune Fallgaard, Fardo, David W., Farotti, Lucia, Fenoglio, Chiara, Fernández-Fuertes, Marta, Ferrari, Raffaele, Ferreira, Catarina B., Ferri, Evelyn, Fin, Bertrand, Fischer, Peter, Fladby, Tormod, Fließbach, Klaus, Fongang, Bernard, Fornage, Myriam, Fortea, Juan, Foroud, Tatiana M., Fostinelli, Silvia, Fox, Nick C., Franco-Macías, Emlio, Bullido, María J., Frank-García, Ana, Froelich, Lutz, Fulton-Howard, Brian, Galimberti, Daniela, García-Alberca, Jose Maria, García-González, Pablo, Garcia-Madrona, Sebastian, Garcia-Ribas, Guillermo, Ghidoni, Roberta, Giegling, Ina, Giorgio, Giaccone, Goate, Alison M., Goldhardt, Oliver, Gomez-Fonseca, Duber, González-Pérez, Antonio, Graff, Caroline, Grande, Giulia, Green, Emma, Grimmer, Timo, Grünblatt, Edna, Grunin, Michelle, Gudnason, Vilmundur, Guetta-Baranes, Tamar, Haapasalo, Annakaisa, Hadjigeorgiou, Georgios, Haines, Jonathan L., Hamilton-Nelson, Kara L., Hampel, Harald, Hanon, Olivier, Hardy, John, Hartmann, Annette M., Hausner, Lucrezia, Harwood, Janet, Heilmann-Heimbach, Stefanie, Helisalmi, Seppo, Heneka, Michael T., Hernández, Isabel, Herrmann, Martin J., Hoffmann, Per, Holmes, Clive, Holstege, Henne, Vilas, Raquel Huerto, Hulsman, Marc, Humphrey, Jack, Biessels, Geert Jan, Jian, Xueqiu, Johansson, Charlotte, Jun, Gyungah R., Kastumata, Yuriko, Kauwe, John, Kehoe, Patrick G., Kilander, Lena, Ståhlbom, Anne Kinhult, Kivipelto, Miia, Koivisto, Anne, Kornhuber, Johannes, Kosmidis, Mary H., Kukull, Walter A., Kuksa, Pavel P., Kunkle, Brian W., Kuzma, Amanda B., Lage, Carmen, Laukka, Erika J., Launer, Lenore, Lauria, Alessandra, Lee, Chien-Yueh, Lehtisalo, Jenni, Lerch, Ondrej, Lleó, Alberto, Longstreth, William, Lopez, Oscar, de Munain, Adolfo Lopez, Love, Seth, Löwemark, Malin, Luckcuck, Lauren, Lunetta, Kathryn L., Ma, Yiyi, Macías, Juan, MacLeod, Catherine A., Maier, Wolfgang, Mangialasche, Francesca, Spallazzi, Marco, Marquié, Marta, Marshall, Rachel, Martin, Eden R., Montes, Angel Martín, Rodríguez, Carmen Martínez, Masullo, Carlo, Mayeux, Richard, Mead, Simon, Mecocci, Patrizia, Medina, Miguel, Meggy, Alun, Mehrabian, Shima, Mendoza, Silvia, Menéndez-González, Manuel, Mir, Pablo, Moebus, Susanne, Mol, Merel, Molina-Porcel, Laura, Montrreal, Laura, Morelli, Laura, Moreno, Fermin, Morgan, Kevin, Mosley, Thomas, Nöthen, Markus M., Muchnik, Carolina, Mukherjee, Shubhabrata, Nacmias, Benedetta, Ngandu, Tiia, Nicolas, Gael, Nordestgaard, Børge G., Olaso, Robert, Orellana, Adelina, Orsini, Michela, Ortega, Gemma, Padovani, Alessandro, Paolo, Caffarra, Papenberg, Goran, Parnetti, Lucilla, Pasquier, Florence, Pastor, Pau, Peloso, Gina, Pérez-Cordón, Alba, Pérez-Tur, Jordi, Pericard, Pierre, Peters, Oliver, Pijnenburg, Yolande A. L., Pineda, Juan A., Piñol-Ripoll, Gerard, Pisanu, Claudia, Polak, Thomas, Popp, Julius, Posthuma, Danielle, Priller, Josef, Puerta, Raquel, Quenez, Olivier, Quintela, Inés, Thomassen, Jesper Qvist, Rábano, Alberto, Rainero, Innocenzo, Rajabli, Farid, Ramakers, Inez, Real, Luis M., Reinders, Marcel J. T., Reitz, Christiane, Reyes-Dumeyer, Dolly, Ridge, Perry, Riedel-Heller, Steffi, Riederer, Peter, Roberto, Natalia, Rodriguez-Rodriguez, Eloy, Rongve, Arvid, Allende, Irene Rosas, Rosende-Roca, Maitée, Royo, Jose Luis, Rubino, Elisa, Rujescu, Dan, Sáez, María Eugenia, Sakka, Paraskevi, Saltvedt, Ingvild, Sanabria, Ángela, Sánchez-Arjona, María Bernal, Sanchez-Garcia, Florentino, Juan, Pascual Sánchez, Sánchez-Valle, Raquel, Sando, Sigrid B., Sarnowski, Chloé, Satizabal, Claudia L., Scamosci, Michela, Scarmeas, Nikolaos, Scarpini, Elio, Scheltens, Philip, Scherbaum, Norbert, Scherer, Martin, Schmid, Matthias, Schneider, Anja, Schott, Jonathan M., Selbæk, Geir, Seripa, Davide, Serrano, Manuel, Sha, Jin, Shadrin, Alexey A., Skrobot, Olivia, Slifer, Susan, Snijders, Gijsje J. L., Soininen, Hilkka, Solfrizzi, Vincenzo, Solomon, Alina, Song, Yeunjoo, Sorbi, Sandro, Sotolongo-Grau, Oscar, Spalletta, Gianfranco, Spottke, Annika, Squassina, Alessio, Stordal, Eystein, Tartan, Juan Pablo, Tárraga, Lluís, Tesí, Niccolo, Thalamuthu, Anbupalam, Thomas, Tegos, Tosto, Giuseppe, Traykov, Latchezar, Tremolizzo, Lucio, Tybjærg-Hansen, Anne, Uitterlinden, Andre, Ullgren, Abbe, Ulstein, Ingun, Valero, Sergi, Valladares, Otto, Broeckhoven, Christine Van, Vance, Jeffery, Vardarajan, Badri N., van der Lugt, Aad, Dongen, Jasper Van, van Rooij, Jeroen, van Swieten, John, Vandenberghe, Rik, Verhey, Frans, Vidal, Jean-Sébastien, Vogelgsang, Jonathan, Vyhnalek, Martin, Wagner, Michael, Wallon, David, Wang, Li-San, Wang, Ruiqi, Weinhold, Leonie, Wiltfang, Jens, Windle, Gill, Woods, Bob, Yannakoulia, Mary, Zare, Habil, Zhao, Yi, Zhang, Xiaoling, Zhu, Congcong, Zulaica, Miren, Farrer, Lindsay A., Psaty, Bruce M., Ghanbari, Mohsen, Raj, Towfique, Sachdev, Perminder, Mather, Karen, Jessen, Frank, Ikram, M. Arfan, de Mendonça, Alexandre, Hort, Jakub, Tsolaki, Magda, Pericak-Vance, Margaret A., Amouyel, Philippe, Williams, Julie, Frikke-Schmidt, Ruth, Clarimon, Jordi, Deleuze, Jean-François, Rossi, Giacomina, Seshadri, Sudha, Andreassen, Ole A., Ingelsson, Martin, Hiltunen, Mikko, Sleegers, Kristel, Schellenberg, Gerard D., van Duijn, Cornelia M., Sims, Rebecca, van der Flier, Wiesje M., Ruiz, Agustín, Ramirez, Alfredo, and Lambert, Jean-Charles

Abstract

Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOEε4 allele.

Published
2022
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7. P‐tau217 is the earliest plasma marker of dementia of the Alzheimer's type in older primary care patients.

Author

Kleineidam, Luca, Oezdemir, Selçuk, Martino‐Adami, Pamela, Weinhold, Leonie, Koehler, David, Chatterjee, Madhurima, Pentzek, Michael, Weyerer, Siegfried, Bickel, Horst, Wiese, Birgitt, Riedel‐Heller, Steffi G., Scherer, Martin, Blennow, Kaj, Zetterberg, Henrik, Schmid, Matthias, Ruiz, Agustin, Peters, Oliver, Jeromin, Andreas, Wagner, Michael, and Ramirez, Alfredo

Abstract

Background: Blood‐based biomarkers of Alzheimer's disease (AD) may provide an avenue for early identification of individuals at risk for AD dementia, which is a crucial task for implementing upcoming disease‐modifying therapies in clinical practice. Among blood‐based biomarkers, P‐tau217 has shown a particular sensitivity to amyloid pathology and utility for differential diagnosis of AD. However, less is known about the association of P‐tau217 with dementia risk in older primary care patients. Method: To address this question in an extreme phenotype design, we measured plasma P‐tau217 using the validated ALZPath pTau217 assay developed on the Single molecule array (Simoa) technology in 184 patients (median age = 83 years) free of dementia at blood draw who converted to clinically diagnosed dementia of the Alzheimer's type (DAT) during up to eight years of follow‐up. Furthermore, P‐tau217 was measured in 184 age‐ and sex‐matched cognitively normal controls that stayed free of any cognitive impairment during follow‐up. All participants were derived from the primary care‐based AgeCoDe‐cohort. In addition, Aβ42/Aβ40, P‐tau181, NfL, and GFAP were quantified using Simoa technology. Associations between P‐tau217 and conversion to DAT were assessed using conditional logistic regression and compared to associations of conversion to DAT with Aβ42/Aβ40, P‐tau181, NfL, and GFAP. The influence of time to DAT diagnosis on the associations was assessed by generalized additive models. Result: P‐tau217 was strongly associated with conversion to DAT (ORper‐1SD‐increase [95%‐CI] = 10.29 [5.16‐20.41], p = 2.0*10−11, N = 368). This association was present irrespective of whether DAT‐converter showed MCI (ORper‐1SD‐increase [95%‐CI] = 3.49 [1.34‐9.12], p = 1.1*10−2) or no MCI (ORper‐1SD‐increase[95%‐CI] = 16.07[6.54‐39.71], p = 1.3*10−9) at blood draw. No other marker showed a similarly strong association with conversion (second‐best performance: GFAP; ORper‐1SD‐increase [95%‐CI] = 1.36 [1.19‐1.54], p = 2.15*10−2). Patients converting to DAT eight years after blood draw already presented with elevated P‐tau217 levels compared to their matched controls. Other markers (GFAP, P‐tau181) started to show differences in individuals converting to DAT four years after blood draw. Conclusion: P‐tau217 is the most sensitive plasma marker for risk of conversion to DAT in older patients from primary care patients in comparison to plasma P‐tau181, Aβ42/Aβ40, NfL, and GFAP. [ABSTRACT FROM AUTHOR]

Published
2023
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8. Surgical reconstruction of small and medium rotator cuff tears shows superior long-term results

Author

Wirth, Barbara, Weinhold, Leonie, and Müller-Rath, Ralf

Abstract

Background: Degenerative rotator cuff tears are common in elderly patients. However, the treatment strategies remain controversial. While physiotherapy can lead to pain relief and improved shoulder function, spontaneous tendon healing will not take place and, thus, non-operative management bears the risk of tear progression. Surgical management is the only way to restore the tendon-to-bone interface in spite of a considerable number of retears. Methods: The present study reviewed the data provided by randomized controlled trials (RCTs) that have compared physiotherapy with surgical rotator cuff repair. Systematic reviews of this kind have been published before; however, this paper re-analyzes the data, given that Moosmayer et al. recently published an RCT with 10-year follow-up. Such long-term data are comparatively rare in the field of musculoskeletal surgery and therefore a reconsideration of treatment recommendations seems necessary. Results: The results show a mean difference in the Constant and Murley score of 6.2 points (95% confidence interval, 2.6; 9.7, P&lt; 0.001) in favor of the surgical groups. The visual analog scale pain score also improved more in the operatively treated patients with a mean difference of −1.4 (95% confidence interval −2.1; −0.8, P&lt; 0.001). Conclusion: In summary, this review shows superior clinical results for surgical repair of small- to medium-sized degenerative rotator cuff tears especially in the long term compared to physiotherapy.

Published
2021
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9. Glucose intake is influencing the concentration of AD‐related plasma biomarkers in healthy adults.

Author

Grötschel, Lana, Huber, Hanna, Ashton, Nicholas J., Schieren, Alina, Weinhold, Leonie, Schmid, Matthias, Coenen, Martin, Blennow, Kaj, Stehle, Peter, Zetterberg, Henrik, and Simon, Marie‐Christine

Abstract

Background: Blood biomarker analyses are seen as a great aid to early diagnose and confirm underlying Alzheimer's disease (AD) pathology. Developing evidence suggests that certain confounders need to be considered which may affect the reliability of biomarker results, e.g., chronic kidney disease. However, little is known with respect to potential confounding effects of energy/nutrient intake on these biomarkers. Thus, we aim to study the short‐term effects of oral glucose intake in healthy, obese adults. Method: 111 participants (60±7y, BMI 31±4kg/m2, 47 males) ingested 300ml of a glucose syrup (75g glucose, Accu‐Chek, Roche). Neurofilament light, glial fibrillary acidic protein [GFAP], amyloid‐β 42/40 ratio, phosphorylated tau ([p‐tau] 181 and p‐tau 231) were measured in fasting (0 minutes) and postprandial blood samples collected 15, 30, 45, 60, 120 and 180 minutes after ingestion of the glucose syrup using ultra‐sensitive Single molecule array assays. Additionally, a fasting (control) group (n = 26) was followed over the same time period. Statistical analysis was done using polynomial spline of degree 3 to test for differences in parameter progression over time within and between groups. Result: In both groups, all biomarkers changed significantly over time (glucose group: all p<0.0001, fasting group all p<0.05) compared to baseline (0 minutes). The changes to baseline in GFAP were significantly different after glucose ingestion compared to the fasting state (p<0.0001). The GFAP level decreased in the early postprandial phase (until 60 minutes) and subsequently increased in the late postprandial phase. Conclusion: Our results suggest that plasma biomarkers for AD‐related pathologies are influenced by the individual nutritional status (prolonged fasting, postprandial situation). This should be considered when using AD‐related biomarkers for screening and diagnostic purposes. [ABSTRACT FROM AUTHOR]

Published
2023
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10. Plate fixation and tension band wiring after isolated olecranon fracture comparison of outcome and complications

Author

Gathen, Martin, Jaenisch, Max, Peez, Christian, Weinhold, Leonie, Schmid, Matthias, Welle, Kristian, Burger, Christof, and Kabir, Koroush

Abstract

Olecranon fractures are common injuries in patients of any age. The vast majority are treated with two operation techniques: a plate fixation (PF) or tension band wiring (TBW). The objective of this study is to compare the outcomes of surgically treated olecranon fractures with plate fixation or tension band wiring. We hypothesise that PF patients would show significantly inferior outcomes due to more complex injuries.

Published
2020
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11. Deep Learning Super-Resolution Reconstruction for Fast and Motion-Robust T2-weighted Prostate MRI

Author

Bischoff, Leon M., Peeters, Johannes M., Weinhold, Leonie, Krausewitz, Philipp, Ellinger, Jörg, Katemann, Christoph, Isaak, Alexander, Weber, Oliver M., Kuetting, Daniel, Attenberger, Ulrike, Pieper, Claus C., Sprinkart, Alois M., and Luetkens, Julian A.

Abstract

A deep learning reconstruction method for low-resolution prostate T2-weighted sequences reduced acquisition times and improved image quality compared with standard acquisitions while achieving excellent Prostate Imaging Reporting and Data System score agreement with conventional images.

Published
2023
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13. Lymphocyte transformation test for drug allergy detection

Author

Glässner, Andreas, Dubrall, Diana, Weinhold, Leonie, Schmid, Matthias, and Sachs, Bernhardt

Abstract

The lymphocyte transformation test (LTT) is an in vitro test system for the detection of a sensitization in the context of allergies to drugs. Its reported sensitivity varies largely and seems to be affected by different parameters. In review articles, the average LTT performance was often calculated by combining overall mean sensitivities of various published studies, but without considering different patient characteristics or varying patient numbers per publication.

Published
2022
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