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1. Different inflammatory signatures based on CSF biomarkers relate to preserved or diminished brain structure and cognition

Author: Hayek, Dayana, Ziegler, Gabriel, Kleineidam, Luca, Brosseron, Frederic, Nemali, Aditya, Vockert, Niklas, Ravichandran, Kishore A., Betts, Matthew J., Peters, Oliver, Schneider, Luisa-Sophie, Wang, Xiao, Priller, Josef, Altenstein, Slawek, Schneider, Anja, Fliessbach, Klaus, Wiltfang, Jens, Bartels, Claudia, Rostamzadeh, Ayda, Glanz, Wenzel, Buerger, Katharina, Janowitz, Daniel, Perneczky, Robert, Rauchmann, Boris-Stephan, Teipel, Stefan, Kilimann, Ingo, Laske, Christoph, Mengel, David, Synofzik, Matthis, Munk, Matthias H., Spottke, Annika, Roy, Nina, Roeske, Sandra, Kuhn, Elizabeth, Ramirez, Alfredo, Dobisch, Laura, Schmid, Matthias, Berger, Moritz, Wolfsgruber, Steffen, Yakupov, Renat, Hetzer, Stefan, Dechent, Peter, Ewers, Michael, Scheffler, Klaus, Schott, Björn H., Schreiber, Stefanie, Orellana, Adelina, de Rojas, Itziar, Marquié, Marta, Boada, Mercè, Sotolongo, Oscar, González, Pablo García, Puerta, Raquel, Düzel, Emrah, Jessen, Frank, Wagner, Michael, Ruiz, Augustín, Heneka, Michael T., and Maass, Anne
Published: 2024
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2. Fronto-striatal alterations correlate with apathy severity in behavioral variant frontotemporal dementia

Author: Upadhyay, Neeraj, Spottke, Annika, Schneider, Anja, Hoffmann, Daniel C., Frommann, Ingo, Ballarini, Tommaso, Fliessbach, Klaus, Bender, Benjamin, Heekeren, Hauke R., Haynes, John Dylan, Ewers, Michael, Düzel, Emrah, Glanz, Wenzel, Dobisch, Laura, Buerger, Katharina, Janowitz, Daniel, Levin, Johannes, Danek, Adrian, Teipel, Stefan, Kilimann, Ingo, Synofzik, Matthis, Wilke, Carlo, Peters, Oliver, Preis, Lukas, Priller, Josef, Spruth, Eike Jakob, Jessen, Frank, and Boecker, Henning
Published: 2024
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3. Serum IL-6, sAXL, and YKL-40 as systemic correlates of reduced brain structure and function in Alzheimer’s disease: results from the DELCODE study

Author: Brosseron, Frederic, Maass, Anne, Kleineidam, Luca, Ravichandran, Kishore Aravind, Kolbe, Carl-Christian, Wolfsgruber, Steffen, Santarelli, Francesco, Häsler, Lisa M., McManus, Róisín, Ising, Christina, Röske, Sandra, Peters, Oliver, Cosma, Nicoleta-Carmen, Schneider, Luisa-Sophie, Wang, Xiao, Priller, Josef, Spruth, Eike J., Altenstein, Slawek, Schneider, Anja, Fliessbach, Klaus, Wiltfang, Jens, Schott, Björn H., Buerger, Katharina, Janowitz, Daniel, Dichgans, Martin, Perneczky, Robert, Rauchmann, Boris-Stephan, Teipel, Stefan, Kilimann, Ingo, Görß, Doreen, Laske, Christoph, Munk, Matthias H., Düzel, Emrah, Yakupow, Renat, Dobisch, Laura, Metzger, Coraline D., Glanz, Wenzel, Ewers, Michael, Dechent, Peter, Haynes, John Dylan, Scheffler, Klaus, Roy, Nina, Rostamzadeh, Ayda, Spottke, Annika, Ramirez, Alfredo, Mengel, David, Synofzik, Matthis, Jucker, Mathias, Latz, Eicke, Jessen, Frank, Wagner, Michael, and Heneka, Michael T.
Published: 2023
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4. Arterial hypertension and β-amyloid accumulation have spatially overlapping effects on posterior white matter hyperintensity volume: a cross-sectional study

Author: Bernal, Jose, Schreiber, Stefanie, Menze, Inga, Ostendorf, Anna, Pfister, Malte, Geisendörfer, Jonas, Nemali, Aditya, Maass, Anne, Yakupov, Renat, Peters, Oliver, Preis, Lukas, Schneider, Luisa, Herrera, Ana Lucia, Priller, Josef, Spruth, Eike Jakob, Altenstein, Slawek, Schneider, Anja, Fliessbach, Klaus, Wiltfang, Jens, Schott, Björn H., Rostamzadeh, Ayda, Glanz, Wenzel, Buerger, Katharina, Janowitz, Daniel, Ewers, Michael, Perneczky, Robert, Rauchmann, Boris-Stephan, Teipel, Stefan, Kilimann, Ingo, Laske, Christoph, Munk, Matthias H., Spottke, Annika, Roy, Nina, Dobisch, Laura, Dechent, Peter, Scheffler, Klaus, Hetzer, Stefan, Wolfsgruber, Steffen, Kleineidam, Luca, Schmid, Matthias, Berger, Moritz, Jessen, Frank, Wirth, Miranka, Düzel, Emrah, and Ziegler, Gabriel
Published: 2023
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5. Exploring the ATN classification system using brain morphology

Author: Heinzinger, Nils, Maass, Anne, Berron, David, Yakupov, Renat, Peters, Oliver, Fiebach, Jochen, Villringer, Kersten, Preis, Lukas, Priller, Josef, Spruth, Eike Jacob, Altenstein, Slawek, Schneider, Anja, Fliessbach, Klaus, Wiltfang, Jens, Bartels, Claudia, Jessen, Frank, Maier, Franziska, Glanz, Wenzel, Buerger, Katharina, Janowitz, Daniel, Perneczky, Robert, Rauchmann, Boris-Stephan, Teipel, Stefan, Killimann, Ingo, Göerß, Doreen, Laske, Christoph, Munk, Matthias H., Spottke, Annika, Roy, Nina, Heneka, Michael T., Brosseron, Frederic, Dobisch, Laura, Ewers, Michael, Dechent, Peter, Haynes, John Dylan, Scheffler, Klaus, Wolfsgruber, Steffen, Kleineidam, Luca, Schmid, Matthias, Berger, Moritz, Düzel, Emrah, and Ziegler, Gabriel
Published: 2023
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6. Brain reserve contributes to distinguishing preclinical Alzheimer’s stages 1 and 2

Author: Yildirim, Zerrin, Delen, Firuze, Berron, David, Baumeister, Hannah, Ziegler, Gabriel, Schütze, Hartmut, Glanz, Wenzel, Dobisch, Laura, Peters, Oliver, Freiesleben, Silka Dawn, Schneider, Luisa-Sophie, Priller, Josef, Spruth, Eike Jakob, Schneider, Anja, Fliessbach, Klaus, Wiltfang, Jens, Schott, Björn-Hendrik, Meiberth, Dix, Buerger, Katharina, Janowitz, Daniel, Perneczky, Robert, Rauchmann, Boris-Stephan, Teipel, Stefan, Kilimann, Ingo, Laske, Christoph, Munk, Matthias H., Spottke, Annika, Roy, Nina, Heneka, Michael, Brosseron, Frederic, Wagner, Michael, Roeske, Sandra, Ramirez, Alfredo, Ewers, Michael, Dechent, Peter, Hetzer, Stefan, Scheffler, Klaus, Kleineidam, Luca, Wolfsgruber, Steffen, Yakupov, Renat, Schmid, Matthias, Berger, Moritz, Gurvit, Hakan, Jessen, Frank, and Duzel, Emrah
Published: 2023
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7. Fornix fractional anisotropy mediates the association between Mediterranean diet adherence and memory four years later in older adults without dementia

Author: Ruiz-Rizzo, Adriana L., Finke, Kathrin, Damoiseaux, Jessica S., Bartels, Claudia, Buerger, Katharina, Cosma, Nicoleta Carmen, Dechent, Peter, Dobisch, Laura, Ewers, Michael, Fliessbach, Klaus, Frommann, Ingo, Glanz, Wenzel, Goerss, Doreen, Hetzer, Stefan, Incesoy, Enise I., Janowitz, Daniel, Kilimann, Ingo, Laske, Christoph, van Lent, Debora Melo, Munk, Matthias H.J., Peters, Oliver, Priller, Josef, Ramirez, Alfredo, Rostamzadeh, Ayda, Roy, Nina, Scheffler, Klaus, Schneider, Anja, Spottke, Annika, Spruth, Eike Jakob, Teipel, Stefan, Wagner, Michael, Wiltfang, Jens, Yakupov, Renat, Jessen, Frank, Duezel, Emrah, Perneczky, Robert, and Rauchmann, Boris-Stephan
Published: 2024
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8. Improving 3D convolutional neural network comprehensibility via interactive visualization of relevance maps: Evaluation in Alzheimer's disease

Author: Dyrba, Martin, Hanzig, Moritz, Altenstein, Slawek, Bader, Sebastian, Ballarini, Tommaso, Brosseron, Frederic, Buerger, Katharina, Cantré, Daniel, Dechent, Peter, Dobisch, Laura, Düzel, Emrah, Ewers, Michael, Fliessbach, Klaus, Glanz, Wenzel, Haynes, John-Dylan, Heneka, Michael T., Janowitz, Daniel, Keles, Deniz B., Kilimann, Ingo, Laske, Christoph, Maier, Franziska, Metzger, Coraline D., Munk, Matthias H., Perneczky, Robert, Peters, Oliver, Preis, Lukas, Priller, Josef, Rauchmann, Boris, Roy, Nina, Scheffler, Klaus, Schneider, Anja, Schott, Björn H., Spottke, Annika, Spruth, Eike J., Weber, Marc-André, Ertl-Wagner, Birgit, Wagner, Michael, Wiltfang, Jens, Jessen, Frank, and Teipel, Stefan J.
Subjects: Electrical Engineering and Systems Science - Image and Video Processing, Computer Science - Computer Vision and Pattern Recognition
Abstract: Background: Although convolutional neural networks (CNN) achieve high diagnostic accuracy for detecting Alzheimer's disease (AD) dementia based on magnetic resonance imaging (MRI) scans, they are not yet applied in clinical routine. One important reason for this is a lack of model comprehensibility. Recently developed visualization methods for deriving CNN relevance maps may help to fill this gap. We investigated whether models with higher accuracy also rely more on discriminative brain regions predefined by prior knowledge. Methods: We trained a CNN for the detection of AD in N=663 T1-weighted MRI scans of patients with dementia and amnestic mild cognitive impairment (MCI) and verified the accuracy of the models via cross-validation and in three independent samples including N=1655 cases. We evaluated the association of relevance scores and hippocampus volume to validate the clinical utility of this approach. To improve model comprehensibility, we implemented an interactive visualization of 3D CNN relevance maps. Results: Across three independent datasets, group separation showed high accuracy for AD dementia vs. controls (AUC$\geq$0.92) and moderate accuracy for MCI vs. controls (AUC$\approx$0.75). Relevance maps indicated that hippocampal atrophy was considered as the most informative factor for AD detection, with additional contributions from atrophy in other cortical and subcortical regions. Relevance scores within the hippocampus were highly correlated with hippocampal volumes (Pearson's r$\approx$-0.86, p<0.001). Conclusion: The relevance maps highlighted atrophy in regions that we had hypothesized a priori. This strengthens the comprehensibility of the CNN models, which were trained in a purely data-driven manner based on the scans and diagnosis labels., Comment: 24 pages, 9 figures/tables, supplementary material, source code available on GitHub
Published: 2020
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9. Linking early-life bilingualism and cognitive advantage in older adulthood

Author: Ballarini, Tommaso, Kuhn, Elizabeth, Röske, Sandra, Altenstein, Slawek, Bartels, Claudia, Buchholz, Friederike, Buerger, Katharina, Dechent, Peter, Dobisch, Laura, Ewers, Michael, Fliessbach, Klaus, Freiesleben, Silka Dawn, Frommann, Ingo, Gabelin, Tatjana, Glanz, Wenzel, Görß, Doreen, Haynes, John Dylan, Incesoy, Enise I., Janowitz, Daniel, Kilimann, Ingo, Kleineidam, Luca, Kobeleva, Xenia, Laske, Christoph, Lohse, Andrea, Maier, Franziska, Munk, Matthias H., Perneczky, Robert, Peters, Oliver, Priller, Josef, Rauchmann, Boris-Stephan, Roy, Nina, Scheffler, Klaus, Schneider, Anja, Schott, Björn H., Spottke, Annika, Spruth, Eike Jakob, Teipel, Stefan, Wiltfang, Jens, Wolfsgruber, Steffen, Düzel, Emrah, Jessen, Frank, and Wagner, Michael
Published: 2023
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10. Lifelong experiences as a proxy of cognitive reserve moderate the association between connectivity and cognition in Alzheimer's disease

Author: Ersoezlue, Ersin, Rauchmann, Boris-Stephan, Schneider-Axmann, Thomas, Wagner, Michael, Ballarini, Tommaso, Tato, Maia, Utecht, Julia, Kurz, Carolin, Papazov, Boris, Guersel, Selim, Burow, Lena, Koller, Gabriele, Stöcklein, Sophia, Keeser, Daniel, Bartels, Claudia, Brosseron, Frederic, Buerger, Katharina, Cetindag, Arda C., Dechent, Peter, Dobisch, Laura, Ewers, Michael, Fliessbach, Klaus, Frommann, Ingo, Haynes, John D., Heneka, Michael T., Janowitz, Daniel, Kilimann, Ingo, Kleinedam, Luca, Laske, Christoph, Maier, Franziska, Metzger, Coraline D., Munk, Matthias H., Peters, Oliver, Preis, Lukas, Priller, Josef, Ramirez, Alfredo, Roeske, Sandra, Roy, Nina, Scheffler, Klaus, Schneider, Anja, Spottke, Annika, Spruth, Eike J., Teipel, Stefan, Wiltfang, Jens, Wolfsgruber, Steffen, Yakupov, Renat, Duezel, Emrah, Jessen, Frank, and Perneczky, Robert
Published: 2023
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11. 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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12. Machine Learning–Based Perivascular Space Volumetry in Alzheimer Disease

Author: Deike, Katerina, primary, Decker, Andreas, additional, Scheyhing, Paul, additional, Harten, Julia, additional, Zimmermann, Nadine, additional, Paech, Daniel, additional, Peters, Oliver, additional, Freiesleben, Silka D., additional, Schneider, Luisa-Sophie, additional, Preis, Lukas, additional, Priller, Josef, additional, Spruth, Eike, additional, Altenstein, Slawek, additional, Lohse, Andrea, additional, Fliessbach, Klaus, additional, Kimmich, Okka, additional, Wiltfang, Jens, additional, Bartels, Claudia, additional, Hansen, Niels, additional, Jessen, Frank, additional, Rostamzadeh, Ayda, additional, Düzel, Emrah, additional, Glanz, Wenzel, additional, Incesoy, Enise I., additional, Butryn, Michaela, additional, Buerger, Katharina, additional, Janowitz, Daniel, additional, Ewers, Michael, additional, Perneczky, Robert, additional, Rauchmann, Boris-Stephan, additional, Teipel, Stefan, additional, Kilimann, Ingo, additional, Goerss, Doreen, additional, Laske, Christoph, additional, Munk, Matthias H., additional, Spottke, Annika, additional, Roy, Nina, additional, Wagner, Michael, additional, Roeske, Sandra, additional, Heneka, Michael T., additional, Brosseron, Frederic, additional, Ramirez, Alfredo, additional, Dobisch, Laura, additional, Wolfsgruber, Steffen, additional, Kleineidam, Luca, additional, Yakupov, Renat, additional, Stark, Melina, additional, Schmid, Matthias C., additional, Berger, Moritz, additional, Hetzer, Stefan, additional, Dechent, Peter, additional, Scheffler, Klaus, additional, Petzold, Gabor C., additional, Schneider, Anja, additional, Effland, Alexander, additional, and Radbruch, Alexander, additional
Published: 2024
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13. Improving 3D convolutional neural network comprehensibility via interactive visualization of relevance maps: evaluation in Alzheimer’s disease

Author: Dyrba, Martin, Hanzig, Moritz, Altenstein, Slawek, Bader, Sebastian, Ballarini, Tommaso, Brosseron, Frederic, Buerger, Katharina, Cantré, Daniel, Dechent, Peter, Dobisch, Laura, Düzel, Emrah, Ewers, Michael, Fliessbach, Klaus, Glanz, Wenzel, Haynes, John-Dylan, Heneka, Michael T., Janowitz, Daniel, Keles, Deniz B., Kilimann, Ingo, Laske, Christoph, Maier, Franziska, Metzger, Coraline D., Munk, Matthias H., Perneczky, Robert, Peters, Oliver, Preis, Lukas, Priller, Josef, Rauchmann, Boris, Roy, Nina, Scheffler, Klaus, Schneider, Anja, Schott, Björn H., Spottke, Annika, Spruth, Eike J., Weber, Marc-André, Ertl-Wagner, Birgit, Wagner, Michael, Wiltfang, Jens, Jessen, Frank, and Teipel, Stefan J.
Published: 2021
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14. Memorability of photographs in subjective cognitive decline and mild cognitive impairment: Implications for cognitive assessment

Author: Bainbridge, Wilma A., Berron, David, Schütze, Hartmut, Cardenas-Blanco, Arturo, Metzger, Coraline, Dobisch, Laura, Bittner, Daniel, Glanz, Wenzel, Spottke, Annika, Rudolph, Janna, Brosseron, Frederic, Buerger, Katharina, Janowitz, Daniel, Fliessbach, Klaus, Heneka, Michael, Laske, Christoph, Buchmann, Martina, Peters, Oliver, Diesing, Dominik, Li, Siyao, Priller, Josef, Spruth, Eike Jakob, Altenstein, Slawek, Schneider, Anja, Kofler, Barbara, Teipel, Stefan, Kilimann, Ingo, Wiltfang, Jens, Bartels, Claudia, Wolfsgruber, Steffen, Wagner, Michael, Jessen, Frank, Baker, Chris I., and Düzel, Emrah
Published: 2019
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15. Fronto-striatal alterations correlate with apathy severity in behavioral variant frontotemporal dementia

Author: Upadhyay, Neeraj, primary, Spottke, Annika, additional, Schneider, Anja, additional, Hoffmann, Daniel C., additional, Frommann, Ingo, additional, Ballarini, Tommaso, additional, Fliessbach, Klaus, additional, Bender, Benjamin, additional, Heekeren, Hauke R., additional, Haynes, John Dylan, additional, Ewers, Michael, additional, Düzel, Emrah, additional, Glanz, Wenzel, additional, Dobisch, Laura, additional, Buerger, Katharina, additional, Janowitz, Daniel, additional, Levin, Johannes, additional, Danek, Adrian, additional, Teipel, Stefan, additional, Kilimann, Ingo, additional, Synofzik, Matthis, additional, Wilke, Carlo, additional, Peters, Oliver, additional, Preis, Lukas, additional, Priller, Josef, additional, Spruth, Eike Jakob, additional, Jessen, Frank, additional, and Boecker, Henning, additional
Published: 2023
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16. Machine learning‐based classification of Alzheimer's disease and its at‐risk states using personality traits, anxiety, and depression

Author: Waschkies, Konrad F., primary, Soch, Joram, additional, Darna, Margarita, additional, Richter, Anni, additional, Altenstein, Slawek, additional, Beyle, Aline, additional, Brosseron, Frederic, additional, Buchholz, Friederike, additional, Butryn, Michaela, additional, Dobisch, Laura, additional, Ewers, Michael, additional, Fliessbach, Klaus, additional, Gabelin, Tatjana, additional, Glanz, Wenzel, additional, Goerss, Doreen, additional, Gref, Daria, additional, Janowitz, Daniel, additional, Kilimann, Ingo, additional, Lohse, Andrea, additional, Munk, Matthias H., additional, Rauchmann, Boris‐Stephan, additional, Rostamzadeh, Ayda, additional, Roy, Nina, additional, Spruth, Eike Jakob, additional, Dechent, Peter, additional, Heneka, Michael T., additional, Hetzer, Stefan, additional, Ramirez, Alfredo, additional, Scheffler, Klaus, additional, Buerger, Katharina, additional, Laske, Christoph, additional, Perneczky, Robert, additional, Peters, Oliver, additional, Priller, Josef, additional, Schneider, Anja, additional, Spottke, Annika, additional, Teipel, Stefan, additional, Düzel, Emrah, additional, Jessen, Frank, additional, Wiltfang, Jens, additional, Schott, Björn H., additional, and Kizilirmak, Jasmin M., additional
Published: 2023
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17. CSF total tau levels are associated with hippocampal novelty irrespective of hippocampal volume

Author: Düzel, Emrah, Berron, David, Schütze, Hartmut, Cardenas-Blanco, Arturo, Metzger, Coraline, Betts, Matthew, Ziegler, Gabriel, Chen, Yi, Dobisch, Laura, Bittner, Daniel, Glanz, Wenzel, Reuter, Martin, Spottke, Annika, Rudolph, Janna, Brosseron, Frederic, Buerger, Katharina, Janowitz, Daniel, Fliessbach, Klaus, Heneka, Michael, Laske, Christoph, Buchmann, Martina, Nestor, Peter, Peters, Oliver, Diesing, Dominik, Li, Siyao, Priller, Josef, Spruth, Eike Jakob, Altenstein, Slawek, Ramirez, Alfredo, Schneider, Anja, Kofler, Barbara, Speck, Oliver, Teipel, Stefan, Kilimann, Ingo, Dyrba, Martin, Wiltfang, Jens, Bartels, Claudia, Wolfsgruber, Steffen, Wagner, Michael, and Jessen, Frank
Published: 2018
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18. Altered limbic functional connectivity in individuals with subjective cognitive decline: Converging and diverging findings across Chinese and German cohorts.

Author: Jiang, Xueyan, Hu, Xiaochen, Daamen, Marcel, Wang, Xiaoqi, Fan, Chunqiu, Meiberth, Dix, Spottke, Annika, Roeske, Sandra, Fliessbach, Klaus, Spruth, Eike Jakob, Altenstein, Slawek, Lohse, Andrea, Hansen, Niels, Glanz, Wenzel, Incesoy, Enise I., Dobisch, Laura, Janowitz, Daniel, Rauchmann, Boris‐Stephan, Ramirez, Alfredo, and Kilimann, Ingo
Abstract: INTRODUCTION: It remains unclear whether functional brain networks are consistently altered in individuals with subjective cognitive decline (SCD) of diverse ethnic and cultural backgrounds and whether the network alterations are associated with an amyloid burden. METHODS: Cross‐sectional resting‐state functional magnetic resonance imaging connectivity (FC) and amyloid‐positron emission tomography (PET) data from the Chinese Sino Longitudinal Study on Cognitive Decline and German DZNE Longitudinal Cognitive Impairment and Dementia cohorts were analyzed. RESULTS: Limbic FC, particularly hippocampal connectivity with right insula, was consistently higher in SCD than in controls, and correlated with SCD‐plus features. Smaller SCD subcohorts with PET showed inconsistent amyloid positivity rates and FC–amyloid associations across cohorts. DISCUSSION: Our results suggest an early adaptation of the limbic network in SCD, which may reflect increased awareness of cognitive decline, irrespective of amyloid pathology. Different amyloid positivity rates may indicate a heterogeneous underlying etiology in Eastern and Western SCD cohorts when applying current research criteria. Future studies should identify culture‐specific features to enrich preclinical Alzheimer's disease in non‐Western populations. Highlights: Common limbic hyperconnectivity across Chinese and German subjective cognitive decline (SCD) cohorts was observed.Limbic hyperconnectivity may reflect awareness of cognition, irrespective of amyloid load.Further cross‐cultural harmonization of SCD regarding Alzheimer's disease pathology is required. [ABSTRACT FROM AUTHOR]
Published: 2023
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19. Cerebral small vessel disease burden and cognitive and functional outcomes after stroke: A multicenter prospective cohort study

Author: Georgakis, Marios K, Fang, Rong, Kerti, Lucia, Ikenberg, Benno, Bernkopf, Kathleen, Poppert, Holger, Glanz, Wenzel, Perosa, Valentina, Janowitz, Daniel, Wagner, Michael, Neumann, Katja, Speck, Oliver, Düring, Marco, Dobisch, Laura, Düzel, Emrah, Gesierich, Benno, Dewenter, Anna, Spottke, Annika, Waegemann, Karin, Görtler, Michael, Wunderlich, Silke, Endres, Matthias, Zerr, Inga, Wollenweber, Frank A, Petzold, Gabor, Dichgans, Martin, Investigators, DEMDAS, Bode, Felix J, Stoesser, Sebastian, Kindlein, Christine, Hermann, Peter, Liman, Thomas G, and Nolte, Christian H
Subjects: RESEARCH ARTICLE, RESEARCH ARTICLES, cerebral small vessel disease, cognitive impairment, functional outcome, prediction, stroke, Epidemiology, Health Policy, Magnetic Resonance Imaging, ddc, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Cognition, Developmental Neuroscience, pathology [Stroke], Humans, pathology [Cerebral Small Vessel Diseases], complications [Stroke], ddc:610, Prospective Studies, Neurology (clinical), Geriatrics and Gerontology, complications [Cognitive Dysfunction]
Abstract: It remains unknown whether the global small vessel disease (SVD) burden predicts post-stroke outcomes.In a prospective multicenter study of 666 ischemic and hemorrhagic stroke patients, we quantified magnetic resonance imaging (MRI)-based SVD markers (lacunes, white matter hyperintensities, microbleeds, perivascular spaces) and explored associations with 6- and 12-month cognitive (battery of 15 neuropsychological tests) and functional (modified Rankin scale) outcomes.A global SVD score (range 0-4) was associated with cognitive impairment; worse performance in executive function, attention, language, and visuospatial ability; and worse functional outcome across a 12-month follow-up. Although the global SVD score did not improve prediction, individual SVD markers, assessed across their severity range, improved the calibration, discrimination, and reclassification of predictive models including demographic, clinical, and other imaging factors.SVD presence and severity are associated with worse cognitive and functional outcomes 12 months after stroke. Assessing SVD severity may aid prognostication for stroke patients.In a multi-center cohort, we explored associations of small vessel disease (SVD) burden with stroke outcomes. SVD burden associates with post-stroke cognitive and functional outcomes. A currently used score of SVD burden does not improve the prediction of poor outcomes. Assessing the severity of SVD lesions adds predictive value beyond known predictors. To add predictive value in assessing SVD in stroke patients, SVD burden scores should integrate lesion severity.
Published: 2022

20. 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

21. 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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22. Cortical Amyloid Burden Relates to Basal Forebrain Volume in Subjective Cognitive Decline

Author: Daamen, Marcel, Scheef, Lukas, Li, Shumei, Grothe, Michel J., Gaertner, Florian C., Buchert, Ralph, Buerger, Katharina, Dobisch, Laura, Drzezga, Alexander, Essler, Markus, Ewers, Michael, Fliessbach, Klaus, Herrera Meléndez, Ana Lucía, Hetzer, Stefan, Janowitz, Daniel, Kilimann, Ingo, Krause, Bernd Joachim, Lange, Catharina, Laske, Christoph, Munk, Matthias H., Peters, Oliver, Priller, Josef, Ramírez, Alfredo, Reimold, Matthias, Rominger, Axel, Rostamzadeh, Ayda, Roeske, Sandra, Roy, Nina, Scheffler, Klaus, Schneider, Anja, Spottke, Annika, Spruth, Eike Jakob, Teipel, Stefan J., Wagner, Michael, Düzel, Emrah, Jessen, Frank, Boecker, Henning, DELCODE Study Group, Daamen, Marcel, Scheef, Lukas, Li, Shumei, Grothe, Michel J., Gaertner, Florian C., Buchert, Ralph, Buerger, Katharina, Dobisch, Laura, Drzezga, Alexander, Essler, Markus, Ewers, Michael, Fliessbach, Klaus, Herrera Meléndez, Ana Lucía, Hetzer, Stefan, Janowitz, Daniel, Kilimann, Ingo, Krause, Bernd Joachim, Lange, Catharina, Laske, Christoph, Munk, Matthias H., Peters, Oliver, Priller, Josef, Ramírez, Alfredo, Reimold, Matthias, Rominger, Axel, Rostamzadeh, Ayda, Roeske, Sandra, Roy, Nina, Scheffler, Klaus, Schneider, Anja, Spottke, Annika, Spruth, Eike Jakob, Teipel, Stefan J., Wagner, Michael, Düzel, Emrah, Jessen, Frank, Boecker, Henning, and DELCODE Study Group
Abstract: Background: Atrophy of cholinergic basal forebrain (BF) nuclei is a frequent finding in magnetic resonance imaging (MRI) volumetry studies that examined patients with prodromal or clinical Alzheimer’s disease (AD), but less clear for individuals in earlier stages of the clinical AD continuum. Objective: To examine BF volume reductions in subjective cognitive decline (SCD) participants with AD pathologic changes. Methods: The present study compared MRI-based BF volume measurements in age- and sex-matched samples of N = 24 amyloid-positive and N = 24 amyloid-negative SCD individuals, based on binary visual ratings of Florbetaben positron emission tomography (PET) measurements. Additionally, we assessed associations of BF volume with cortical amyloid burden, based on semiquantitative Centiloid (CL) analyses. Results: Group differences approached significance for BF total volume (p = 0.061) and the Ch4 subregion (p = 0.059) only, showing the expected relative volume reductions for the amyloid-positive subgroup. There were also significant inverse correlations between BF volumes and CL values, which again were most robust for BF total volume and the Ch4 subregion. Conclusions: The results are consistent with the hypothesis that amyloid-positive SCD individuals, which are considered to represent a transitional stage on the clinical AD continuum, already show incipient alterations of BF integrity. The negative association with a continuous measure of cortical amyloid burden also suggests that this may reflect an incremental process. Yet, further research is needed to evaluate whether BF changes already emerge at “grey zone” levels of amyloid accumulation, before amyloidosis is reliably detected by PET visual readings.
Published: 2023

23. Which features of subjective cognitive decline are related to amyloid pathology? Findings from the DELCODE study

Author: Miebach, Lisa, Wolfsgruber, Steffen, Polcher, Alexandra, Peters, Oliver, Menne, Felix, Luther, Katja, Incesoy, Enise, Priller, Josef, Spruth, Eike, Altenstein, Slawek, Buerger, Katharina, Catak, Cihan, Janowitz, Daniel, Perneczky, Robert, Utecht, Julia, Laske, Christoph, Buchmann, Martina, Schneider, Anja, Fliessbach, Klaus, Kalbhen, Pascal, Heneka, Michael T., Brosseron, Frederic, Spottke, Annika, Roy, Nina, Teipel, Stefan J., Kilimann, Ingo, Wiltfang, Jens, Bartels, Claudia, Düzel, Emrah, Dobisch, Laura, Metzger, Coraline, Meiberth, Dix, Ramirez, Alfredo, Jessen, Frank, and Wagner, Michael
Published: 2019
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24. Long-term environmental enrichment is associated with better fornix microstructure in older adults.

Author: Klimecki, Olga M., Liebscher, Maxie, Gaubert, Malo, Hayek, Dayana, Zarucha, Alexis, Dyrba, Martin, Bartels, Claudia, Buerger, Katharina, Butryn, Michaela, Dechent, Peter, Dobisch, Laura, Ewers, Michael, Fliessbach, Klaus, Freiesleben, Silka Dawn, Glanz, Wenzel, Hetzer, Stefan, Janowitz, Daniel, Kilimann, Ingo, Kleineidam, Luca, and Laske, Christoph
Subjects: ALZHEIMER'S disease prevention, BRAIN physiology, LEISURE, STATISTICS, CONFIDENCE intervals, CROSS-sectional method, MAGNETIC resonance imaging, DESCRIPTIVE statistics, CHI-squared test, RESEARCH funding, DATA analysis software, COMPUTER-assisted image analysis (Medicine), DATA analysis, LONGITUDINAL method, OLD age
Abstract: Background: Sustained environmental enrichment (EE) through a variety of leisure activities may decrease the risk of developing Alzheimer’s disease. This cross-sectional cohort study investigated the association between long-term EE in young adulthood through middle life and microstructure of fiber tracts associated with the memory system in older adults. Methods: N = 201 cognitively unimpaired participants (≥ 60 years of age) from the DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE) baseline cohort were included. Two groups of participants with higher (n = 104) or lower (n = 97) long-term EE were identified, using the self-reported frequency of diverse physical, intellectual, and social leisure activities between the ages 13 to 65. White matter (WM) microstructure was measured by fractional anisotropy (FA) and mean diffusivity (MD) in the fornix, uncinate fasciculus, and parahippocampal cingulum using diffusion tensor imaging. Long-term EE groups (lower/higher) were compared with adjustment for potential confounders, such as education, crystallized intelligence, and socio-economic status. Results: Reported participation in higher long-term EE was associated with greater fornix microstructure, as indicated by higher FA (standardized β = 0.117, p = 0.033) and lower MD (β = −0.147, p = 0.015). Greater fornix microstructure was indirectly associated (FA: unstandardized B = 0.619, p = 0.038; MD: B = −0.035, p = 0.026) with better memory function through higher long-term EE. No significant effects were found for the other WM tracts. Conclusion: Our findings suggest that sustained participation in a greater variety of leisure activities relates to preserved WM microstructure in the memory system in older adults. This could be facilitated by the multimodal stimulation associated with the engagement in a physically, intellectually, and socially enriched lifestyle. Longitudinal studies will be needed to support this assumption. [ABSTRACT FROM AUTHOR]
Published: 2023
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25. 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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26. Machine learning-based classification of Alzheimer’s disease and its at-risk states using personality traits, anxiety, and depression

Author: Waschkies, Konrad F., primary, Soch, Joram, additional, Darna, Margarita, additional, Richter, Anni, additional, Altenstein, Slawek, additional, Beyle, Aline, additional, Brosseron, Frederic, additional, Buchholz, Friederike, additional, Butryn, Michaela, additional, Dobisch, Laura, additional, Ewers, Michael, additional, Fliessbach, Klaus, additional, Gabelin, Tatjana, additional, Glanz, Wenzel, additional, Goerss, Doreen, additional, Gref, Daria, additional, Janowitz, Daniel, additional, Kilimann, Ingo, additional, Lohse, Andrea, additional, Munk, Matthias H., additional, Rauchmann, Boris-Stephan, additional, Rostamzadeh, Ayda, additional, Roy, Nina, additional, Spruth, Eike Jakob, additional, Dechent, Peter, additional, Heneka, Michael T., additional, Hetzer, Stefan, additional, Ramirez, Alfredo, additional, Scheffler, Klaus, additional, Buerger, Katharina, additional, Laske, Christoph, additional, Perneczky, Robert, additional, Peters, Oliver, additional, Priller, Josef, additional, Schneider, Anja, additional, Spottke, Annika, additional, Teipel, Stefan, additional, Düzel, Emrah, additional, Jessen, Frank, additional, Wiltfang, Jens, additional, Schott, Björn H., additional, and Kizilirmak, Jasmin M., additional
Published: 2022
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27. Performance evaluation of automated white matter hyperintensity segmentation algorithms in a multicenter cohort on cognitive impairment and dementia

Author: Gaubert, Malo, Dell'Orco, Andrea, Lange, Catharina, Garnier-Crussard, Antoine, Zimmermann, Isabella, Dyrba, Martin, Duering, Marco, Ziegler, Gabriel, Peters, Oliver, Preis, Lukas, Priller, Josef, Spruth, Eike Jakob, Schneider, Anja, Fliessbach, Klaus, Wiltfang, Jens, Schott, Björn H, Maier, Franziska, Glanz, Wenzel, Buerger, Katharina, Janowitz, Daniel, Perneczky, Robert, Rauchmann, Boris-Stephan, Teipel, Stefan, Kilimann, Ingo, Laske, Christoph, Munk, Matthias H, Spottke, Annika, Roy, Nina, Dobisch, Laura, Ewers, Michael, Dechent, Peter, Haynes, John Dylan, Scheffler, Klaus, Düzel, Emrah, Jessen, Frank, and Wirth, Miranka
Subjects: Psychiatry and Mental health, evaluation, aging, FLAIR, deep learning, ddc:610, Alzheimer’s disease, Psychiatry, white matter hyperintensities segmentation, Alzheimer's disease, ddc
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

28. A Residual Marker of Cognitive Reserve Is Associated with Resting-State Intrinsic Functional Connectivity Along the Alzheimer's Disease Continuum

Author: Ersoezlue, Ersin, Perneczky, Robert, Keeser, Daniel, Papazov, Boris, Totzke, Marie, Ballarini, Tommaso, Brosseron, Frederic, Buerger, Katharina, Dechent, Peter, Dobisch, Laura, Ewers, Michael, Fliessbach, Klaus, Tato, Maia, Glanz, Wenzel, Haynes, John Dylan, Heneka, Michael T, Janowitz, Daniel, Kilimann, Ingo, Kleineidam, Luca, Laske, Christoph, Maier, Franziska, Munk, Matthias H, Peters, Oliver, Utecht, Julia, Priller, Josef, Ramirez, Alfredo, Roeske, Sandra, Roy, Nina, Scheffler, Klaus, Schneider, Anja, Schott, Björn H, Spottke, Annika, Spruth, Eike J, Teipel, Stefan, Kurz, Carolin, Unterfeld, Chantal, Wagner, Michael, Wang, Xiao, Wiltfang, Jens, Wolfsgruber, Steffen, Yakupov, Renat, Duezel, Emrah, Jessen, Frank, Rauchmann, Boris-Stephan, group, DELCODE study, Häckert, Jan, Guersel, Selim, Burow, Lena, Koller, Gabriele, and Stoecklein, Sophia
Subjects: cognition, General Neuroscience, resting-state functional connectivity, General Medicine, cognitive reserve, Magnetic Resonance Imaging, Psychiatry and Mental health, Clinical Psychology, pathology [Alzheimer Disease], intrinsic network connectivity, Neural Pathways, Humans, functional MRI, ddc:610, Geriatrics and Gerontology, Nerve Net, diagnostic imaging [Brain], Alzheimer’s disease
Abstract: Background: Cognitive reserve (CR) explains inter-individual differences in the impact of the neurodegenerative burden on cognitive functioning. A residual model was proposed to estimate CR more accurately than previous measures. However, associations between residual CR markers (CRM) and functional connectivity (FC) remain unexplored. Objective: To explore the associations between the CRM and intrinsic network connectivity (INC) in resting-state networks along the neuropathological-continuum of Alzheimer’s disease (ADN). Methods: Three hundred eighteen participants from the DELCODE cohort were stratified using cerebrospinal fluid biomarkers according to the A(myloid-β)/T(au)/N(eurodegeneration) classification. CRM was calculated utilizing residuals obtained from a multilinear regression model predicting cognition from markers of disease burden. Using an independent component analysis in resting-state fMRI data, we measured INC of resting-state networks, i.e., default mode network (DMN), frontoparietal network (FPN), salience network (SAL), and dorsal attention network. The associations of INC with a composite memory score and CRM and the associations of CRM with the seed-to-voxel functional connectivity of memory-related were tested in general linear models. Results: CRM was positively associated with INC in the DMN in the entire cohort. The A+T+N+ group revealed an anti-correlation between the SAL and the DMN. Furthermore, CRM was positively associated with anti-correlation between memory-related regions in FPN and DMN in ADN and A+T/N+. Conclusion: Our results provide evidence that INC is associated with CRM in ADN defined as participants with amyloid pathology with or without cognitive symptoms, suggesting that the neural correlates of CR are mirrored in network FC in resting-state.
Published: 2023

29. Cholinergic white matter pathways along the Alzheimer's disease continuum

Author: Nemy, Milan, primary, Dyrba, Martin, additional, Brosseron, Frederic, additional, Buerger, Katharina, additional, Dechent, Peter, additional, Dobisch, Laura, additional, Ewers, Michael, additional, Fliessbach, Klaus, additional, Glanz, Wenzel, additional, Goerss, Doreen, additional, Heneka, Michael T, additional, Hetzer, Stefan, additional, Incesoy, Enise I, additional, Janowitz, Daniel, additional, Kilimann, Ingo, additional, Laske, Christoph, additional, Maier, Franziska, additional, Munk, Matthias H, additional, Perneczky, Robert, additional, Peters, Oliver, additional, Preis, Lukas, additional, Priller, Josef, additional, Rauchmann, Boris-Stephan, additional, Röske, Sandra, additional, Roy, Nina, additional, Scheffler, Klaus, additional, Schneider, Anja, additional, Schott, Björn H, additional, Spottke, Annika, additional, Spruth, Eike J, additional, Wagner, Michael, additional, Wiltfang, Jens, additional, Yakupov, Renat, additional, Eriksdotter, Maria, additional, Westman, Eric, additional, Stepankova, Olga, additional, Vyslouzilova, Lenka, additional, Düzel, Emrah, additional, Jessen, Frank, additional, Teipel, Stefan J, additional, and Ferreira, Daniel, additional
Published: 2022
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30. Arterial hypertension and β-amyloid accumulation have spatially overlapping effects on posterior white matter hyperintensity volume: A cross-sectional study

Author: Bernal, Jose, primary, Schreiber, Stefanie, additional, Menze, Inga, additional, Ostendorf, Anna, additional, Pfister, Malte, additional, Geisendörfer, Jonas, additional, Nemali, Aditya, additional, Maass, Anne, additional, Yakupov, Renat, additional, Peters, Oliver, additional, Preis, Lukas, additional, Schneider, Luisa, additional, Herrera, Ana Lucia, additional, Priller, Josef, additional, Spruth, Eike Jakob, additional, Altenstein, Slawek, additional, Schneider, Anja, additional, Fliessbach, Klaus, additional, Wiltfang, Jens, additional, Schott, Björn H., additional, Rostamzadeh, Ayda, additional, Glanz, Wenzel, additional, Buerger, Katharina, additional, Janowitz, Daniel, additional, Ewers, Michael, additional, Perneczky, Robert, additional, Rauchmann, Boris-Stephan, additional, Teipel, Stefan, additional, Kilimann, Ingo, additional, Laske, Christoph, additional, Munk, Matthias H., additional, Spottke, Annika, additional, Roy, Nina, additional, Dobisch, Laura, additional, Dechent, Peter, additional, Scheffler, Klaus, additional, Hetzer, Stefan, additional, Wolfsgruber, Steffen, additional, Kleineidam, Luca, additional, Schmid, Matthias, additional, Berger, Moritz, additional, Jessen, Frank, additional, Wirth, Miranka, additional, Düzel, Emrah, additional, and Ziegler, Gabriel, additional
Published: 2022
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31. Musical Activity During Life Is Associated With Multi-Domain Cognitive and Brain Benefits in Older Adults

Author: Böttcher, Adriana, primary, Zarucha, Alexis, additional, Köbe, Theresa, additional, Gaubert, Malo, additional, Höppner, Angela, 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, Frommann, Ingo, additional, Haynes, John Dylan, additional, Janowitz, Daniel, additional, Kilimann, Ingo, additional, Kleineidam, Luca, additional, Laske, Christoph, additional, Maier, Franziska, additional, Metzger, Coraline, additional, Munk, Matthias H. J., additional, Perneczky, Robert, additional, Peters, Oliver, additional, Priller, Josef, additional, Rauchmann, Boris-Stephan, additional, Roy, Nina, additional, Scheffler, Klaus, additional, Schneider, Anja, additional, Spottke, Annika, additional, Teipel, Stefan J., additional, Wiltfang, Jens, additional, Wolfsgruber, Steffen, additional, Yakupov, Renat, additional, Düzel, Emrah, additional, Jessen, Frank, additional, Röske, Sandra, additional, Wagner, Michael, additional, Kempermann, Gerd, additional, and Wirth, Miranka, additional
Published: 2022
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32. Cholinergic white matter pathways along the Alzheimer's disease continuum.

Author: Nemy, Milan, Dyrba, Martin, Brosseron, Frederic, Buerger, Katharina, Dechent, Peter, Dobisch, Laura, Ewers, Michael, Fliessbach, Klaus, Glanz, Wenzel, Goerss, Doreen, Heneka, Michael T, Hetzer, Stefan, Incesoy, Enise I, Janowitz, Daniel, Kilimann, Ingo, Laske, Christoph, Maier, Franziska, Munk, Matthias H, Perneczky, Robert, and Peters, Oliver
Subjects: ALZHEIMER'S disease, WHITE matter (Nerve tissue), CHOLINERGIC mechanisms, MILD cognitive impairment, COGNITION disorders, RECEIVER operating characteristic curves
Abstract: Previous studies have shown that the cholinergic nucleus basalis of Meynert and its white matter projections are affected in Alzheimer's disease dementia and mild cognitive impairment. However, it is still unknown whether these alterations can be found in individuals with subjective cognitive decline, and whether they are more pronounced than changes found in conventional brain volumetric measurements. To address these questions, we investigated microstructural alterations of two major cholinergic pathways in individuals along the Alzheimer's disease continuum using an in vivo model of the human cholinergic system based on neuroimaging. We included 402 participants (52 Alzheimer's disease, 66 mild cognitive impairment, 172 subjective cognitive decline and 112 healthy controls) from the Deutsches Zentrum für Neurodegenerative Erkrankungen Longitudinal Cognitive Impairment and Dementia Study. We modelled the cholinergic white matter pathways with an enhanced diffusion neuroimaging pipeline that included probabilistic fibre-tracking methods and prior anatomical knowledge. The integrity of the cholinergic white matter pathways was compared between stages of the Alzheimer's disease continuum, in the whole cohort and in a CSF amyloid-beta stratified subsample. The discriminative power of the integrity of the pathways was compared to the conventional volumetric measures of hippocampus and nucleus basalis of Meynert, using a receiver operating characteristics analysis. A multivariate model was used to investigate the role of these pathways in relation to cognitive performance. We found that the integrity of the cholinergic white matter pathways was significantly reduced in all stages of the Alzheimer's disease continuum, including individuals with subjective cognitive decline. The differences involved posterior cholinergic white matter in the subjective cognitive decline stage and extended to anterior frontal white matter in mild cognitive impairment and Alzheimer's disease dementia stages. Both cholinergic pathways and conventional volumetric measures showed higher predictive power in the more advanced stages of the disease, i.e. mild cognitive impairment and Alzheimer's disease dementia. In contrast, the integrity of cholinergic pathways was more informative in distinguishing subjective cognitive decline from healthy controls, as compared with the volumetric measures. The multivariate model revealed a moderate contribution of the cholinergic white matter pathways but not of volumetric measures towards memory tests in the subjective cognitive decline and mild cognitive impairment stages. In conclusion, we demonstrated that cholinergic white matter pathways are altered already in subjective cognitive decline individuals, preceding the more widespread alterations found in mild cognitive impairment and Alzheimer's disease. The integrity of the cholinergic pathways identified the early stages of Alzheimer's disease better than conventional volumetric measures such as hippocampal volume or volume of cholinergic nucleus basalis of Meynert. [ABSTRACT FROM AUTHOR]
Published: 2023
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33. Exploring the ATN classification system using Brain Morphology

Author: Heinzinger, Nils, primary, Maass, Anne, additional, Berron, David, additional, Yakupov, Renat, additional, Peters, Oliver, additional, Fiebach, Jochen, additional, Villringer, Kersten, additional, Preis, Lukas, additional, Priller, Josef, additional, Spruth, Eike Jacob, additional, Altenstein, Slawek, additional, Schneider, Anja, additional, Fliessbach, Klaus, additional, Wiltfang, Jens, additional, Bartels, Claudia, additional, Jessen, Frank, additional, Maier, Franziska, additional, Glanz, Wenzel, additional, Buerger, Katharina, additional, Janowitz, Daniel, additional, Dichgans, Martin, additional, Perneczky, Robert, additional, Rauchmann, Boris-Stephan, additional, Teipel, Stefan, additional, Killimann, Ingo, additional, Göerß, Doreen, additional, Laske, Christoph, additional, Munk, Matthias H., additional, Spottke, Annika, additional, Roy, Nina, additional, Heneka, Michael T., additional, Brosseron, Frederic, additional, Dobisch, Laura, additional, Ewers, Michael, additional, Dechent, Peter, additional, Haynes, John Dylan, additional, Scheffler, Klaus, additional, Wolfsgruber, Steffen, additional, Kleineidam, Luca, additional, Schmid, Matthias, additional, Berger, Moritz, additional, Düzel, Emrah, additional, and Ziegler, Gabriel, additional
Published: 2022
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34. Soluble TAM receptors sAXL and sTyro3 predict structural and functional protection in Alzheimer's disease.

Author: Brosseron, Frederic, Maass, Anne, Kleineidam, Luca, Ravichandran, Kishore Aravind, González, Pablo García, McManus, Róisín M., Ising, Christina, Santarelli, Francesco, Kolbe, Carl-Christian, Häsler, Lisa M., Wolfsgruber, Steffen, Marquié, Marta, Boada, Mercè, Orellana, Adelina, de Rojas, Itziar, Röske, Sandra, Peters, Oliver, Cosma, Nicoleta-Carmen, Cetindag, Arda, Wang, Xiao, Priller, Josef, Spruth, Eike J., Altenstein, Slawek, Schneider, Anja, Fliessbach, Klaus, Wiltfang, Jens, Schott, Björn H., Bürger, Katharina, Janowitz, Daniel, Dichgans, Martin, Perneczky, Robert, Rauchmann, Boris-Stephan, Teipel, Stefan, Kilimann, Ingo, Goerss, Doreen, Laske, Christoph, Munk, Matthias H., Düzel, Emrah, Yakupov, Renat, Dobisch, Laura, Metzger, Coraline D., Glanz, Wenzel, Ewers, Michael, Dechent, Peter, Haynes, John Dylan, Scheffler, Klaus, Roy, Nina, Rostamzadeh, Ayda, Teunissen, Charlotte E., Marchant, Natalie L., Spottke, Annika, Jucker, Mathias, Latz, Eicke, Wagner, Michael, Mengel, David, Synofzik, Matthis, Jessen, Frank, Ramirez, Alfredo, Ruiz, Agustín, Heneka, Michael, Brosseron, Frederic, Maass, Anne, Kleineidam, Luca, Ravichandran, Kishore Aravind, González, Pablo García, McManus, Róisín M., Ising, Christina, Santarelli, Francesco, Kolbe, Carl-Christian, Häsler, Lisa M., Wolfsgruber, Steffen, Marquié, Marta, Boada, Mercè, Orellana, Adelina, de Rojas, Itziar, Röske, Sandra, Peters, Oliver, Cosma, Nicoleta-Carmen, Cetindag, Arda, Wang, Xiao, Priller, Josef, Spruth, Eike J., Altenstein, Slawek, Schneider, Anja, Fliessbach, Klaus, Wiltfang, Jens, Schott, Björn H., Bürger, Katharina, Janowitz, Daniel, Dichgans, Martin, Perneczky, Robert, Rauchmann, Boris-Stephan, Teipel, Stefan, Kilimann, Ingo, Goerss, Doreen, Laske, Christoph, Munk, Matthias H., Düzel, Emrah, Yakupov, Renat, Dobisch, Laura, Metzger, Coraline D., Glanz, Wenzel, Ewers, Michael, Dechent, Peter, Haynes, John Dylan, Scheffler, Klaus, Roy, Nina, Rostamzadeh, Ayda, Teunissen, Charlotte E., Marchant, Natalie L., Spottke, Annika, Jucker, Mathias, Latz, Eicke, Wagner, Michael, Mengel, David, Synofzik, Matthis, Jessen, Frank, Ramirez, Alfredo, Ruiz, Agustín, and Heneka, Michael
Abstract: There is an urgent need to improve the understanding of neuroinflammation in Alzheimer's disease (AD). We analyzed cerebrospinal fluid inflammatory biomarker correlations to brain structural volume and longitudinal cognitive outcomes in the DELCODE study and in a validation cohort of the F.ACE Alzheimer Center Barcelona. We investigated whether respective biomarker changes are evident before onset of cognitive impairment. YKL-40; sTREM2; sAXL; sTyro3; MIF; complement factors C1q, C4, and H; ferritin; and ApoE protein were elevated in pre-dementia subjects with pathological levels of tau or other neurodegeneration markers, demonstrating tight interactions between inflammation and accumulating neurodegeneration even before onset of symptoms. Intriguingly, higher levels of ApoE and soluble TAM receptors sAXL and sTyro3 were related to larger brain structure and stable cognitive outcome at follow-up. Our findings indicate a protective mechanism relevant for intervention strategies aiming to regulate neuroinflammation in subjects with no or subjective symptoms but underlying AD pathology profile.
Published: 2022

35. Musical Activity During Life Is Associated With Multi-Domain Cognitive and Brain Benefits in Older Adults

Author: Böttcher, Adriana, Zarucha, Alexis, Köbe, Theresa, Gaubert, Malo, Höppner, Angela, Altenstein, Slawek, Bartels, Claudia, Buerger, Katharina, Dechent, Peter, Dobisch, Laura, Ewers, Michael, Fliessbach, Klaus, Freiesleben, Silka Dawn, Frommann, Ingo, Haynes, John Dylan, Janowitz, Daniel, Kilimann, Ingo, Kleineidam, Luca, Laske, Christoph, Maier, Franziska, Metzger, Coraline, Munk, Matthias H. J., Perneczky, Robert, Peters, Oliver, Priller, Josef, Rauchmann, Boris-Stephan, Roy, Nina, Scheffler, Klaus, Schneider, Anja, Spottke, Annika, Teipel, Stefan J., Wiltfang, Jens, Wolfsgruber, Steffen, Yakupov, Renat, Düzel, Emrah, Jessen, Frank, Röske, Sandra, Wagner, Michael, Kempermann, Gerd, Wirth, Miranka, Böttcher, Adriana, Zarucha, Alexis, Köbe, Theresa, Gaubert, Malo, Höppner, Angela, Altenstein, Slawek, Bartels, Claudia, Buerger, Katharina, Dechent, Peter, Dobisch, Laura, Ewers, Michael, Fliessbach, Klaus, Freiesleben, Silka Dawn, Frommann, Ingo, Haynes, John Dylan, Janowitz, Daniel, Kilimann, Ingo, Kleineidam, Luca, Laske, Christoph, Maier, Franziska, Metzger, Coraline, Munk, Matthias H. J., Perneczky, Robert, Peters, Oliver, Priller, Josef, Rauchmann, Boris-Stephan, Roy, Nina, Scheffler, Klaus, Schneider, Anja, Spottke, Annika, Teipel, Stefan J., Wiltfang, Jens, Wolfsgruber, Steffen, Yakupov, Renat, Düzel, Emrah, Jessen, Frank, Röske, Sandra, Wagner, Michael, Kempermann, Gerd, and Wirth, Miranka
Abstract: Regular musical activity as a complex multimodal lifestyle activity is proposed to be protective against age-related cognitive decline and Alzheimer’s disease. This cross-sectional study investigated the association and interplay between musical instrument playing during life, multi-domain cognitive abilities and brain morphology in older adults (OA) from the DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE) study. Participants reporting having played a musical instrument across three life periods (n = 70) were compared to controls without a history of musical instrument playing (n = 70), well-matched for reserve proxies of education, intelligence, socioeconomic status and physical activity. Participants with musical activity outperformed controls in global cognition, working memory, executive functions, language, and visuospatial abilities, with no effects seen for learning and memory. The musically active group had greater gray matter volume in the somatosensory area, but did not differ from controls in higher-order frontal, temporal, or hippocampal volumes. However, the association between gray matter volume in distributed frontal-to-temporal regions and cognitive abilities was enhanced in participants with musical activity compared to controls. We show that playing a musical instrument during life relates to better late-life cognitive abilities and greater brain capacities in OA. Musical activity may serve as a multimodal enrichment strategy that could help preserve cognitive and brain health in late life. Longitudinal and interventional studies are needed to support this notion.
Published: 2022

36. Association of Cholinergic Basal Forebrain Volume and Functional Connectivity with Markers of Inflammatory Response in the Alzheimer's Disease Spectrum

Author: Teipel, Stefan J., Dyrba, Martin, Ballarini, Tommaso, Brosseron, Frederic, Bruno, Davide, Buerger, Katharina, Cosma, Nicoleta-Carmen, Dechent, Peter, Dobisch, Laura, Duezel, Emrah, Ewers, Michael, Fliessbach, Klaus, Haynes, John D., Janowitz, Daniel, Kilimann, Ingo, Laske, Christoph, Maier, Franziska, Metzger, Coraline D., Munk, Matthias H., Peters, Oliver, Pomara, Nunzio, Preis, Lukas, Priller, Josef, Ramirez, Alfredo, Roy, Nina, Scheffler, Klaus, Schneider, Anja, Schott, Bjoern H., Spottke, Annika, Spruth, Eike J., Wagner, Michael, Wiltfang, Jens, Jessen, Frank, Heneka, Michael T., Teipel, Stefan J., Dyrba, Martin, Ballarini, Tommaso, Brosseron, Frederic, Bruno, Davide, Buerger, Katharina, Cosma, Nicoleta-Carmen, Dechent, Peter, Dobisch, Laura, Duezel, Emrah, Ewers, Michael, Fliessbach, Klaus, Haynes, John D., Janowitz, Daniel, Kilimann, Ingo, Laske, Christoph, Maier, Franziska, Metzger, Coraline D., Munk, Matthias H., Peters, Oliver, Pomara, Nunzio, Preis, Lukas, Priller, Josef, Ramirez, Alfredo, Roy, Nina, Scheffler, Klaus, Schneider, Anja, Schott, Bjoern H., Spottke, Annika, Spruth, Eike J., Wagner, Michael, Wiltfang, Jens, Jessen, Frank, and Heneka, Michael T.
Abstract: Background: Inflammation has been described as a key pathogenic event in Alzheimer's disease (AD), downstream of amyloid and tau pathology. Preclinical and clinical data suggest that the cholinergic basal forebrain may moderate inflammatory response to different pathologies. Objective: To study the association of cholinergic basal forebrain volume and functional connectivity with measures of neuroinflammation in people from the AD spectrum. Methods: We studied 261 cases from the DELCODEcohort, including people with subjective cognitive decline, mild cognitive impairment, AD dementia, first degree relatives, and healthy controls. Using Bayesian ANCOVA, we tested associations of MRI indices of cholinergic basal forebrain volume and functional connectivity with cerebrospinal fluid (CSF) levels of sTREM2 as a marker of microglia activation, and serum levels of complement C3. Using Bayesian elastic net regression, we determined associations between basal forebrain measures and a large inflammation marker panel from CSF and serum. Results: We found anecdotal to moderate evidence in favor of the absence of an effect of basal forebrain volume and functional connectivity on CSF sTREM2 and serum C3 levels both in A beta(42)/ptau-positive and negative cases. Bayesian elastic net regression identified several CSF and serum markers of inflammation that were associated with basal forebrain volume and functional connectivity. The effect sizes were moderate to small. Conclusion: Our data-driven analyses generate the hypothesis that cholinergic basal forebrain may be involved in the neuroinflammation response to A beta(42) and phospho-tau pathology in people from the AD spectrum. This hypothesis needs to be tested in independent samples.
Published: 2022

37. Lifelong experiences as a proxy of cognitive reserve moderate the association between connectivity and cognition in Alzheimer's disease

Author: Ersoezlue, Ersin, Rauchmann, Boris-Stephan, Schneider-Axmann, Thomas, Wagner, Michael, Ballarini, Tommaso, Tato, Maia, Utecht, Julia, Kurz, Carolin, Papazov, Boris, Guersel, Selim, Burow, Lena, Koller, Gabriele, Stoecklein, Sophia, Keeser, Daniel, Bartels, Claudia, Brosseron, Frederic, Buerger, Katharina, Cetindag, Arda C., Dechent, Peter, Dobisch, Laura, Ewers, Michael, Fliessbach, Klaus, Frommann, Ingo, Haynes, John D., Heneka, Michael T., Janowitz, Daniel, Kilimann, Ingo, Kleinedam, Luca, Laske, Christoph, Maier, Franziska, Metzger, Coraline D., Munk, Matthias H., Peters, Oliver, Preis, Lukas, Priller, Josef, Ramirez, Alfredo, Roeske, Sandra, Roy, Nina, Scheffler, Klaus, Schneider, Anja, Spottke, Annika, Spruth, Eike J., Teipel, Stefan, Wiltfang, Jens, Wolfsgruber, Steffen, Yakupov, Renat, Duezel, Emrah, Jessen, Frank, Perneczky, Robert, Ersoezlue, Ersin, Rauchmann, Boris-Stephan, Schneider-Axmann, Thomas, Wagner, Michael, Ballarini, Tommaso, Tato, Maia, Utecht, Julia, Kurz, Carolin, Papazov, Boris, Guersel, Selim, Burow, Lena, Koller, Gabriele, Stoecklein, Sophia, Keeser, Daniel, Bartels, Claudia, Brosseron, Frederic, Buerger, Katharina, Cetindag, Arda C., Dechent, Peter, Dobisch, Laura, Ewers, Michael, Fliessbach, Klaus, Frommann, Ingo, Haynes, John D., Heneka, Michael T., Janowitz, Daniel, Kilimann, Ingo, Kleinedam, Luca, Laske, Christoph, Maier, Franziska, Metzger, Coraline D., Munk, Matthias H., Peters, Oliver, Preis, Lukas, Priller, Josef, Ramirez, Alfredo, Roeske, Sandra, Roy, Nina, Scheffler, Klaus, Schneider, Anja, Spottke, Annika, Spruth, Eike J., Teipel, Stefan, Wiltfang, Jens, Wolfsgruber, Steffen, Yakupov, Renat, Duezel, Emrah, Jessen, Frank, and Perneczky, Robert
Abstract: Alzheimer's disease (AD) is associated with alterations in functional connectivity (FC) of the brain. The FC underpinnings of CR, that is, lifelong experiences, are largely unknown. Resting-state FC and structural MRI were performed in 76 CSF amyloid-beta (A beta) negative healthy controls and 152 A beta positive individ-uals as an AD spectrum cohort (ADS; 55 with subjective cognitive decline, SCD; 52 with mild cognitive impairment; 45 with AD dementia). Following a region-of-interest (ROI) FC analysis, intrinsic network connectivity within the default-mode network (INC-DMN) and anti-correlation in INC between the DMN and dorsal attention network (DMN:DAN) were obtained as composite scores. CR was estimated by ed-ucation and Lifetime Experiences Questionnaire (LEQ). The association between INC-DMN and MEM was attenuated by higher LEQ scores in the entire ADS group, particularly in SCD. In ROI analyses, higher LEQ scores were associated with higher FC within the DMN in ADS group. INC-DMN remains relatively in-tact despite memory decline in individuals with higher lifetime activity estimates, supporting a role for functional networks in maintaining cognitive function in AD.(c) 2022 Elsevier Inc. All rights reserved.
Published: 2022

38. Musical Activity During Life Is Associated With Multi-Domain Cognitive and Brain Benefits in Older Adults

Author: Boettcher, Adriana, Zarucha, Alexis, Koebe, Theresa, Gaubert, Malo, Hoeppner, Angela, Altenstein, Slawek, Bartels, Claudia, Buerger, Katharina, Dechent, Peter, Dobisch, Laura, Ewers, Michael, Fliessbach, Klaus, Freiesleben, Silka Dawn, Frommann, Ingo, Haynes, John Dylan, Janowitz, Daniel, Kilimann, Ingo, Kleineidam, Luca, Laske, Christoph, Maier, Franziska, Metzger, Coraline, Munk, Matthias H. J., Perneczky, Robert, Peters, Oliver, Priller, Josef, Rauchmann, Boris-Stephan, Roy, Nina, Scheffler, Klaus, Schneider, Anja, Spottke, Annika, Teipel, Stefan J., Wiltfang, Jens, Wolfsgruber, Steffen, Yakupov, Renat, Duezel, Emrah, Jessen, Frank, Roeske, Sandra, Wagner, Michael, Kempermann, Gerd, Wirth, Miranka, Boettcher, Adriana, Zarucha, Alexis, Koebe, Theresa, Gaubert, Malo, Hoeppner, Angela, Altenstein, Slawek, Bartels, Claudia, Buerger, Katharina, Dechent, Peter, Dobisch, Laura, Ewers, Michael, Fliessbach, Klaus, Freiesleben, Silka Dawn, Frommann, Ingo, Haynes, John Dylan, Janowitz, Daniel, Kilimann, Ingo, Kleineidam, Luca, Laske, Christoph, Maier, Franziska, Metzger, Coraline, Munk, Matthias H. J., Perneczky, Robert, Peters, Oliver, Priller, Josef, Rauchmann, Boris-Stephan, Roy, Nina, Scheffler, Klaus, Schneider, Anja, Spottke, Annika, Teipel, Stefan J., Wiltfang, Jens, Wolfsgruber, Steffen, Yakupov, Renat, Duezel, Emrah, Jessen, Frank, Roeske, Sandra, Wagner, Michael, Kempermann, Gerd, and Wirth, Miranka
Abstract: Regular musical activity as a complex multimodal lifestyle activity is proposed to be protective against age-related cognitive decline and Alzheimer's disease. This cross-sectional study investigated the association and interplay between musical instrument playing during life, multi-domain cognitive abilities and brain morphology in older adults (OA) from the DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE) study. Participants reporting having played a musical instrument across three life periods (n = 70) were compared to controls without a history of musical instrument playing (n = 70), well-matched for reserve proxies of education, intelligence, socioeconomic status and physical activity. Participants with musical activity outperformed controls in global cognition, working memory, executive functions, language, and visuospatial abilities, with no effects seen for learning and memory. The musically active group had greater gray matter volume in the somatosensory area, but did not differ from controls in higher-order frontal, temporal, or hippocampal volumes. However, the association between gray matter volume in distributed frontal-to-temporal regions and cognitive abilities was enhanced in participants with musical activity compared to controls. We show that playing a musical instrument during life relates to better late-life cognitive abilities and greater brain capacities in OA. Musical activity may serve as a multimodal enrichment strategy that could help preserve cognitive and brain health in late life. Longitudinal and interventional studies are needed to support this notion.
Published: 2022

39. Amyloid pathology but not APOE epsilon 4 status is permissive for tau-related hippocampal dysfunction

Author: Duezel, Emrah, Ziegler, Gabriel, Berron, David, Maass, Anne, Schuetze, Hartmut, Cardenas-Blanco, Arturo, Glanz, Wenzel, Metzger, Coraline, Dobisch, Laura, Reuter, Martin, Spottke, Annika, Brosseron, Frederic, Fliessbach, Klaus, Heneka, Michael T., Laske, Christoph, Peters, Oliver, Priller, Josef, Spruth, Eike Jakob, Ramirez, Alfredo, Speck, Oliver, Schneider, Anja, Teipel, Stefan, Kilimann, Ingo, Jens, Wiltfang, Schott, Bjoern-Hendrik, Preis, Lukas, Gref, Daria, Maier, Franziska, Munk, Matthias H., Roy, Nina, Ballarini, Tomasso, Yakupov, Renat, Haynes, John Dylan, Dechent, Peter, Scheffler, Klaus, Wagner, Michael, Jessen, Frank, Duezel, Emrah, Ziegler, Gabriel, Berron, David, Maass, Anne, Schuetze, Hartmut, Cardenas-Blanco, Arturo, Glanz, Wenzel, Metzger, Coraline, Dobisch, Laura, Reuter, Martin, Spottke, Annika, Brosseron, Frederic, Fliessbach, Klaus, Heneka, Michael T., Laske, Christoph, Peters, Oliver, Priller, Josef, Spruth, Eike Jakob, Ramirez, Alfredo, Speck, Oliver, Schneider, Anja, Teipel, Stefan, Kilimann, Ingo, Jens, Wiltfang, Schott, Bjoern-Hendrik, Preis, Lukas, Gref, Daria, Maier, Franziska, Munk, Matthias H., Roy, Nina, Ballarini, Tomasso, Yakupov, Renat, Haynes, John Dylan, Dechent, Peter, Scheffler, Klaus, Wagner, Michael, and Jessen, Frank
Abstract: We investigated whether the impact of tau-pathology on memory performance and on hippocampal/medial temporal memory function in non-demented individuals depends on the presence of amyloid pathology, irrespective of diagnostic clinical stage. We conducted a cross-sectional analysis of the observational, multicentric DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE). Two hundred and thirty-five participants completed task functional MRI and provided CSF (92 cognitively unimpaired, 100 experiencing subjective cognitive decline and 43 with mild cognitive impairment). Presence (A+) and absence (A-) of amyloid pathology was defined by CSF amyloid-beta(42) (A beta 42) levels. Free recall performance in the Free and Cued Selective Reminding Test, scene recognition memory accuracy and hippocampal/medial temporal functional MRI novelty responses to scene images were related to CSF total-tau and phospho-tau levels separately for A+ and A- individuals. We found that total-tau and phospho-tau levels were negatively associated with memory performance in both tasks and with novelty responses in the hippocampus and amygdala, in interaction with A beta 42 levels. Subgroup analyses showed that these relationships were only present in A+ and remained stable when very high levels of tau (>700 pg/ml) and phospho-tau (>100 pg/ml) were excluded. These relationships were significant with diagnosis, age, education, sex, assessment site and A beta 42 levels as covariates. They also remained significant after propensity score based matching of phospho-tau levels across A+ and A- groups. After classifying this matched sample for phospho-tau pathology (T-/T+), individuals with A+/T+ were significantly more memory-impaired than A-/T+ despite the fact that both groups had the same amount of phospho-tau pathology. ApoE status (presence of the E4 allele), a known genetic risk factor for Alzheimer's disease, did not mediate the relationship between tau pathology and hippocampal fun
Published: 2022

40. 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

41. Subjective cognitive decline and stage 2 of Alzheimer disease in patients from memory centers.

Author: Jessen, Frank, Wolfsgruber, Steffen, Kleineindam, Luca, Spottke, Annika, Altenstein, Slawek, Bartels, Claudia, Berger, Moritz, Brosseron, Frederic, Daamen, Marcel, Dichgans, Martin, Dobisch, Laura, Ewers, Michael, Fenski, Friederike, Fliessbach, Klaus, Freiesleben, Silka D., Glanz, Wenzel, Görß, Doreen, Gürsel, Selim, Janowitz, Daniel, and Kilimann, Ingo
Abstract: Introduction: It is uncertain whether subjective cognitive decline (SCD) in individuals who seek medical help serves the identification of the initial symptomatic stage 2 of the Alzheimer's disease (AD) continuum. Methods: Cross‐sectional and longitudinal data from the multicenter, memory clinic–based DELCODE study. Results: The SCD group showed slightly worse cognition as well as more subtle functional and behavioral symptoms than the control group (CO). SCD–A+ cases (39.3% of all SCD) showed greater hippocampal atrophy, lower cognitive and functional performance, and more behavioral symptoms than CO–A+. Amyloid concentration in the CSF had a greater effect on longitudinal cognitive decline in SCD than in the CO group. Discussion: Our data suggests that SCD serves the identification of stage 2 of the AD continuum and that stage 2, operationalized as SCD‐A+, is associated with subtle, but extended impact of AD pathology in terms of neurodegeneration, symptoms and clinical progression. [ABSTRACT FROM AUTHOR]
Published: 2023
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42. Subjective cognitive decline and stage 2 of Alzheimer disease in patients from memory centers

Author: Jessen, Frank, primary, Wolfsgruber, Steffen, additional, Kleineindam, Luca, additional, Spottke, Annika, additional, Altenstein, Slawek, additional, Bartels, Claudia, additional, Berger, Moritz, additional, Brosseron, Frederic, additional, Daamen, Marcel, additional, Dichgans, Martin, additional, Dobisch, Laura, additional, Ewers, Michael, additional, Fenski, Friederike, additional, Fliessbach, Klaus, additional, Freiesleben, Silka D., additional, Glanz, Wenzel, additional, Görß, Doreen, additional, Gürsel, Selim, additional, Janowitz, Daniel, additional, Kilimann, Ingo, additional, Kobeleva, Xenia, additional, Lohse, Andrea, additional, Maier, Franziska, additional, Metzger, Coraline, additional, Munk, Matthias, additional, Preis, Lukas, additional, Sanzenbacher, Carolin, additional, Spruth, Eike, additional, Rauchmann, Boris, additional, Vukovich, Ruth, additional, Yakupov, Renat, additional, Weyrauch, Anne‐Sophie, additional, Ziegler, Gabriel, additional, Schmid, Matthias, additional, Laske, Christoph, additional, Perneczky, Robert, additional, Schneider, Anja, additional, Wiltfang, Jens, additional, Teipel, Stefan, additional, Bürger, Katharina, additional, Priller, Josef, additional, Peters, Oliver, additional, Ramirez, Alfredo, additional, Boecker, Henning, additional, Heneka, Michael T., additional, Wagner, Michael, additional, and Düzel, Emrah, additional
Published: 2022
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43. Amyloid pathology but notAPOEε4 status is permissive for tau-related hippocampal dysfunction

Author: Düzel, Emrah, primary, Ziegler, Gabriel, additional, Berron, David, additional, Maass, Anne, additional, Schütze, Hartmut, additional, Cardenas-Blanco, Arturo, additional, Glanz, Wenzel, additional, Metzger, Coraline, additional, Dobisch, Laura, additional, Reuter, Martin, additional, Spottke, Annika, additional, Brosseron, Frederic, additional, Fliessbach, Klaus, additional, Heneka, Michael T, additional, Laske, Christoph, additional, Peters, Oliver, additional, Priller, Josef, additional, Spruth, Eike Jakob, additional, Ramirez, Alfredo, additional, Speck, Oliver, additional, Schneider, Anja, additional, Teipel, Stefan, additional, Kilimann, Ingo, additional, Jens, Wiltfang, additional, Schott, Björn-Hendrik, additional, Preis, Lukas, additional, Gref, Daria, additional, Maier, Franziska, additional, Munk, Matthias H, additional, Roy, Nina, additional, Ballarini, Tomasso, additional, Yakupov, Renat, additional, Haynes, John Dylan, additional, Dechent, Peter, additional, Scheffler, Klaus, additional, Wagner, Michael, additional, and Jessen, Frank, additional
Published: 2022
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44. 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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45. Soluble TAM receptors sAXL and sTyro3 predict structural and functional protection in Alzheimer’s disease

Author: Brosseron, Frederic, primary, Maass, Anne, additional, Kleineidam, Luca, additional, Ravichandran, Kishore Aravind, additional, González, Pablo García, additional, McManus, Róisín M., additional, Ising, Christina, additional, Santarelli, Francesco, additional, Kolbe, Carl-Christian, additional, Häsler, Lisa M., additional, Wolfsgruber, Steffen, additional, Marquié, Marta, additional, Boada, Mercè, additional, Orellana, Adelina, additional, de Rojas, Itziar, additional, Röske, Sandra, additional, Peters, Oliver, additional, Cosma, Nicoleta-Carmen, additional, Cetindag, Arda, additional, Wang, Xiao, additional, Priller, Josef, additional, Spruth, Eike J., additional, Altenstein, Slawek, additional, Schneider, Anja, additional, Fliessbach, Klaus, additional, Wiltfang, Jens, additional, Schott, Björn H., additional, Bürger, Katharina, additional, Janowitz, Daniel, additional, Dichgans, Martin, additional, Perneczky, Robert, additional, Rauchmann, Boris-Stephan, additional, Teipel, Stefan, additional, Kilimann, Ingo, additional, Goerss, Doreen, additional, Laske, Christoph, additional, Munk, Matthias H., additional, Düzel, Emrah, additional, Yakupov, Renat, additional, Dobisch, Laura, additional, Metzger, Coraline D., additional, Glanz, Wenzel, additional, Ewers, Michael, additional, Dechent, Peter, additional, Haynes, John Dylan, additional, Scheffler, Klaus, additional, Roy, Nina, additional, Rostamzadeh, Ayda, additional, Teunissen, Charlotte E., additional, Marchant, Natalie L., additional, Spottke, Annika, additional, Jucker, Mathias, additional, Latz, Eicke, additional, Wagner, Michael, additional, Mengel, David, additional, Synofzik, Matthis, additional, Jessen, Frank, additional, Ramirez, Alfredo, additional, Ruiz, Agustín, additional, and Heneka, Michael T., additional
Published: 2022
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46. Association of Cholinergic Basal Forebrain Volume and Functional Connectivity with Markers of Inflammatory Response in the Alzheimer’s Disease Spectrum

Author: Teipel, Stefan J., primary, Dyrba, Martin, additional, Ballarini, Tommaso, additional, Brosseron, Frederic, additional, Bruno, Davide, additional, Buerger, Katharina, additional, Cosma, Nicoleta-Carmen, additional, Dechent, Peter, additional, Dobisch, Laura, additional, Düzel, Emrah, additional, Ewers, Michael, additional, Fliessbach, Klaus, additional, Haynes, John D., additional, Janowitz, Daniel, additional, Kilimann, Ingo, additional, Laske, Christoph, additional, Maier, Franziska, additional, Metzger, Coraline D., additional, Munk, Matthias H., additional, Peters, Oliver, additional, Pomara, Nunzio, additional, Preis, Lukas, additional, Priller, Josef, additional, Ramírez, Alfredo, additional, Roy, Nina, additional, Scheffler, Klaus, additional, Schneider, Anja, additional, Schott, Björn H., additional, Spottke, Annika, additional, Spruth, Eike J., additional, Wagner, Michael, additional, Wiltfang, Jens, additional, Jessen, Frank, additional, and Heneka, Michael T., additional
Published: 2022
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47. Additional file 5 of Improving 3D convolutional neural network comprehensibility via interactive visualization of relevance maps: evaluation in Alzheimer’s disease

Author: Dyrba, Martin, Hanzig, Moritz, Altenstein, Slawek, Bader, Sebastian, Ballarini, Tommaso, Brosseron, Frederic, Buerger, Katharina, Cantré, Daniel, Dechent, Peter, Dobisch, Laura, Düzel, Emrah, Ewers, Michael, Fliessbach, Klaus, Glanz, Wenzel, Haynes, John-Dylan, Heneka, Michael T., Janowitz, Daniel, Keles, Deniz B., Kilimann, Ingo, Laske, Christoph, Maier, Franziska, Metzger, Coraline D., Munk, Matthias H., Perneczky, Robert, Peters, Oliver, Preis, Lukas, Priller, Josef, Rauchmann, Boris, Roy, Nina, Scheffler, Klaus, Schneider, Anja, Schott, Björn H., Spottke, Annika, Spruth, Eike J., Weber, Marc-André, Ertl-Wagner, Birgit, Wagner, Michael, Wiltfang, Jens, Jessen, Frank, and Teipel, Stefan J.
Abstract: Additional file 5: Supplementary Figure 3. Comparison of mean relevance maps between samples.
Published: 2021
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48. Additional file 2 of Improving 3D convolutional neural network comprehensibility via interactive visualization of relevance maps: evaluation in Alzheimer’s disease

Author: Dyrba, Martin, Hanzig, Moritz, Altenstein, Slawek, Bader, Sebastian, Ballarini, Tommaso, Brosseron, Frederic, Buerger, Katharina, Cantré, Daniel, Dechent, Peter, Dobisch, Laura, Düzel, Emrah, Ewers, Michael, Fliessbach, Klaus, Glanz, Wenzel, Haynes, John-Dylan, Heneka, Michael T., Janowitz, Daniel, Keles, Deniz B., Kilimann, Ingo, Laske, Christoph, Maier, Franziska, Metzger, Coraline D., Munk, Matthias H., Perneczky, Robert, Peters, Oliver, Preis, Lukas, Priller, Josef, Rauchmann, Boris, Roy, Nina, Scheffler, Klaus, Schneider, Anja, Schott, Björn H., Spottke, Annika, Spruth, Eike J., Weber, Marc-André, Ertl-Wagner, Birgit, Wagner, Michael, Wiltfang, Jens, Jessen, Frank, and Teipel, Stefan J.
Abstract: Additional file 2: Supplementary Table 2. Group separation performance for hippocampus volume and the convolutional neural network models for raw input data.
Published: 2021
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49. Additional file 6 of Improving 3D convolutional neural network comprehensibility via interactive visualization of relevance maps: evaluation in Alzheimer’s disease

Author: Dyrba, Martin, Hanzig, Moritz, Altenstein, Slawek, Bader, Sebastian, Ballarini, Tommaso, Brosseron, Frederic, Buerger, Katharina, Cantré, Daniel, Dechent, Peter, Dobisch, Laura, Düzel, Emrah, Ewers, Michael, Fliessbach, Klaus, Glanz, Wenzel, Haynes, John-Dylan, Heneka, Michael T., Janowitz, Daniel, Keles, Deniz B., Kilimann, Ingo, Laske, Christoph, Maier, Franziska, Metzger, Coraline D., Munk, Matthias H., Perneczky, Robert, Peters, Oliver, Preis, Lukas, Priller, Josef, Rauchmann, Boris, Roy, Nina, Scheffler, Klaus, Schneider, Anja, Schott, Björn H., Spottke, Annika, Spruth, Eike J., Weber, Marc-André, Ertl-Wagner, Birgit, Wagner, Michael, Wiltfang, Jens, Jessen, Frank, and Teipel, Stefan J.
Subjects: nervous system
Abstract: Additional file 6: Supplementary Figure 4. Correlation matrix of hippocampus volume (residualized) and several brain regions’ relevance scores for DELCODE participants and the model trained on the whole ADNI-GO/2 dataset.
Published: 2021
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50. Additional file 3 of Improving 3D convolutional neural network comprehensibility via interactive visualization of relevance maps: evaluation in Alzheimer’s disease

Author: Dyrba, Martin, Hanzig, Moritz, Altenstein, Slawek, Bader, Sebastian, Ballarini, Tommaso, Brosseron, Frederic, Buerger, Katharina, Cantré, Daniel, Dechent, Peter, Dobisch, Laura, Düzel, Emrah, Ewers, Michael, Fliessbach, Klaus, Glanz, Wenzel, Haynes, John-Dylan, Heneka, Michael T., Janowitz, Daniel, Keles, Deniz B., Kilimann, Ingo, Laske, Christoph, Maier, Franziska, Metzger, Coraline D., Munk, Matthias H., Perneczky, Robert, Peters, Oliver, Preis, Lukas, Priller, Josef, Rauchmann, Boris, Roy, Nina, Scheffler, Klaus, Schneider, Anja, Schott, Björn H., Spottke, Annika, Spruth, Eike J., Weber, Marc-André, Ertl-Wagner, Birgit, Wagner, Michael, Wiltfang, Jens, Jessen, Frank, and Teipel, Stefan J.
Abstract: Additional file 3: Supplementary Figure 1. UML diagram of the interactive visualization application.
Published: 2021
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