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1. Next-generation phenotyping integrated in a national framework for patients with ultrarare disorders improves genetic diagnostics and yields new molecular findings

Author

Schmidt, Axel, Danyel, Magdalena, Grundmann, Kathrin, Brunet, Theresa, Klinkhammer, Hannah, Hsieh, Tzung-Chien, Engels, Hartmut, Peters, Sophia, Knaus, Alexej, Moosa, Shahida, Averdunk, Luisa, Boschann, Felix, Sczakiel, Henrike Lisa, Schwartzmann, Sarina, Mensah, Martin Atta, Pantel, Jean Tori, Holtgrewe, Manuel, Bösch, Annemarie, Weiß, Claudia, Weinhold, Natalie, Suter, Aude-Annick, Stoltenburg, Corinna, Neugebauer, Julia, Kallinich, Tillmann, Kaindl, Angela M., Holzhauer, Susanne, Bührer, Christoph, Bufler, Philip, Kornak, Uwe, Ott, Claus-Eric, Schülke, Markus, Nguyen, Hoa Huu Phuc, Hoffjan, Sabine, Grasemann, Corinna, Rothoeft, Tobias, Brinkmann, Folke, Matar, Nora, Sivalingam, Sugirthan, Perne, Claudia, Mangold, Elisabeth, Kreiss, Martina, Cremer, Kirsten, Betz, Regina C., Mücke, Martin, Grigull, Lorenz, Klockgether, Thomas, Spier, Isabel, Heimbach, André, Bender, Tim, Brand, Fabian, Stieber, Christiane, Morawiec, Alexandra Marzena, Karakostas, Pantelis, Schäfer, Valentin S., Bernsen, Sarah, Weydt, Patrick, Castro-Gomez, Sergio, Aziz, Ahmad, Grobe-Einsler, Marcus, Kimmich, Okka, Kobeleva, Xenia, Önder, Demet, Lesmann, Hellen, Kumar, Sheetal, Tacik, Pawel, Basin, Meghna Ahuja, Incardona, Pietro, Lee-Kirsch, Min Ae, Berner, Reinhard, Schuetz, Catharina, Körholz, Julia, Kretschmer, Tanita, Di Donato, Nataliya, Schröck, Evelin, Heinen, André, Reuner, Ulrike, Hanßke, Amalia-Mihaela, Kaiser, Frank J., Manka, Eva, Munteanu, Martin, Kuechler, Alma, Cordula, Kiewert, Hirtz, Raphael, Schlapakow, Elena, Schlein, Christian, Lisfeld, Jasmin, Kubisch, Christian, Herget, Theresia, Hempel, Maja, Weiler-Normann, Christina, Ullrich, Kurt, Schramm, Christoph, Rudolph, Cornelia, Rillig, Franziska, Groffmann, Maximilian, Muntau, Ania, Tibelius, Alexandra, Schwaibold, Eva M. C., Schaaf, Christian P., Zawada, Michal, Kaufmann, Lilian, Hinderhofer, Katrin, Okun, Pamela M., Kotzaeridou, Urania, Hoffmann, Georg F., Choukair, Daniela, Bettendorf, Markus, Spielmann, Malte, Ripke, Annekatrin, Pauly, Martje, Münchau, Alexander, Lohmann, Katja, Hüning, Irina, Hanker, Britta, Bäumer, Tobias, Herzog, Rebecca, Hellenbroich, Yorck, Westphal, Dominik S., Strom, Tim, Kovacs, Reka, Riedhammer, Korbinian M., Mayerhanser, Katharina, Graf, Elisabeth, Brugger, Melanie, Hoefele, Julia, Oexle, Konrad, Mirza-Schreiber, Nazanin, Berutti, Riccardo, Schatz, Ulrich, Krenn, Martin, Makowski, Christine, Weigand, Heike, Schröder, Sebastian, Rohlfs, Meino, Vill, Katharina, Hauck, Fabian, Borggraefe, Ingo, Müller-Felber, Wolfgang, Kurth, Ingo, Elbracht, Miriam, Knopp, Cordula, Begemann, Matthias, Kraft, Florian, Lemke, Johannes R., Hentschel, Julia, Platzer, Konrad, Strehlow, Vincent, Abou Jamra, Rami, Kehrer, Martin, Demidov, German, Beck-Wödl, Stefanie, Graessner, Holm, Sturm, Marc, Zeltner, Lena, Schöls, Ludger J., Magg, Janine, Bevot, Andrea, Kehrer, Christiane, Kaiser, Nadja, Turro, Ernest, Horn, Denise, Grüters-Kieslich, Annette, Klein, Christoph, Mundlos, Stefan, Nöthen, Markus, Riess, Olaf, Meitinger, Thomas, Krude, Heiko, Krawitz, Peter M., Haack, Tobias, Ehmke, Nadja, and Wagner, Matias

Published
2024
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2. Plasma extracellular vesicle tau and TDP-43 as diagnostic biomarkers in FTD and ALS

Author

Chatterjee, Madhurima, Özdemir, Selcuk, Fritz, Christian, Möbius, Wiebke, Kleineidam, Luca, Mandelkow, Eckhard, Biernat, Jacek, Doğdu, Cem, Peters, Oliver, Cosma, Nicoleta Carmen, Wang, Xiao, Schneider, Luisa-Sophia, Priller, Josef, Spruth, Eike, Kühn, Andrea A., Krause, Patricia, Klockgether, Thomas, Vogt, Ina R., Kimmich, Okka, Spottke, Annika, Hoffmann, Daniel C., Fliessbach, Klaus, Miklitz, Carolin, McCormick, Cornelia, Weydt, Patrick, Falkenburger, Björn, Brandt, Moritz, Guenther, René, Dinter, Elisabeth, Wiltfang, Jens, Hansen, Niels, Bähr, Mathias, Zerr, Inga, Flöel, Agnes, Nestor, Peter J., Düzel, Emrah, Glanz, Wenzel, Incesoy, Enise, Bürger, Katharina, Janowitz, Daniel, Perneczky, Robert, Rauchmann, Boris S., Hopfner, Franziska, Wagemann, Olivia, Levin, Johannes, Teipel, Stefan, Kilimann, Ingo, Goerss, Doreen, Prudlo, Johannes, Gasser, Thomas, Brockmann, Kathrin, Mengel, David, Zimmermann, Milan, Synofzik, Matthis, Wilke, Carlo, Selma-González, Judit, Turon-Sans, Janina, Santos-Santos, Miguel Angel, Alcolea, Daniel, Rubio-Guerra, Sara, Fortea, Juan, Carbayo, Álvaro, Lleó, Alberto, Rojas-García, Ricardo, Illán-Gala, Ignacio, Wagner, Michael, Frommann, Ingo, Roeske, Sandra, Bertram, Lucas, Heneka, Michael T., Brosseron, Frederic, Ramirez, Alfredo, Schmid, Matthias, Beschorner, Rudi, Halle, Annett, Herms, Jochen, Neumann, Manuela, Barthélemy, Nicolas R., Bateman, Randall J., Rizzu, Patrizia, Heutink, Peter, Dols-Icardo, Oriol, Höglinger, Günter, Hermann, Andreas, and Schneider, Anja

Published
2024
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3. Perivascular space enlargement accelerates in ageing and Alzheimer’s disease pathology: evidence from a three-year longitudinal multicentre study

Author

Menze, Inga, Bernal, Jose, Kaya, Pinar, Aki, Çağla, Pfister, Malte, Geisendörfer, Jonas, Yakupov, Renat, Coello, Roberto Duarte, Valdés-Hernández, Maria d. C., Heneka, Michael T., Brosseron, Frederic, Schmid, Matthias C., Glanz, Wenzel, Incesoy, Enise I., Butryn, Michaela, Rostamzadeh, Ayda, Meiberth, Dix, Peters, Oliver, Preis, Lukas, Lammerding, Dominik, Gref, Daria, Priller, Josef, Spruth, Eike J., Altenstein, Slawek, Lohse, Andrea, Hetzer, Stefan, Schneider, Anja, Fliessbach, Klaus, Kimmich, Okka, Vogt, Ina R., Wiltfang, Jens, Bartels, Claudia, Schott, Björn H., Hansen, Niels, Dechent, Peter, Buerger, Katharina, Janowitz, Daniel, Perneczky, Robert, Rauchmann, Boris-Stephan, Teipel, Stefan, Kilimann, Ingo, Goerss, Doreen, Laske, Christoph, Munk, Matthias H., Sanzenbacher, Carolin, Hinderer, Petra, Scheffler, Klaus, Spottke, Annika, Roy-Kluth, Nina, Lüsebrink, Falk, Neumann, Katja, Wardlaw, Joanna, Jessen, Frank, Schreiber, Stefanie, Düzel, Emrah, and Ziegler, Gabriel

Published
2024
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4. The comorbidity profiles and medication issues of patients with multiple system atrophy: a systematic cross-sectional analysis

Author

Ye, Lan, Greten, Stephan, Wegner, Florian, Doll-Lee, Johanna, Krey, Lea, Heine, Johanne, Gandor, Florin, Vogel, Annemarie, Berger, Luise, Gruber, Doreen, Levin, Johannes, Katzdobler, Sabrina, Peters, Oliver, Dashti, Eman, Priller, Josef, Spruth, Eike Jakob, Kühn, Andrea A., Krause, Patricia, Spottke, Annika, Schneider, Anja, Beyle, Aline, Kimmich, Okka, Donix, Markus, Haussmann, Robert, Brandt, Moritz, Dinter, Elisabeth, Wiltfang, Jens, Schott, Björn H., Zerr, Inga, Bähr, Mathias, Buerger, Katharina, Janowitz, Daniel, Perneczky, Robert, Rauchmann, Boris-Stephan, Weidinger, Endy, Düzel, Emrah, Glanz, Wenzel, Teipel, Stefan, Kilimann, Ingo, Wurster, Isabel, Brockmann, Kathrin, Hoffmann, Daniel C., Klockgether, Thomas, Krause, Olaf, Heck, Johannes, Höglinger, Günter U., and Klietz, Martin

Published
2024
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5. The comorbidity and co-medication profile of patients with progressive supranuclear palsy

Author

Greten, Stephan, Wegner, Florian, Jensen, Ida, Krey, Lea, Rogozinski, Sophia, Fehring, Meret, Heine, Johanne, Doll-Lee, Johanna, Pötter-Nerger, Monika, Zeitzschel, Molly, Hagena, Keno, Pedrosa, David J., Eggers, Carsten, Bürk, Katrin, Trenkwalder, Claudia, Claus, Inga, Warnecke, Tobias, Süß, Patrick, Winkler, Jürgen, Gruber, Doreen, Gandor, Florin, Berg, Daniela, Paschen, Steffen, Classen, Joseph, Pinkhardt, Elmar H., Kassubek, Jan, Jost, Wolfgang H., Tönges, Lars, Kühn, Andrea A., Schwarz, Johannes, Peters, Oliver, Dashti, Eman, Priller, Josef, Spruth, Eike J., Krause, Patricia, Spottke, Annika, Schneider, Anja, Beyle, Aline, Kimmich, Okka, Donix, Markus, Haussmann, Robert, Brandt, Moritz, Dinter, Elisabeth, Wiltfang, Jens, Schott, Björn H., Zerr, Inga, Bähr, Mathias, Buerger, Katharina, Janowitz, Daniel, Perneczky, Robert, Rauchmann, Boris-Stephan, Weidinger, Endy, Levin, Johannes, Katzdobler, Sabrina, Düzel, Emrah, Glanz, Wenzel, Teipel, Stefan, Kilimann, Ingo, Prudlo, Johannes, Gasser, Thomas, Brockmann, Kathrin, Hoffmann, Daniel C., Klockgether, Thomas, Krause, Olaf, Heck, Johannes, Höglinger, Günter U., and Klietz, Martin

Published
2024
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6. The Progressive Supranuclear Palsy Clinical Deficits Scale

Author

Piot, Ines, Schweyer, Kerstin, Respondek, Gesine, Stamelou, Maria, Sckopke, Philipp, Schenk, Thomas, Goetz, Christopher G, Stebbins, Glenn T, Höglinger, Günter U, Gasser, Thomas, Hermann, Andreas, Höglinger, Günter, Höllerhage, Matthias, Kimmich, Okka, Klockgether, Thomas, Levin, Johannes, Machetanz, Gerrit, Osterrath, Antje, Palleis, Carla, Prudlo, Johannes, Spottke, Annika, Berg, Daniela, Bürk, Katrin, Claßen, Joseph, Eggers, Carsten, Greuel, Andrea, Grimm, Max‐Joseph, Hermann, Lennard, Iankova, Vassilena, Jahn, Klaus, Jost, Wolfgang, Klietz, Martin, Kühn, Andrea, Marxreiter, Franz, Paschen, Steffen, Poetter‐Nerger, Monika, Preisl, Marie‐Therese, Prilop, Lisa, Tönges, Lars, Trenkwalder, Claudia, Warnecke, Tobias, Wegner, Florian, Winkler, Jürgen, Antonini, Angelo, P, Kailash P, L, Adam L, Colosimo, Carlo, Compta, Yaroslau, Corvol, Jean‐Christophe, I, Lawrence I, E, Anthony E, Litvan, Irene, R, Huw R, Nilsson, Christer, and Pantelyat, Alexander

Subjects
Pediatric, Clinical Research, Perinatal Period - Conditions Originating in Perinatal Period, Neurosciences, Brain Disorders, 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis, Neurological, Disease Progression, Female, Fingers, Humans, Male, Motor Skills, Reproducibility of Results, Supranuclear Palsy, Progressive, progressive supranuclear palsy, clinical rating scales, outcome measures, power calculation, DescribePSP study group, ProPSP study group, MDS-endorsed PSP study group, Clinical Sciences, Human Movement and Sports Sciences, Neurology & Neurosurgery
Abstract

BackgroundThere is currently no undisputed, validated, clinically meaningful measure for deficits in the broad spectrum of PSP phenotypes.ObjectiveTo develop a scale to monitor clinical deficits in patients with PSP across its broad phenotypes.MethodsThe Progressive Supranuclear Palsy Clinical Deficits Scale was conceptualized to cover seven clinical domains (Akinesia-rigidity, Bradyphrenia, Communication, Dysphagia, Eye movements, Finger dexterity, and Gait & balance), each scored from 0 to 3 (no, mild, moderate, or severe deficits). User guidelines were developed to standardize its application. Progressive Supranuclear Palsy Clinical Deficits Scale scores were collected in patients fulfilling the MDS-PSP diagnostic criteria in two independent, multicenter, observational studies, both cross-sectionally (exploratory DescribePSP cohort; confirmatory ProPSP cohort) and longitudinally (12-months' follow-up, both cohorts).ResultsCognitive pretesting demonstrated easy scale utility. In total, 164 patients were scored (70.4 ± 7.6 years; 62% males, 35% variant phenotypes). Mean Progressive Supranuclear Palsy Clinical Deficits Scale completion time was 4 minutes. The Progressive Supranuclear Palsy Clinical Deficits Scale total score correlated with existing scales (e.g., Progressive Supranuclear Palsy Rating Scale: R = 0.88; P

Published
2020

7. Single-value brain activity scores reflect both severity and risk across the Alzheimer's continuum.

Author

Soch, Joram, Richter, Anni, Kizilirmak, Jasmin M, Schütze, Hartmut, Ziegler, Gabriel, Altenstein, Slawek, Brosseron, Frederic, Dechent, Peter, Fliessbach, Klaus, Freiesleben, Silka Dawn, Glanz, Wenzel, Gref, Daria, Heneka, Michael T, Hetzer, Stefan, Incesoy, Enise I, Kilimann, Ingo, Kimmich, Okka, Kleineidam, Luca, Kuhn, Elizabeth, and Laske, Christoph

Subjects
FUNCTIONAL magnetic resonance imaging, ALZHEIMER'S disease, DISEASE risk factors, PROGNOSIS, YOUNG adults
Abstract

Single-value scores reflecting the deviation from (FADE score) or similarity with (SAME score) prototypical novelty-related and memory-related functional MRI activation patterns in young adults have been proposed as imaging biomarkers of healthy neurocognitive ageing. Here, we tested the utility of these scores as potential diagnostic and prognostic markers in Alzheimer's disease (AD) and risk states like mild cognitive impairment (MCI) or subjective cognitive decline (SCD). To this end, we analysed subsequent memory functional MRI data from individuals with SCD, MCI and AD dementia as well as healthy controls and first-degree relatives of AD dementia patients (AD-rel) who participated in the multi-centre DELCODE study (n = 468). Based on the individual participants' whole-brain functional MRI novelty and subsequent memory responses, we calculated the FADE and SAME scores and assessed their association with AD risk stage, neuropsychological test scores, CSF amyloid positivity and APOE genotype. Memory-based FADE and SAME scores showed a considerably larger deviation from a reference sample of young adults in the MCI and AD dementia groups compared to healthy controls, SCD and AD-rel. In addition, novelty-based scores significantly differed between the MCI and AD dementia groups. Across the entire sample, single-value scores correlated with neuropsychological test performance. The novelty-based SAME score further differed between Aβ-positive and Aβ-negative individuals in SCD and AD-rel, and between ApoE ɛ4 carriers and non-carriers in AD-rel. Hence, FADE and SAME scores are associated with both cognitive performance and individual risk factors for AD. Their potential utility as diagnostic and prognostic biomarkers warrants further exploration, particularly in individuals with SCD and healthy relatives of AD dementia patients. [ABSTRACT FROM AUTHOR]

Published
2024
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8. Machine Learning-Based Perivascular Space Volumetry in Alzheimer Disease.

Author

Deike, Katerina, Decker, Andreas, Scheyhing, Paul, Harten, Julia, Zimmermann, Nadine, Paech, Daniel, Peters, Oliver, Freiesleben, Silka D., Schneider, Luisa-Sophie, Preis, Lukas, Priller, Josef, Spruth, Eike, Altenstein, Slawek, Lohse, Andrea, Fliessbach, Klaus, Kimmich, Okka, Wiltfang, Jens, Bartels, Claudia, Hansen, Niels, and Jessen, Frank

Published
2024
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9. Performance evaluation of automated white matter hyperintensity segmentation algorithms in a multicenter cohort on cognitive impairment and dementia

Author

Malo Gaubert, Andrea Dell’Orco, Catharina Lange, Antoine Garnier-Crussard, Isabella Zimmermann, Martin Dyrba, Marco Duering, Gabriel Ziegler, Oliver Peters, Lukas Preis, Josef Priller, Eike Jakob Spruth, Anja Schneider, Klaus Fliessbach, Jens Wiltfang, Björn H. Schott, Franziska Maier, Wenzel Glanz, Katharina Buerger, Daniel Janowitz, Robert Perneczky, Boris-Stephan Rauchmann, Stefan Teipel, Ingo Kilimann, Christoph Laske, Matthias H. Munk, Annika Spottke, Nina Roy, Laura Dobisch, Michael Ewers, Peter Dechent, John Dylan Haynes, Klaus Scheffler, Emrah Düzel, Frank Jessen, Miranka Wirth, for the DELCODE study group, Amthauer Holger, Cetindag Arda Can, Cosma Nicoleta Carmen, Diesing Dominik, Ehrlich Marie, Fenski Frederike, Freiesleben Silka Dawn, Fuentes Manuel, Hauser Dietmar, Hujer Nicole, Incesoy Enise Irem, Kainz Christian, Lange Catharina, Lindner Katja, Megges Herlind, Peters Oliver, Preis Lukas, Altenstein Slawek, Lohse Andrea, Franke Christiana, Priller Josef, Spruth Eike, Villar Munoz Irene, Barkhoff Miriam, Boecker Henning, Brosseron Frederic, Daamen Marcel, Engels Tanja, Faber Jennifer, Fließbach Klaus, Frommann Ingo, Grobe-Einsler Marcus, Hennes Guido, Herrmann Gabi, Jost Lorraine, Kalbhen Pascal, Kimmich Okka, Kobeleva Xenia, Kofler Barbara, McCormick Cornelia, Miebach Lisa, Miklitz Carolin, Müller Anna, Oender Demet, Polcher Alexandra, Purrer Veronika, Röske Sandra, Schneider Christine, Schneider Anja, Spottke Annika, Vogt Ina, Wagner Michael, wolfsgruber Steffen, Yilmaz Sagik, Bartels Claudia, Dechent Peter, Hansen Niels, Hassoun Lina, Hirschel Sina, Nuhn Sabine, Pfahlert Ilona, Rausch Lena, Schott Björn, Timäus Charles, Werner Christine, Wiltfang Jens, Zabel Lioba, Zech Heike, Bader Abdelmajid, Baldermann Juan Carlos, Dölle Britta, Drzezga Alexander, Escher Claus, Ghiasi Nasim Roshan, Hardenacke Katja, Jessen Frank, Lützerath Hannah, Maier Franziska, Marquardt Benjamin, Martikke Anja, Meiberth Dix, Petzler Snjezana, Rostamzadeh Ayda, Sannemann Lena, Schild Ann-Katrin, Sorgalla Susanne, Stockter Simone, Thelen Manuela, Tscheuschler Maike, Uhle Franziska, Zeyen Philip, Bittner Daniel, Cardenas-Blanco Arturo, Dobisch Laura, Düzel Emrah, Grieger-Klose Doreen, Hartmann Deike, Metzger Coraline, Nestor Peter, Ruß Christin, Schulze Franziska, Speck Oliver, Yakupov Renat, Ziegler Gabriel, Brauneis Christine, Bürger Katharina, Catak Cihan, Coloma Andrews Lisa, Dichgans Martin, Dörr Angelika, Ertl-Wagner Birgit, Frimmer Daniela, Huber Brigitte, Janowitz Daniel, Kreuzer Max, Markov Eva, Müller Claudia, Rominger Axel, Schmid (ehemals Spreider) Jennifer, Seegerer Anna, Stephan Julia, Zollver Adelgunde, Burow Lena, de Jonge Sylvia, Falkai Peter, Garcia Angarita Natalie, Görlitz Thomas, Gürsel Selim Üstün, Horvath Ildiko, Kurz Carolin, Meisenzahl-Lechner Eva, Perneczky Robert, Utecht Julia, Dyrba Martin, Janecek-Meyer Heike, Kilimann Ingo, Lappe Chris, Lau Esther, Pfaff Henrike, Raum Heike, Sabik Petr, Schmidt Monika, Schulz Heike, Schwarzenboeck Sarah, Teipel Stefan, Weber Marc-Andre, Buchmann Martina, Heger Tanja, Hinderer Petra, Kuder-Buletta Elke, Laske Christoph, Munk Matthias, Mychajliw Christian, Soekadar Surjo, sulzer Patricia, and Trunk Theresia

Subjects
white matter hyperintensities segmentation, evaluation, FLAIR, deep learning, aging, Alzheimer’s disease, Psychiatry, RC435-571
Abstract

BackgroundWhite matter hyperintensities (WMH), a biomarker of small vessel disease, are often found in Alzheimer’s disease (AD) and their advanced detection and quantification can be beneficial for research and clinical applications. To investigate WMH in large-scale multicenter studies on cognitive impairment and AD, appropriate automated WMH segmentation algorithms are required. This study aimed to compare the performance of segmentation tools and provide information on their application in multicenter research.MethodsWe used a pseudo-randomly selected dataset (n = 50) from the DZNE-multicenter observational Longitudinal Cognitive Impairment and Dementia Study (DELCODE) that included 3D fluid-attenuated inversion recovery (FLAIR) images from participants across the cognitive continuum. Performances of top-rated algorithms for automated WMH segmentation [Brain Intensity Abnormality Classification Algorithm (BIANCA), lesion segmentation toolbox (LST), lesion growth algorithm (LGA), LST lesion prediction algorithm (LPA), pgs, and sysu_media] were compared to manual reference segmentation (RS).ResultsAcross tools, segmentation performance was moderate for global WMH volume and number of detected lesions. After retraining on a DELCODE subset, the deep learning algorithm sysu_media showed the highest performances with an average Dice’s coefficient of 0.702 (±0.109 SD) for volume and a mean F1-score of 0.642 (±0.109 SD) for the number of lesions. The intra-class correlation was excellent for all algorithms (>0.9) but BIANCA (0.835). Performance improved with high WMH burden and varied across brain regions.ConclusionTo conclude, the deep learning algorithm, when retrained, performed well in the multicenter context. Nevertheless, the performance was close to traditional methods. We provide methodological recommendations for future studies using automated WMH segmentation to quantify and assess WMH along the continuum of cognitive impairment and AD dementia.

Published
2023
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10. Single-value fMRI scores reflect both stage and risk across the Alzheimer's disease continuum

Author

Soch, Joram, primary, Richter, Anni, additional, Kizilirmak, Jasmin M., additional, Schütze, Hartmut, additional, Ziegler, Gabriel, additional, Altenstein, Slawek, additional, Brosseron, Frederic, additional, Fliessbach, Klaus, additional, Freiesleben, Silka Dawn, additional, Glanz, Wenzel, additional, Gref, Daria, additional, Heneka, Michael T., additional, Incesoy, Enise I., additional, Kilimann, Ingo, additional, Kimmich, Okka, additional, Laske, Christoph, additional, Lohse, Andrea, additional, Lüsebrink, Falk, additional, Munk, Matthias H., additional, Peters, Oliver, additional, Preis, Lukas, additional, Priller, Josef, additional, Ramirez, Alfredo, additional, Roeske, Sandra, additional, Rostamzadeh, Ayda, additional, Roy-Kluth, Nina, additional, Schneider, Anja, additional, Spottke, Annika, additional, Spruth, Eike Jakob, additional, Teipel, Stefan, additional, Wiltfang, Jens, additional, Jessen, Frank, additional, Wagner, Michael, additional, Düzel, Emrah, additional, and Schott, Björn H., additional

Published
2023
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11. Relevance of Minor Neuropsychological Deficits in Patients With Subjective Cognitive Decline

Author

Stark, Melina, primary, Wolfsgruber, Steffen, additional, Kleineidam, Luca, additional, Frommann, Ingo, additional, Altenstein, Slawek, additional, Bartels, Claudia, additional, Brosseron, Frederic, additional, Buerger, Katharina, additional, Burow, Lena, additional, Butryn, Michaela, additional, Ewers, Michael, additional, Fliessbach, Klaus, additional, Gabelin, Tatjana, additional, Glanz, Wenzel, additional, Goerss, Doreen, additional, Gref, Daria, additional, Hansen, Niels, additional, Heneka, Michael T., additional, Hinderer, Petra, additional, Incesoy, Enise I, additional, Janowitz, Daniel, additional, Kilimann, Ingo, additional, Kimmich, Okka, additional, Laske, Christoph, additional, Munk, Matthias H., additional, Perneczky, Robert, additional, Peters, Oliver, additional, Preis, Lukas, additional, Priller, Josef, additional, Rauchmann, Boris-Stephan, additional, Rostamzadeh, Ayda, additional, Roy-Kluth, Nina, additional, Sanzenbacher, Carolin, additional, Schneider, Anja, additional, Schott, Björn H., additional, Spottke, Annika, additional, Spruth, Eike Jakob, additional, Teipel, Stefan, additional, Vogt, Ina R, additional, Wiltfang, Jens, additional, Duzel, Emrah, additional, Jessen, Frank, additional, and Wagner, Michael, additional

Published
2023
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12. The comorbidity and co-medication profile of patients with progressive supranuclear palsy

Author

Greten, Stephan, primary, Wegner, Florian, additional, Jensen, Ida, additional, Krey, Lea, additional, Rogozinski, Sophia, additional, Fehring, Meret, additional, Heine, Johanne, additional, Doll-Lee, Johanna, additional, Pötter-Nerger, Monika, additional, Zeitzschel, Molly, additional, Hagena, Keno, additional, Pedrosa, David J., additional, Eggers, Carsten, additional, Bürk, Katrin, additional, Trenkwalder, Claudia, additional, Claus, Inga, additional, Warnecke, Tobias, additional, Süß, Patrick, additional, Winkler, Jürgen, additional, Gruber, Doreen, additional, Gandor, Florin, additional, Berg, Daniela, additional, Paschen, Steffen, additional, Classen, Joseph, additional, Pinkhardt, Elmar H., additional, Kassubek, Jan, additional, Jost, Wolfgang H., additional, Tönges, Lars, additional, Kühn, Andrea A., additional, Schwarz, Johannes, additional, Peters, Oliver, additional, Dashti, Eman, additional, Priller, Josef, additional, Spruth, Eike J., additional, Krause, Patricia, additional, Spottke, Annika, additional, Schneider, Anja, additional, Beyle, Aline, additional, Kimmich, Okka, additional, Donix, Markus, additional, Haussmann, Robert, additional, Brandt, Moritz, additional, Dinter, Elisabeth, additional, Wiltfang, Jens, additional, Schott, Björn H., additional, Zerr, Inga, additional, Bähr, Mathias, additional, Buerger, Katharina, additional, Janowitz, Daniel, additional, Perneczky, Robert, additional, Rauchmann, Boris-Stephan, additional, Weidinger, Endy, additional, Levin, Johannes, additional, Katzdobler, Sabrina, additional, Düzel, Emrah, additional, Glanz, Wenzel, additional, Teipel, Stefan, additional, Kilimann, Ingo, additional, Prudlo, Johannes, additional, Gasser, Thomas, additional, Brockmann, Kathrin, additional, Hoffmann, Daniel C., additional, Klockgether, Thomas, additional, Krause, Olaf, additional, Heck, Johannes, additional, Höglinger, Günter U., additional, and Klietz, Martin, additional

Published
2023
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13. Perivascular space enlargement accelerates with hypertension, white matter hyperintensities, chronic inflammation, and Alzheimer's disease pathology: evidence from a three-year longitudinal multicentre study

Author

Menze, Inga, primary, Bernal, Jose, additional, Kaya, Pinar, additional, Aki, Çağla, additional, Pfister, Malte, additional, Geisendörfer, Jonas, additional, Yakupov, Renat, additional, Heneka, Michael T., additional, Brosseron, Frederic, additional, Schmid, Matthias C., additional, Glanz, Wenzel, additional, Incesoy, Enise I., additional, Butryn, Michaela, additional, Rostamzadeh, Ayda, additional, Meiberth, Dix, additional, Peters, Oliver, additional, Preis, Lukas, additional, Lammerding, Dominik, additional, Gref, Daria, additional, Priller, Josef, additional, Spruth, Eike J., additional, Altenstein, Slawek, additional, Lohse, Andrea, additional, Hetzer, Stefan, additional, Schneider, Anja, additional, Fliessbach, Klaus, additional, Kimmich, Okka, additional, Vogt, Ina R., additional, Wiltfang, Jens, additional, Bartels, Claudia, additional, Schott, Björn H., additional, Hansen, Niels, additional, Dechent, Peter, additional, Buerger, Katharina, additional, Janowitz, Daniel, additional, Perneczky, Robert, additional, Rauchmann, Boris-Stephan, additional, Teipel, Stefan, additional, Kilimann, Ingo, additional, Goerss, Doreen, additional, Laske, Christoph, additional, Munk, Matthias H., additional, Sanzenbacher, Carolin, additional, Hinderer, Petra, additional, Scheffler, Klaus, additional, Spottke, Annika, additional, Roy-Kluth, Nina, additional, Lüsebrink, Falk, additional, Neumann, Katja, additional, Jessen, Frank, additional, Schreiber, Stefanie, additional, Düzel, Emrah, additional, and Ziegler, Gabriel, additional

Published
2023
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15. Plasma extracellular vesicle Tau isoform ratios and TDP-43 inform about molecular pathology in Frontotemporal Dementia and Amyotrophic Lateral Sclerosis

Author

Chatterjee, Madhurima, primary, Özdemir, Selcuk, additional, Fritz, Christian, additional, Möbius, Wiebke, additional, Kleineidam, Luca, additional, Mandelkow, Eckhard, additional, Biernat, Jacek, additional, Dogdu, Cem, additional, Peters, Oliver, additional, Cosma, Nicoleta Carmen, additional, Wang, Xiao, additional, Schneider, Luisa-Sophia, additional, Priller, Josef, additional, Spruth, Eicke, additional, Kühn, Andrea, additional, Krause, Patricia, additional, Klockgether, Thomas, additional, Vogt, Ina, additional, Kimmich, Okka, additional, Spottke, Annika, additional, Hoffmann, Daniel, additional, Fliessbach, Klaus, additional, Miklitz, Carolin, additional, McCormick, Cornelia, additional, Falkenburger, Björn, additional, Brandt, Moritz, additional, Günther, Rene, additional, Dinter, Elisabeth, additional, Wiltfang, Jens, additional, Hansen, Niels, additional, Baehr, Mathias, additional, Zerr, Inga, additional, Flöel, Agnes, additional, Nestor, Peter, additional, Düzel, Emrah, additional, Glanz, Wenzel, additional, Incesoy, Enise, additional, Buerger, Katharina, additional, Janowitz, Daniel, additional, Perneczky, Robert, additional, Rauchmann, Boris-Stephan, additional, Hopfner, Franziska, additional, Levin, Johannes, additional, Teipel, Stefan, additional, Kilimann, Ingo, additional, Goerss, Doreen, additional, Prudlo, Johannes, additional, Gasser, Thomas, additional, Brockmann, Kathrin, additional, Synofzik, Matthis, additional, Wilke, Carlo, additional, Wagner, Michael, additional, Frommann, Ingo, additional, Roeske, Sandra, additional, Betram, Lucas, additional, Heneka, Michael, additional, Brosseron, Frederic, additional, Ramirez, Alfredo, additional, Schmid, Matthias, additional, Beschorner, Rudi, additional, Halle, Annett, additional, Herms, Jochen, additional, Neuman, Manuela, additional, Barthelemy, Nicolas, additional, Bateman, Randall, additional, Rizzu, Patrizia, additional, Heutink, Peter, additional, Höglinger, Günter, additional, Hermann, Andreas, additional, and Schneider, Anja, additional

Published
2023
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16. Novelty-Related fMRI Responses of Precuneus and Medial Temporal Regions in Individuals at Risk for Alzheimer Disease

Author

Billette, Ornella V, Ziegler, Gabriel, Dahmen, Philip, Dechent, Peter, Dobisch, Laura, Fliessbach, Klaus, Freiesleben, Silka Dawn, Glanz, Wenzel, Göerß, Doreen, Haynes, John Dylan, Heneka, Michael T, Kilimann, Ingo, Aruci, Merita, Kimmich, Okka, Kleineidam, Luca, Laske, Christoph, Lohse, Andrea, Rostamzadeh, Ayda, Metzger, Coraline, Munk, Matthias H, Peters, Oliver, Preis, Lukas, Priller, Josef, Schütze, Hartmut, Scheffler, Klaus, Schneider, Anja, Spottke, Annika, Spruth, Eike Jakob, Ramirez, Alfredo, Röske, Sandra, Roy, Nina, Teipel, Stefan, Wagner, Michael, Wiltfang, Jens, Kizilirmak, Jasmin M, Wolfsgruber, Steffen, Yakupov, Renat, Zeidman, Peter, Jessen, Frank, Schott, Björn, Düzel, Emrah, Maass, Anne, Group, DELCODE Study, Richter, Anni, Altenstein, Slawek, Bartels, Claudia, Brosseron, Frederic, and Cardenas-Blanco, Arturo

Subjects
Alzheimer Disease/diagnosis, Amyloid beta-Peptides, Cognitive Dysfunction/diagnostic imaging, diagnosis [Alzheimer Disease], diagnostic imaging [Cognitive Dysfunction], Magnetic Resonance Imaging, Temporal Lobe/diagnostic imaging, Temporal Lobe, Magnetic Resonance Imaging/methods, diagnostic imaging [Parietal Lobe], Parietal Lobe/diagnostic imaging, methods [Magnetic Resonance Imaging], diagnostic imaging [Temporal Lobe], Alzheimer Disease, Parietal Lobe, Humans, Cognitive Dysfunction, ddc:610, Neurology (clinical), Biomarkers
Abstract

Background and ObjectivesWe assessed whether novelty-related fMRI activity in medial temporal lobe regions and the precuneus follows an inverted U-shaped pattern across the clinical spectrum of increased Alzheimer disease (AD) risk as previously suggested. Specifically, we tested for potentially increased activity in individuals with a higher AD risk due to subjective cognitive decline (SCD) or mild cognitive impairment (MCI). We further tested whether activity differences related to diagnostic groups were accounted for by CSF markers of AD or brain atrophy.MethodsWe studied 499 participants aged 60–88 years from the German Center for Neurodegenerative Diseases Longitudinal Cognitive Impairment and Dementia Study (DELCODE) who underwent task-fMRI. Participants included 163 cognitively normal (healthy control, HC) individuals, 222 SCD, 82 MCI, and 32 patients with clinical diagnosis of mild AD. CSF levels of β-amyloid 42/40 ratio and phosphorylated-tau181 were available from 232 participants. We used region-based analyses to assess novelty-related activity (novel > highly familiar scenes) in entorhinal cortex, hippocampus, and precuneus as well as whole-brain voxel-wise analyses. First, general linear models tested differences in fMRI activity between participant groups. Complementary regression models tested quadratic relationships between memory impairment and activity. Second, relationships of activity with AD CSF biomarkers and brain volume were analyzed. Analyses were controlled for age, sex, study site, and education.ResultsIn the precuneus, we observed an inverted U-shaped pattern of novelty-related activity across groups, with higher activity in SCD and MCI compared with HC, but not in patients with AD who showed relatively lower activity than MCI. This nonlinear pattern was confirmed by a quadratic relationship between memory impairment and precuneus activity. Precuneus activity was not related to AD biomarkers or brain volume. In contrast to the precuneus, hippocampal activity was reduced in AD dementia compared with all other groups and related to AD biomarkers.DiscussionNovelty-related activity in the precuneus follows a nonlinear pattern across the clinical spectrum of increased AD risk. Although the underlying mechanism remains unclear, increased precuneus activity might represent an early signature of memory impairment. Our results highlight the nonlinearity of activity alterations that should be considered in clinical trials using functional outcome measures or targeting hyperactivity.

Published
2022

17. Next-generation phenotyping integrated in a national framework for patients with ultra-rare disorders improves genetic diagnostics and yields new molecular findings

Author

Schmidt, Axel, primary, Danyel, Magdalena, additional, Grundmann, Kathrin, additional, Brunet, Theresa, additional, Klinkhammer, Hannah, additional, Hsieh, Tzung-Chien, additional, Engels, Hartmut, additional, Peters, Sophia, additional, Knaus, Alexej, additional, Moosa, Shahida, additional, Averdunk, Luisa, additional, Boschann, Felix, additional, Sczakiel, Henrike, additional, Schwartzmann, Sarina, additional, Mensah, Martin Atta, additional, Pantel, Jean Tori, additional, Holtgrewe, Manuel, additional, Boesch, Annemarie, additional, Weiss, Claudia, additional, Weinhold, Natalie, additional, Suter, Aude-Annick, additional, Stoltenburg, Corinna, additional, Neugebauer, Julia, additional, Kallinich, Tillmann, additional, Kaindl, Angela M., additional, Holzhauer, Susanne, additional, Buehrer, Christoph, additional, Bufler, Philip, additional, Kornak, Uwe, additional, Ott, Claus-Eric, additional, Schuelke, Markus, additional, Nguyen, Hoa Huu Phuc, additional, Hoffjan, Sabine, additional, Grasemann, Corinna, additional, Rothoeft, Tobias, additional, Brinkmann, Folke, additional, Matar, Nora, additional, Sivalingam, Sugirthan, additional, Perne, Claudia, additional, Mangold, Elisabeth, additional, Kreiss, Martina, additional, Cremer, Kirsten, additional, Betz, Regina C., additional, Bender, Tim, additional, Muecke, Martin, additional, Grigull, Lorenz, additional, Klockgether, Thomas, additional, Isabel, Spier, additional, Heimbach, Andre, additional, Tim, Bender, additional, Brand, Fabian, additional, Stieber, Christiane, additional, Morawiec, Alexandra Marzena, additional, Karakostas, Pantelis, additional, Schaefer, Valentin S., additional, Bernsen, Sarah, additional, Weydt, Patrick, additional, Castro-Gomez, Sergio, additional, Aziz, Ahmad, additional, Grobe-Einsler, Marcus, additional, Kimmich, Okka, additional, Kobeleva, Xenia, additional, oender, Demet, additional, Lesmann, Hellen, additional, Kumar, Sheetal, additional, Tacik, Pawel, additional, Lee-Kirsch, Min Ae, additional, Berner, Reinhard, additional, Schuetz, Catharina, additional, Koerholz, Julia, additional, Kretschmer, Tanita, additional, Di Donato, Nataliya, additional, Schroeck, Evelin, additional, Heinen, Andre, additional, Reuner, Ulrike, additional, Hansske, Amalia-Mihaela, additional, Kaiser, Frank J., additional, Manka, Eva, additional, Munteanu, Martin, additional, Kuechler, Alma, additional, Cordula, Kiewert, additional, Hirtz, Raphael, additional, Schlapakow, Elena, additional, Schlein, Christian, additional, Lisfeld, Jasmin, additional, Kubisch, Christian, additional, Herget, Theresia, additional, Hempel, Maja, additional, Weiler-Normann, Christina, additional, Ullrich, Kurt, additional, Schramm, Christoph, additional, Rudolph, Cornelia, additional, Rillig, Franziska, additional, Groffmann, Maximilian, additional, Muntau, Ania, additional, Tibelius, Alexandra, additional, Schwaibold, Eva M. C., additional, Schaaf, Christian P., additional, Zawada, Michal, additional, Kaufmann, Lilian, additional, Hinderhofer, Katrin, additional, Okun, Pamela M., additional, Kotzaeridou, Urania, additional, Hoffmann, Georg F., additional, Choukair, Daniela, additional, Bettendorf, Markus, additional, Spielmann, Malte, additional, Ripke, Annekatrin, additional, Pauly, Martje, additional, Muenchau, Alexander, additional, Lohmann, Katja, additional, Huening, Irina, additional, Hanker, Britta, additional, Baeumer, Tobias, additional, Herzog, Rebecca, additional, Hellenbroich, Yorck, additional, Westphal, Dominik S., additional, Strom, Tim, additional, Kovacs, Reka, additional, Riedhammer, Korbinian M., additional, Mayerhanser, Katharina, additional, Graf, Elisabeth, additional, Brugger, Melanie, additional, Hoefele, Julia, additional, Oexle, Konrad, additional, Mirza-Schreiber, Nazanin, additional, Berutti, Riccardo, additional, Schatz, Ulrich, additional, Krenn, Martin, additional, Makowski, Christine, additional, Weigand, Heike, additional, Schroeder, Sebastian, additional, Rohlfs, Meino, additional, Katharina, Vill, additional, Hauck, Fabian, additional, Borggraefe, Ingo, additional, Mueller-Felber, Wolfgang, additional, Kurth, Ingo, additional, Elbracht, Miriam, additional, Knopp, Cordula, additional, Begemann, Matthias, additional, Kraft, Florian, additional, Lemke, Johannes, additional, Hentschel, Julia, additional, Platzer, Konrad, additional, Strehlow, Vincent, additional, Abou Jamra, Rami, additional, Kehrer, Martin, additional, Demidov, German, additional, Beck-Woedl, Stefanie, additional, Graessner, Holm, additional, Sturm, Marc, additional, Zeltner, Lena, additional, Schoels, Ludger J., additional, Magg, Janine, additional, Bevot, Andrea, additional, Kehrer, Christiane, additional, Kaiser, Nadja, additional, Horn, Denise, additional, Grueters-Kieslich, Annette, additional, Klein, Christoph, additional, Mundlos, Stefan, additional, Noethen, Markus, additional, Riess, Olaf, additional, Meitinger, Thomas, additional, Krude, Heiko, additional, Krawitz, Peter M., additional, Haack, Tobias, additional, Ehmke, Nadja, additional, and Wagner, Matias, additional

Published
2023
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18. A 6-items Questionnaire (6-QMD) captures a Mediterranean like dietary pattern and is associated with memory performance and hippocampal volume in elderly and persons at risk for Alzheimer’s disease

Author

Rauchmann, Boris-Stephan, primary, Gross, Patrizia, additional, Ersoezlue, Ersin, additional, Wagner, Michael, additional, Tommaso, Ballarini, additional, Kurz, Carolin, additional, Tatò, Maia, additional, Utecht, Julia, additional, Papazov, Boris, additional, Guersel, Selim, additional, Totzke, Marie, additional, Trappmann, Lena, additional, Burow, Lena, additional, Koller, Gabriele, additional, Stöcklein, Sophia, additional, Keeser, Daniel, additional, Altenstein, Slawek, additional, Bartels, Claudia, additional, Buerger, Katharina, additional, Dechent, Peter, additional, Dobisch, Laura, additional, Ewers, Michael, additional, Fliessbach, Klaus, additional, Freiesleben, Silka Dawn, additional, Glanz, Wenzel, additional, Goeerss, Doreen, additional, Gref, Daria, additional, Haynes, John Dylan, additional, Janowitz, Daniel, additional, Kilimann, Ingo, additional, Kimmich, Okka, additional, Kleineidam, Luca, additional, Laske, Christoph, additional, Lohse, Andrea, additional, Maier, Franziska, additional, Metzger, Coraline D., additional, Munk, Matthias H., additional, Peters, Oliver, additional, Preis, Lukas, additional, Priller, Josef, additional, Roeske, Sandra, additional, Roy, Nina, additional, Sanzenbacher, Carolin, additional, Scheffler, Klaus, additional, Schneider, Anja, additional, Schott, Björn Hendrik, additional, Spottke, Annika, additional, Spruth, Eike Jakob, additional, Teipel, Stefan, additional, van Lent, Debora Melo, additional, Wiltfang, Jens, additional, Wolfsgruber, Steffen, additional, Yakupov, Renat, additional, Düzel, Emrah, additional, Jessen, Frank, additional, and Perneczky, Robert, additional

Published
2023
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19. A Cognitive Reserve Network That Moderates the Relationship Between Alzheimer’s Disease Pathology and Cognition

Author

Vockert, Niklas, primary, Schütze, Hartmut, additional, Richter, Anni, additional, Altenstein, Slawek, additional, Bartels, Claudia, additional, Brosseron, Frederic, additional, Cardenas‐Blanco, Arturo, additional, Dahmen, Philip, additional, Dechent, Peter, additional, Dobisch, Laura, additional, Fließbach, Klaus, additional, Freiesleben, Silka Dawn, additional, Glanz, Wenzel, additional, Goerss, Doreen, additional, Haynes, John‐Dylan, additional, Heneka, Michael T., additional, Kilimann, Ingo, additional, Kimmich, Okka, additional, Kleineidam, Luca, additional, Laske, Christoph, additional, Lohse, Andrea, additional, Metzger, Coraline D., additional, Munk, Matthias H. J., additional, Peters, Oliver, additional, Preis, Lukas, additional, Priller, Josef, additional, Ramirez, Alfredo, additional, Roeske, Sandra, additional, Rostamzadeh, Ayda, additional, Roy, Nina, additional, Scheffler, Klaus, additional, Schneider, Anja, additional, Spottke, Annika, additional, Spruth, Eike Jakob, additional, Teipel, Stefan, additional, Wagner, Michael, additional, Wiltfang, Jens, additional, Wolfsgruber, Steffen, additional, Yakupov, Renat, additional, Zeidman, Peter, additional, Jessen, Frank, additional, Schott, Björn H, additional, Duzel, Emrah, additional, Maass, Anne, additional, and Ziegler, Gabriel, additional

Published
2022
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20. Potential of Non-Coding RNA as Biomarkers for Progressive Supranuclear Palsy

Author

Simoes, Fabio A., primary, Joilin, Greig, additional, Peters, Oliver, additional, Schneider, Luisa-Sophie, additional, Priller, Josef, additional, Spruth, Eike Jakob, additional, Vogt, Ina, additional, Kimmich, Okka, additional, Spottke, Annika, additional, Hoffmann, Daniel C., additional, Falkenburger, Björn, additional, Brandt, Moritz, additional, Prudlo, Johannes, additional, Brockmann, Kathrin, additional, Fries, Franca Laura, additional, Rowe, James B., additional, Church, Alistair, additional, Respondek, Gesine, additional, Newbury, Sarah F., additional, Leigh, P. Nigel, additional, Morris, Huw R., additional, Höglinger, Günter U., additional, and Hafezparast, Majid, additional

Published
2022
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21. Novelty-Related fMRI Responses of Precuneus and Medial Temporal Regions in Individuals at Risk for Alzheimer Disease

Author

Billette, Ornella, V, Ziegler, Gabriel, Aruci, Merita, Schuetze, Hartmut, Kizilirmak, Jasmin M., Richter, Anni, Altenstein, Slawek, Bartels, Claudia, Brosseron, Frederic, Cardenas-Blanco, Arturo, Dahmen, Philip, Dechent, Peter, Dobisch, Laura, Fliessbach, Klaus, Freiesleben, Silka Dawn, Glanz, Wenzel, Goeerss, Doreen, Haynes, John Dylan, Heneka, Michael T., Kilimann, Ingo, Kimmich, Okka, Kleineidam, Luca, Laske, Christoph, Lohse, Andrea, Rostamzadeh, Ayda, Metzger, Coraline, Munk, Matthias H., Peters, Oliver, Preis, Lukas, Priller, Josef, Scheffler, Klaus, Schneider, Anja, Spottke, Annika, Spruth, Eike Jakob, Ramirez, Alfredo, Roeske, Sandra, Roy, Nina, Teipel, Stefan, Wagner, Michael, Wiltfang, Jens, Wolfsgruber, Steffen, Yakupov, Renat, Zeidman, Peter, Jessen, Frank, Schott, Bjorn H., Duezel, Emrah, Maass, Anne, Billette, Ornella, V, Ziegler, Gabriel, Aruci, Merita, Schuetze, Hartmut, Kizilirmak, Jasmin M., Richter, Anni, Altenstein, Slawek, Bartels, Claudia, Brosseron, Frederic, Cardenas-Blanco, Arturo, Dahmen, Philip, Dechent, Peter, Dobisch, Laura, Fliessbach, Klaus, Freiesleben, Silka Dawn, Glanz, Wenzel, Goeerss, Doreen, Haynes, John Dylan, Heneka, Michael T., Kilimann, Ingo, Kimmich, Okka, Kleineidam, Luca, Laske, Christoph, Lohse, Andrea, Rostamzadeh, Ayda, Metzger, Coraline, Munk, Matthias H., Peters, Oliver, Preis, Lukas, Priller, Josef, Scheffler, Klaus, Schneider, Anja, Spottke, Annika, Spruth, Eike Jakob, Ramirez, Alfredo, Roeske, Sandra, Roy, Nina, Teipel, Stefan, Wagner, Michael, Wiltfang, Jens, Wolfsgruber, Steffen, Yakupov, Renat, Zeidman, Peter, Jessen, Frank, Schott, Bjorn H., Duezel, Emrah, and Maass, Anne

Abstract

Background and Objectives We assessed whether novelty-related fMRI activity in medial temporal lobe regions and the precuneus follows an inverted U-shaped pattern across the clinical spectrum of increased Alzheimer disease (AD) risk as previously suggested. Specifically, we tested for potentially increased activity in individuals with a higher AD risk due to subjective cognitive decline (SCD) or mild cognitive impairment (MCI). We further tested whether activity differences related to diagnostic groups were accounted for by CSF markers of AD or brain atrophy. Methods We studied 499 participants aged 60-88 years from the German Center for Neurodegenerative Diseases Longitudinal Cognitive Impairment and Dementia Study (DELCODE) who underwent task-fMRI. Participants included 163 cognitively normal (healthy control, HC) individuals, 222 SCD, 82 MCI, and 32 patients with clinical diagnosis of mild AD. CSF levels of beta-amyloid 42/40 ratio and phosphorylated-tau181 were available from 232 participants. We used region-based analyses to assess novelty-related activity (novel > highly familiar scenes) in entorhinal cortex, hippocampus, and precuneus as well as whole-brain voxel-wise analyses. First, general linear models tested differences in fMRI activity between participant groups. Complementary regression models tested quadratic relationships between memory impairment and activity. Second, relationships of activity with AD CSF biomarkers and brain volume were analyzed. Analyses were controlled for age, sex, study site, and education. Results In the precuneus, we observed an inverted U-shaped pattern of novelty-related activity across groups, with higher activity in SCD and MCI compared with HC, but not in patients with AD who showed relatively lower activity than MCI. This nonlinear pattern was confirmed by a quadratic relationship between memory impairment and precuneus activity. Precuneus activity was not related to AD biomarkers or brain volume. In contrast to the pre

Published
2022

22. Individualized Gaussian Process-based Prediction of Memory Performance and Biomarker Status in Ageing and Alzheimer's disease

Author

Nemali, Aditya, primary, Vockert, Niklas, additional, Berron, David, additional, Maas, Anne, additional, Yakupov, Renat, additional, Peters, Oliver, additional, Gref, Daria, additional, Cosma, Nicoleta, additional, Preis, Lukas, additional, Priller, Josef, additional, Spruth, Eike Jakob, additional, Altenstein, Slawek, additional, Lohse, Andrea, additional, Fliessbach, Klaus, additional, Kimmich, Okka, additional, Vogt, Ina, additional, Wiltfang, Jens, additional, Hansen, Niels, additional, Bartels, Claudia, additional, H. Schott, Björn, additional, Maier, Franziska, additional, Meiberth, Dix, additional, Glanz, Wenzel, additional, Incesoy, Enise, additional, Butryn, Michaela, additional, Buerger, Katharina, additional, Janowitz, Daniel, additional, Ewers, Michael, additional, Perneczky, Robert, additional, Rauchmann, Boris-Stephan, additional, Burow, Lena, additional, Teipel, Stefan, additional, Kilimann, Ingo, additional, Göerß, Doreen, additional, Dyrba, Martin, additional, Laske, Christoph, additional, Munk, Matthias H., additional, Sanzenbacher, Carolin, additional, Müller, Stephan, additional, Spottke, Annika, additional, Roy, Nina, additional, Heneka, Michael T., additional, Brosseron, Frederic, additional, Röske, Sandra, additional, Dobisch, Laura, additional, Ramirez, Alfredo, additional, Dechent, Peter, additional, Scheffler, Klaus, additional, Kleineidam, Luca, additional, Wolfsgruber, Steffen, additional, Wagner, Michael, additional, Jessen, Frank, additional, Düzel, Emrah, additional, and Ziegler, Gabriel, additional

Published
2022
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30. Unusual polytopic pleomorphic tumor of the CNS: a case report

Author

Igressa, Alhadi, Herrlinger, Ulrich, Deckert, Martina, Spreer, Joachim, Kimmich, Okka, Hartmann, Alexander, Liebetrau, Ulrich, Borger, Volker, and Nakamura, Makoto

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Objective: We present a patient with a polytopic CNS tumour raising the differential diagnosis of an unusual histiocytic tumour and an anaplastic glioma. Several biopsies of brain and spinal lesions with repeated histological and immunohistochemical analyses showed cell characteristics indicating mainly[for full text, please go to the a.m. URL], 68. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), 7. Joint Meeting mit der Society of British Neurological Surgeons (SBNS)

Published
2017

31. ¹⁸F-fluoroethyl-L-tyrosine positron emission tomography-guided diagnosis of a malignant intramedullary spinal cord tumor

Author

Kebir, Sied, Kimmich, Okka, Niehusmann, Pitt, Gaertner, Florian C., Essler, Markus, Landsberg, Jennifer, Klockgether, Thomas, Simon, Matthias, Herrlinger, Ulrich, and Glas, Martin

Subjects
Medizin
Abstract

Diagnosis in patients with a suspected malignant intramedullary lesion that requires biopsy for definitive diagnosis may be challenging, as spinal cord surgery carries the risk of irreversible neurological deficits. The current study presents the first case of¹⁸F-fluoroethyl-L-tyrosine (¹⁸F-FET) positron emission tomography (PET) imaging in a patient with a spinal cord tumor. The patient was unsuitable for magnetic resonance imaging due to his implanted cardiac defibrillator.¹⁸F-FET PET indicated a high-grade malignancy of the spinal cord, justifying tumor biopsy. Histological analysis was compatible with a malignant melanoma. This is also the first report demonstrating the FET-PET appearance/metabolic phenotype of a malignant melanoma of the spinal cord.

Published
2016

32. A Headset Method for Measuring the Visual Temporal Discrimination Threshold in Cervical Dystonia

Author

Molloy, Anna, Williams, Laura, Kimmich, Okka, Butler, John S., Quinlivan, Brendan, Dabacan, Adriana, Fanning, Aisling, O'Riordan, Sean, Reilly, Richard B., and Hutchinson, Michael

Subjects
headset, 0303 health sciences, lcsh:Diseases of the musculoskeletal system, 0206 medical engineering, Cervical dystonia, 02 engineering and technology, Temporal discrimination threshold, Headset, 020601 biomedical engineering, lcsh:RC346-429, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, temporal discrimination threshold, Brief Reports, lcsh:RC925-935, 10. No inequality, 030217 neurology & neurosurgery, lcsh:Neurology. Diseases of the nervous system, 030304 developmental biology
Abstract

Background: The visual temporal discrimination threshold (TDT) is the shortest time interval at which one can determine two stimuli to be asynchronous and meets criteria for a valid endophenotype in adult‐onset idiopathic focal dystonia, a poorly penetrant disorder. Temporal discrimination is assessed in the hospital laboratory; in unaffected relatives of multiplex adult‐onset dystonia patients distance from the hospital is a barrier to data acquisition. We devised a portable headset method for visual temporal discrimination determination and our aim was to validate this portable tool against the traditional laboratory‐based method in a group of patients and in a large cohort of healthy controls. Methods: Visual TDTs were examined in two groups 1) in 96 healthy control participants divided by age and gender, and 2) in 33 cervical dystonia patients, using two methods of data acquisition, the traditional table‐top laboratory‐based system, and the novel portable headset method. The order of assessment was randomized in the control group. The results obtained by each technique were compared. Results: Visual temporal discrimination in healthy control participants demonstrated similar age and gender effects by the headset method as found by the table‐top examination. There were no significant differences between visual TDTs obtained using the two methods, both for the control participants and for the cervical dystonia patients. Bland–Altman testing showed good concordance between the two methods in both patients and in controls. Discussion: The portable headset device is a reliable and accurate method for visual temporal discrimination testing for use outside the laboratory, and will facilitate increased TDT data collection outside of the hospital setting. This is of particular importance in multiplex families where data collection in all available members of the pedigree is important for exome sequencing studies., Tremor and Other Hyperkinetic Movements, Tremor and Other Hyperkinetic Movements

Published
2014

37. Cervical Dystonia: A Disorder of the Midbrain Network for Covert Attentional Orienting

Author

Hutchinson, Michael, primary, Isa, Tadashi, additional, Molloy, Anna, additional, Kimmich, Okka, additional, Williams, Laura, additional, Molloy, Fiona, additional, Moore, Helena, additional, Healy, Daniel G., additional, Lynch, Tim, additional, Walsh, Cathal, additional, Butler, John, additional, Reilly, Richard B., additional, Walsh, Richard, additional, and O’Riordan, Sean, additional

Published
2014
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41. 18F-fluoroethyl-L-tyrosine positron emission tomography-guided diagnosis of a malignant intramedullary spinal cord tumor.

Author

KEBIR, SIED, KIMMICH, OKKA, NIEHUSMANN, PITT, GAERTNER, FLORIAN C., ESSLER, MARKUS, LANDSBERG, JENNIFER, KLOCKGETHER, THOMAS, SIMON, MATTHIAS, HERRLINGER, ULRICH, and GLAS, MARTIN

Subjects
*TYROSINE, *SPINAL cord tumors, *POSITRON emission tomography, *SPINAL cord surgery, *DEFIBRILLATORS, *DIAGNOSIS
Abstract

Diagnosis in patients with a suspected malignant intramedullary lesion that requires biopsy for definitive diagnosis may be challenging, as spinal cord surgery carries the risk of irreversible neurological deficits. The current study presents the first case of 18F-fluoroethyl-L-tyrosine (18F-FET) positron emission tomography (PET) imaging in a patient with a spinal cord tumor. The patient was unsuitable for magnetic resonance imaging due to his implanted cardiac defibrillator. 18F-FET PET indicated a high-grade malignancy of the spinal cord, justifying tumor biopsy. Histological analysis was compatible with a malignant melanoma. This is also the first report demonstrating the FET-PET appearance/metabolic phenotype of a malignant melanoma of the spinal cord. [ABSTRACT FROM AUTHOR]

Published
2016
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42. A Headset Method for Measuring the Visual Temporal Discrimination Threshold in Cervical Dystonia

Author

Molloy, Anna, Kimmich, Okka, Williams, Laura, Quinlivan, Brendan, Dabacan, Adriana, Fanning, Aisling, Butler, John S., O'Riordan, Sean, Reilly, Richard B., and Hutchinson, Michael

Subjects
FOS: Clinical medicine, Neurosciences, 10. No inequality, 3. Good health
Abstract

Background: The visual temporal discrimination threshold (TDT) is the shortest time interval at which one can determine two stimuli to be asynchronous and meets criteria for a valid endophenotype in adult‐onset idiopathic focal dystonia, a poorly penetrant disorder. Temporal discrimination is assessed in the hospital laboratory; in unaffected relatives of multiplex adult‐onset dystonia patients distance from the hospital is a barrier to data acquisition. We devised a portable headset method for visual temporal discrimination determination and our aim was to validate this portable tool against the traditional laboratory‐based method in a group of patients and in a large cohort of healthy controls. Methods: Visual TDTs were examined in two groups 1) in 96 healthy control participants divided by age and gender, and 2) in 33 cervical dystonia patients, using two methods of data acquisition, the traditional table‐top laboratory‐based system, and the novel portable headset method. The order of assessment was randomized in the control group. The results obtained by each technique were compared. Results: Visual temporal discrimination in healthy control participants demonstrated similar age and gender effects by the headset method as found by the table‐top examination. There were no significant differences between visual TDTs obtained using the two methods, both for the control participants and for the cervical dystonia patients. Bland–Altman testing showed good concordance between the two methods in both patients and in controls. Discussion: The portable headset device is a reliable and accurate method for visual temporal discrimination testing for use outside the laboratory, and will facilitate increased TDT data collection outside of the hospital setting. This is of particular importance in multiplex families where data collection in all available members of the pedigree is important for exome sequencing studies.

43. Single-value brain activity scores reflect both severity and risk across the Alzheimer's continuum.

Author

Soch J, Richter A, Kizilirmak JM, Schütze H, Ziegler G, Altenstein S, Brosseron F, Dechent P, Fliessbach K, Freiesleben SD, Glanz W, Gref D, Heneka MT, Hetzer S, Incesoy EI, Kilimann I, Kimmich O, Kleineidam L, Kuhn E, Laske C, Lohse A, Lüsebrink F, Munk MH, Peters O, Preis L, Priller J, Ramirez A, Roeske S, Rostamzadeh A, Roy-Kluth N, Scheffler K, Schmid M, Schneider A, Spottke A, Spruth EJ, Teipel S, Wiltfang J, Jessen F, Wagner M, Düzel E, and Schott BH

Subjects
Humans, Male, Female, Aged, Middle Aged, Neuropsychological Tests, Severity of Illness Index, Adult, Aged, 80 and over, Apolipoproteins E genetics, Alzheimer Disease genetics, Alzheimer Disease psychology, Alzheimer Disease physiopathology, Magnetic Resonance Imaging, Cognitive Dysfunction physiopathology, Brain diagnostic imaging
Abstract

Single-value scores reflecting the deviation from (FADE score) or similarity with (SAME score) prototypical novelty-related and memory-related functional MRI activation patterns in young adults have been proposed as imaging biomarkers of healthy neurocognitive ageing. Here, we tested the utility of these scores as potential diagnostic and prognostic markers in Alzheimer's disease (AD) and risk states like mild cognitive impairment (MCI) or subjective cognitive decline (SCD). To this end, we analysed subsequent memory functional MRI data from individuals with SCD, MCI and AD dementia as well as healthy controls and first-degree relatives of AD dementia patients (AD-rel) who participated in the multi-centre DELCODE study (n = 468). Based on the individual participants' whole-brain functional MRI novelty and subsequent memory responses, we calculated the FADE and SAME scores and assessed their association with AD risk stage, neuropsychological test scores, CSF amyloid positivity and APOE genotype. Memory-based FADE and SAME scores showed a considerably larger deviation from a reference sample of young adults in the MCI and AD dementia groups compared to healthy controls, SCD and AD-rel. In addition, novelty-based scores significantly differed between the MCI and AD dementia groups. Across the entire sample, single-value scores correlated with neuropsychological test performance. The novelty-based SAME score further differed between Aβ-positive and Aβ-negative individuals in SCD and AD-rel, and between ApoE ɛ4 carriers and non-carriers in AD-rel. Hence, FADE and SAME scores are associated with both cognitive performance and individual risk factors for AD. Their potential utility as diagnostic and prognostic biomarkers warrants further exploration, particularly in individuals with SCD and healthy relatives of AD dementia patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Published
2024
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44. Automated remote speech-based testing of individuals with cognitive decline: Bayesian agreement of transcription accuracy.

Author

König A, Köhler S, Tröger J, Düzel E, Glanz W, Butryn M, Mallick E, Priller J, Altenstein S, Spottke A, Kimmich O, Falkenburger B, Osterrath A, Wiltfang J, Bartels C, Kilimann I, Laske C, Munk MH, Roeske S, Frommann I, Hoffmann DC, Jessen F, Wagner M, Linz N, and Teipel S

Abstract

Introduction: We investigated the agreement between automated and gold-standard manual transcriptions of telephone chatbot-based semantic verbal fluency testing., Methods: We examined 78 cases from the Screening over Speech in Unselected Populations for Clinical Trials in AD (PROSPECT-AD) study, including cognitively normal individuals and individuals with subjective cognitive decline, mild cognitive impairment, and dementia. We used Bayesian Bland-Altman analysis of word count and the qualitative features of semantic cluster size, cluster switches, and word frequencies., Results: We found high levels of agreement for word count, with a 93% probability of a newly observed difference being below the minimally important difference. The qualitative features had fair levels of agreement. Word count reached high levels of discrimination between cognitively impaired and unimpaired individuals, regardless of transcription mode., Discussion: Our results support the use of automated speech recognition particularly for the assessment of quantitative speech features, even when using data from telephone calls with cognitively impaired individuals in their homes., Highlights: High levels of agreement were found between automated and gold-standard manual transcriptions of telephone chatbot-based semantic verbal fluency testing, particularly for word count.The qualitative features had fair levels of agreement.Word count reached high levels of discrimination between cognitively impaired and unimpaired individuals, regardless of transcription mode.Automated speech recognition for the assessment of quantitative and qualitative speech features, even when using data from telephone calls with cognitively impaired individuals in their homes, seems feasible and reliable., Competing Interests: A.K., J.T., E.M., and N.L. are employed by ki:elements. N.L. and J.T. hold shares in the company ki:elements. S.K. has received unrestricted funding from the Alzheimer Drug Discovery Foundation and lecture fees from Eisai. B.F. has received funding from the Deutsche Forschungsgemeinschaft. J.W. has received funding from the BMBF; consulting fees from Immungenetics, Noselab, and Roboscreen; and lecture fees from Beijing Yibai Science and Technology Ltd., Gloryren, Janssen Cilag, Pfizer, Med Update GmbH, Roche Pharma, and Lilly. J.W. participated on a data safety monitoring board or advisory board of Biogen, Abbott, Boehringer Ingelheim, Lilly, MSD Sharp & Dohme, and Roche. C.B. received funding from the German Alzheimer Association and lecture fees from Lilly, Roche Pharma, and Eisai. S.T. participated on scientific advisory boards of Roche Pharma AG, Biogen, Lilly, and Eisai, and received lecture fees from Lilly and Eisai. A.O., E.D., W.G., M.B., J.P., S.A., A.S., O.K., I.K., C.L., M.M., S.R., I.F., D.H., F.J., and M.W. have nothing to disclose. Author disclosures are available in the supporting information., (© 2024 The Author(s). Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Published
2024
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45. Fully Automated MRI-based Analysis of the Locus Coeruleus in Aging and Alzheimer's Disease Dementia using ELSI-Net.

Author

Dünnwald M, Krohn F, Sciarra A, Sarkar M, Schneider A, Fliessbach K, Kimmich O, Jessen F, Rostamzadeh A, Glanz W, Incesoy EI, Teipel S, Kilimann I, Goerss D, Spottke A, Brustkern J, Heneka MT, Brosseron F, Lüsebrink F, Hämmerer D, Düzel E, Tönnies K, Oeltze-Jafra S, and Betts MJ

Abstract

Introduction: The Locus Coeruleus (LC) is linked to the development and pathophysiology of neurodegenerative diseases such as Alzheimer's Disease (AD). Magnetic Resonance Imaging based LC features have shown potential to assess LC integrity in vivo., Methods: We present a Deep Learning based LC segmentation and feature extraction method: ELSI-Net and apply it to healthy aging and AD dementia datasets. Agreement to expert raters and previously published LC atlases were assessed. We aimed to reproduce previously reported differences in LC integrity in aging and AD dementia and correlate extracted features to cerebrospinal fluid (CSF) biomarkers of AD pathology., Results: ELSI-Net demonstrated high agreement to expert raters and published atlases. Previously reported group differences in LC integrity were detected and correlations to CSF biomarkers were found., Discussion: Although we found excellent performance, further evaluations on more diverse datasets from clinical cohorts are required for a conclusive assessment of ELSI-Nets general applicability., Competing Interests: Conflict of interest The authors declare no potential conflict of interests.

Published
2024
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46. 18 F-fluoroethyl-L-tyrosine positron emission tomography-guided diagnosis of a malignant intramedullary spinal cord tumor.

Author

Kebir S, Kimmich O, Niehusmann P, Gaertner FC, Essler M, Landsberg J, Klockgether T, Simon M, Herrlinger U, and Glas M

Abstract

Diagnosis in patients with a suspected malignant intramedullary lesion that requires biopsy for definitive diagnosis may be challenging, as spinal cord surgery carries the risk of irreversible neurological deficits. The current study presents the first case of 18 F-fluoroethyl-L-tyrosine ( 18 F-FET) positron emission tomography (PET) imaging in a patient with a spinal cord tumor. The patient was unsuitable for magnetic resonance imaging due to his implanted cardiac defibrillator. 18 F-FET PET indicated a high-grade malignancy of the spinal cord, justifying tumor biopsy. Histological analysis was compatible with a malignant melanoma. This is also the first report demonstrating the FET-PET appearance/metabolic phenotype of a malignant melanoma of the spinal cord.

Published
2016
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