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1. Neuroinflammation in Alzheimer disease

Author

Heneka, Michael T., van der Flier, Wiesje M., Jessen, Frank, Hoozemanns, Jeroen, Thal, Dietmar Rudolf, Boche, Delphine, Brosseron, Frederic, Teunissen, Charlotte, Zetterberg, Henrik, Jacobs, Andreas H., Edison, Paul, Ramirez, Alfredo, Cruchaga, Carlos, Lambert, Jean-Charles, Laza, Agustin Ruiz, Sanchez-Mut, Jose Vicente, Fischer, Andre, Castro-Gomez, Sergio, Stein, Thor D., Kleineidam, Luca, Wagner, Michael, Neher, Jonas J., Cunningham, Colm, Singhrao, Sim K., Prinz, Marco, Glass, Christopher K., Schlachetzki, Johannes C. M., Butovsky, Oleg, Kleemann, Kilian, De Jaeger, Philip L., Scheiblich, Hannah, Brown, Guy C., Landreth, Gary, Moutinho, Miguel, Grutzendler, Jaime, Gomez-Nicola, Diego, McManus, Róisín M., Andreasson, Katrin, Ising, Christina, Karabag, Deniz, Baker, Darren J., Liddelow, Shane A., Verkhratsky, Alexei, Tansey, Malu, Monsonego, Alon, Aigner, Ludwig, Dorothée, Guillaume, Nave, Klaus-Armin, Simons, Mikael, Constantin, Gabriela, Rosenzweig, Neta, Pascual, Alberto, Petzold, Gabor C., Kipnis, Jonathan, Venegas, Carmen, Colonna, Marco, Walter, Jochen, Tenner, Andrea J., O’Banion, M. Kerry, Steinert, Joern R., Feinstein, Douglas L., Sastre, Magdalena, Bhaskar, Kiran, Hong, Soyon, Schafer, Dorothy P., Golde, Todd, Ransohoff, Richard M., Morgan, David, Breitner, John, Mancuso, Renzo, and Riechers, Sean-Patrick

Published
2024
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2. Blood-based quantification of Aβ oligomers indicates impaired clearance from brain in ApoE ε4 positive subjects

Author

Blömeke, Lara, Rehn, Fabian, Pils, Marlene, Kraemer-Schulien, Victoria, Cousin, Anneliese, Kutzsche, Janine, Bujnicki, Tuyen, Freiesleben, Silka D., Schneider, Luisa-Sophie, Preis, Lukas, Priller, Josef, Spruth, Eike J., Altenstein, Slawek, Schneider, Anja, Fliessbach, Klaus, Wiltfang, Jens, Hansen, Niels, Rostamzadeh, Ayda, Düzel, Emrah, Glanz, Wenzel, Incesoy, Enise I., Buerger, Katharina, Janowitz, Daniel, Ewers, Michael, Perneczky, Robert, Rauchmann, Boris-Stephan, Teipel, Stefan, Kilimann, Ingo, Laske, Christoph, Munk, Matthias H., Spottke, Annika, Roy, Nina, Heneka, Michael T., Brosseron, Frederic, Wagner, Michael, Roeske, Sandra, Ramirez, Alfredo, Schmid, Matthias, Jessen, Frank, Bannach, Oliver, Peters, Oliver, and Willbold, Dieter

Published
2024
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3. Cognitive reserve against Alzheimer’s pathology is linked to brain activity during memory formation

Author

Vockert, Niklas, Machts, Judith, Kleineidam, Luca, Nemali, Aditya, Incesoy, Enise I., Bernal, Jose, Schütze, Hartmut, Yakupov, Renat, Peters, Oliver, Gref, Daria, Schneider, Luisa Sophie, Preis, Lukas, Priller, Josef, Spruth, Eike Jakob, Altenstein, Slawek, Schneider, Anja, Fliessbach, Klaus, Wiltfang, Jens, Rostamzadeh, Ayda, Glanz, Wenzel, Teipel, Stefan, Kilimann, Ingo, Goerss, Doreen, Laske, Christoph, Munk, Matthias H., Spottke, Annika, Roy, Nina, Heneka, Michael T., Brosseron, Frederic, Wagner, Michael, Wolfsgruber, Steffen, Dobisch, Laura, Dechent, Peter, Hetzer, Stefan, Scheffler, Klaus, Zeidman, Peter, Stern, Yaakov, Schott, Björn H., Jessen, Frank, Düzel, Emrah, Maass, Anne, and Ziegler, Gabriel

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

Author

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

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

Author

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

Published
2024
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7. 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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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. 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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10. 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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11. 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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12. 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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13. Single-value brain activity scores reflect both severity and risk across the Alzheimer's continuum.

Author

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

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

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

Published
2024
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14. 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, and Heneka, Michael T.

Published
2022
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15. Left frontal hub connectivity delays cognitive impairment in autosomal-dominant and sporadic Alzheimer’s disease

Author

Franzmeier, Nicolai, Düzel, Emrah, Jessen, Frank, Buerger, Katharina, Levin, Johannes, Duering, Marco, Dichgans, Martin, Haass, Christian, Suárez-Calvet, Marc, Fagan, Anne M, Paumier, Katrina, Benzinger, Tammie, Masters, Colin L, Morris, John C, Perneczky, Robert, Janowitz, Daniel, Catak, Cihan, Wolfsgruber, Steffen, Wagner, Michael, Teipel, Stefan, Kilimann, Ingo, Ramirez, Alfredo, Rossor, Martin, Jucker, Mathias, Chhatwal, Jasmeer, Spottke, Annika, Boecker, Henning, Brosseron, Frederic, Falkai, Peter, Fliessbach, Klaus, Heneka, Michael T, Laske, Christoph, Nestor, Peter, Peters, Oliver, Fuentes, Manuel, Menne, Felix, Priller, Josef, Spruth, Eike J, Franke, Christiana, Schneider, Anja, Kofler, Barbara, Westerteicher, Christine, Speck, Oliver, Wiltfang, Jens, Bartels, Claudia, Caballero, Miguel Ángel Araque, Metzger, Coraline, Bittner, Daniel, Weiner, Michael, Lee, Jae-Hong, Salloway, Stephen, Danek, Adrian, Goate, Alison, Schofield, Peter R, Bateman, Randall J, and Ewers, Michael

Subjects
Clinical Trials and Supportive Activities, Brain Disorders, Aging, Basic Behavioral and Social Science, Dementia, Neurosciences, Behavioral and Social Science, Acquired Cognitive Impairment, Clinical Research, Alzheimer's Disease, Neurodegenerative, Biomedical Imaging, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Aetiology, 2.1 Biological and endogenous factors, Neurological, Adult, Alzheimer Disease, Amyloid beta-Protein Precursor, Brain Mapping, Cognitive Dysfunction, Female, Frontal Lobe, Functional Laterality, Humans, Imaging, Three-Dimensional, Magnetic Resonance Imaging, Male, Middle Aged, Mutation, Nerve Net, Presenilin-1, Presenilin-2, Alzheimer's disease, cognitive reserve, resting state connectivity, memory, dementia biomarkers, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery
Abstract

Patients with Alzheimer's disease vary in their ability to sustain cognitive abilities in the presence of brain pathology. A major open question is which brain mechanisms may support higher reserve capacity, i.e. relatively high cognitive performance at a given level of Alzheimer's pathology. Higher functional MRI-assessed functional connectivity of a hub in the left frontal cortex is a core candidate brain mechanism underlying reserve as it is associated with education (i.e. a protective factor often associated with higher reserve) and attenuated cognitive impairment in prodromal Alzheimer's disease. However, no study has yet assessed whether such hub connectivity of the left frontal cortex supports reserve throughout the evolution of pathological brain changes in Alzheimer's disease, including the presymptomatic stage when cognitive decline is subtle. To address this research gap, we obtained cross-sectional resting state functional MRI in 74 participants with autosomal dominant Alzheimer's disease, 55 controls from the Dominantly Inherited Alzheimer's Network and 75 amyloid-positive elderly participants, as well as 41 amyloid-negative cognitively normal elderly subjects from the German Center of Neurodegenerative Diseases multicentre study on biomarkers in sporadic Alzheimer's disease. For each participant, global left frontal cortex connectivity was computed as the average resting state functional connectivity between the left frontal cortex (seed) and each voxel in the grey matter. As a marker of disease stage, we applied estimated years from symptom onset in autosomal dominantly inherited Alzheimer's disease and cerebrospinal fluid tau levels in sporadic Alzheimer's disease cases. In both autosomal dominant and sporadic Alzheimer's disease patients, higher levels of left frontal cortex connectivity were correlated with greater education. For autosomal dominant Alzheimer's disease, a significant left frontal cortex connectivity × estimated years of onset interaction was found, indicating slower decline of memory and global cognition at higher levels of connectivity. Similarly, in sporadic amyloid-positive elderly subjects, the effect of tau on cognition was attenuated at higher levels of left frontal cortex connectivity. Polynomial regression analysis showed that the trajectory of cognitive decline was shifted towards a later stage of Alzheimer's disease in patients with higher levels of left frontal cortex connectivity. Together, our findings suggest that higher resilience against the development of cognitive impairment throughout the early stages of Alzheimer's disease is at least partially attributable to higher left frontal cortex-hub connectivity.

Published
2018

16. 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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17. 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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18. Aβ oligomers peak in early stages of Alzheimer's disease preceding tau pathology

Author

Blömeke, Lara, primary, Rehn, Fabian, additional, Kraemer‐Schulien, Victoria, additional, Kutzsche, Janine, additional, Pils, Marlene, additional, Bujnicki, Tuyen, additional, Lewczuk, Piotr, additional, Kornhuber, Johannes, additional, Freiesleben, Silka D., additional, Schneider, Luisa‐Sophie, additional, Preis, Lukas, additional, Priller, Josef, additional, Spruth, Eike J., additional, Altenstein, Slawek, additional, Lohse, Andrea, additional, Schneider, Anja, additional, Fliessbach, Klaus, additional, Wiltfang, Jens, additional, Hansen, Niels, 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, Sanzenbacher, Carolin, additional, Spottke, Annika, additional, Roy‐Kluth, Nina, additional, Heneka, Michael T., additional, Brosseron, Frederic, additional, Wagner, Michael, additional, Wolfsgruber, Steffen, additional, Kleineidam, Luca, additional, Stark, Melina, additional, Schmid, Matthias, additional, Jessen, Frank, additional, Bannach, Oliver, additional, Willbold, Dieter, additional, and Peters, Oliver, additional

Published
2024
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19. The BDNFVal66Met SNP modulates the association between beta-amyloid and hippocampal disconnection in Alzheimer’s disease

Author

Franzmeier, Nicolai, Ren, Jinyi, Damm, Alexander, Monté-Rubio, Gemma, Boada, Mercè, Ruiz, Agustín, Ramirez, Alfredo, Jessen, Frank, Düzel, Emrah, Rodríguez Gómez, Octavio, Benzinger, Tammie, Goate, Alison, Karch, Celeste M., Fagan, Anne M., McDade, Eric, Buerger, Katharina, Levin, Johannes, Duering, Marco, Dichgans, Martin, Suárez-Calvet, Marc, Haass, Christian, Gordon, Brian A., Lim, Yen Ying, Masters, Colin L., Janowitz, Daniel, Catak, Cihan, Wolfsgruber, Steffen, Wagner, Michael, Milz, Esther, Moreno-Grau, Sonia, Teipel, Stefan, Grothe, Michel J, Kilimann, Ingo, Rossor, Martin, Fox, Nick, Laske, Christoph, Chhatwal, Jasmeer, Falkai, Peter, Perneczky, Robert, Lee, Jae-Hong, Spottke, Annika, Boecker, Henning, Brosseron, Frederic, Fliessbach, Klaus, Heneka, Michael T., Nestor, Peter, Peters, Oliver, Fuentes, Manuel, Menne, Felix, Priller, Josef, Spruth, Eike J., Franke, Christiana, Schneider, Anja, Westerteicher, Christine, Speck, Oliver, Wiltfang, Jens, Bartels, Claudia, Araque Caballero, Miguel Ángel, Metzger, Coraline, Bittner, Daniel, Salloway, Stephen, Danek, Adrian, Hassenstab, Jason, Yakushev, Igor, Schofield, Peter R., Morris, John C., Bateman, Randall J., and Ewers, Michael

Published
2021
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20. Multimodal MRI analysis of basal forebrain structure and function across the Alzheimer’s disease spectrum

Author

Herdick, Meret, Dyrba, Martin, Fritz, Hans-Christian J., Altenstein, Slawek, Ballarini, Tommaso, Brosseron, Frederic, Buerger, Katharina, Can Cetindag, Arda, Dechent, Peter, Dobisch, Laura, Duezel, Emrah, Ertl-Wagner, Birgit, Fliessbach, Klaus, Dawn Freiesleben, Silka, Frommann, Ingo, Glanz, Wenzel, Dylan Haynes, John, Heneka, Michael T., Janowitz, Daniel, Kilimann, Ingo, Laske, Christoph, Metzger, Coraline D., Munk, Matthias H., Peters, Oliver, Priller, Josef, Roy, Nina, Scheffler, Klaus, Schneider, Anja, Spottke, Annika, Jakob Spruth, Eike, Tscheuschler, Maike, Vukovich, Ruth, Wiltfang, Jens, Jessen, Frank, Teipel, Stefan, and Grothe, Michel J.

Published
2020
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21. Neuroinflammation in Alzheimer's disease

Author

Heneka, Michael T, Carson, Monica J, Khoury, Joseph El, Landreth, Gary E, Brosseron, Frederic, Feinstein, Douglas L, Jacobs, Andreas H, Wyss-Coray, Tony, Vitorica, Javier, Ransohoff, Richard M, Herrup, Karl, Frautschy, Sally A, Finsen, Bente, Brown, Guy C, Verkhratsky, Alexei, Yamanaka, Koji, Koistinaho, Jari, Latz, Eicke, Halle, Annett, Petzold, Gabor C, Town, Terrence, Morgan, Dave, Shinohara, Mari L, Perry, V Hugh, Holmes, Clive, Bazan, Nicolas G, Brooks, David J, Hunot, Stéphane, Joseph, Bertrand, Deigendesch, Nikolaus, Garaschuk, Olga, Boddeke, Erik, Dinarello, Charles A, Breitner, John C, Cole, Greg M, Golenbock, Douglas T, and Kummer, Markus P

Subjects
Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurosciences, Brain Disorders, Alzheimer's Disease, Acquired Cognitive Impairment, Prevention, Neurodegenerative, Dementia, Aging, Aetiology, 2.1 Biological and endogenous factors, Neurological, Inflammatory and immune system, Alzheimer Disease, Animals, Anti-Inflammatory Agents, Non-Steroidal, Astrocytes, Biomarkers, Brain Injuries, Clinical Trials as Topic, Disease Models, Animal, Disease Progression, Humans, Immunity, Innate, Immunization, Inflammation, Inflammation Mediators, Locus Coeruleus, Microglia, Nootropic Agents, Obesity, Phagocytosis, Protein Folding, Risk Factors, Severity of Illness Index, Clinical Sciences, Neurology & Neurosurgery
Abstract

Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment, but includes strong interactions with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on microglia and astroglia, and trigger an innate immune response characterised by release of inflammatory mediators, which contribute to disease progression and severity. Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded proteins and the inflammatory reaction. External factors, including systemic inflammation and obesity, are likely to interfere with immunological processes of the brain and further promote disease progression. Modulation of risk factors and targeting of these immune mechanisms could lead to future therapeutic or preventive strategies for Alzheimer's disease.

Published
2015

22. 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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23. A microRNA signature that correlates with cognition and is a target against cognitive decline

Author

Islam, Md Rezaul, Kaurani, Lalit, Berulava, Tea, Heilbronner, Urs, Budde, Monika, Centeno, Tonatiuh Pena, Elerdashvili, Vakthang, Zafieriou, Maria‐Patapia, Benito, Eva, Sertel, Sinem M, Goldberg, Maria, Senner, Fanny, Kalman, Janos L, Burkhardt, Susanne, Oepen, Anne Sophie, Sakib, Mohammad Sadman, Kerimoglu, Cemil, Wirths, Oliver, Bickeböller, Heike, Bartels, Claudia, Brosseron, Frederic, Buerger, Katharina, Cosma, Nicoleta‐Carmen, Fliessbach, Klaus, Heneka, Michael T., Janowitz, Daniel, Kilimann, Ingo, Kleinedam, Luca, Laske, Christoph, Metzger, Coraline D, Munk, Matthias H, Perneczky, Robert, Peters, Oliver, Priller, Josef, Rauchmann, Boris S., Roy, Nina, Schneider, Anja, Spottke, Annika, Spruth, Eike J, Teipel, Stefan, Tscheuschler, Maike, Wagner, Michael, Wiltfang, Jens, Düzel, Emrah, Jessen, Frank, Rizzoli, Silvio O, Zimmermann, Wolfram‐Hubertus, Schulze, Thomas G, Falkai, Peter, Sananbenesi, Farahnaz, and Fischer, Andre

Published
2021
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25. 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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26. Symptomatic Clusters Related to Amyloid Positivity in Cognitively Unimpaired Individuals.

Author

Sannemann, Lena, Bartels, Claudia, Brosseron, Frederic, Buerger, Katharina, Fliessbach, Klaus, Freiesleben, Silka Dawn, Frommann, Ingo, Glanz, Wenzel, Heneka, Michael T., Janowitz, Daniel, Kilimann, Ingo, Kleineidam, Luca, Lammerding, Dominik, Laske, Christoph, Munk, Matthias H.J., Perneczky, Robert, Peters, Oliver, Priller, Josef, Rauchmann, Boris-Stephan, and Rostamzadeh, Ayda

Subjects
AMYLOID, ALZHEIMER'S disease, COGNITIVE interviewing, CEREBROSPINAL fluid, COGNITION disorders
Abstract

Background: The NIA-AA Research Framework on Alzheimer's disease (AD) proposes a transitional stage (stage 2) characterized by subtle cognitive decline, subjective cognitive decline (SCD) and mild neurobehavioral symptoms (NPS). Objective: To identify participant clusters based on stage 2 features and assess their association with amyloid positivity in cognitively unimpaired individuals. Methods: We included baseline data of N = 338 cognitively unimpaired participants from the DELCODE cohort with data on cerebrospinal fluid biomarkers for AD. Classification into the AD continuum (i.e., amyloid positivity, A+) was based on Aβ42/40 status. Neuropsychological test data were used to assess subtle objective cognitive dysfunction (OBJ), the subjective cognitive decline interview (SCD-I) was used to detect SCD, and the Neuropsychiatric Inventory Questionnaire (NPI-Q) was used to assess NPS. A two-step cluster analysis was carried out and differences in AD biomarkers between clusters were analyzed. Results: We identified three distinct participant clusters based on presented symptoms. The highest rate of A+ participants (47.6%) was found in a cluster characterized by both OBJ and SCD. A cluster of participants that presented with SCD and NPS (A+:26.6%) and a cluster of participants with overall few symptoms (A+:19.7%) showed amyloid positivity in a range that was not higher than the expected A+ rate for the age group. Across the full sample, participants with a combination of SCD and OBJ in the memory domain showed a lower Aβ42/ptau181 ratio compared to those with neither SCD nor OBJ. Conclusions: The cluster characterized by participants with OBJ and concomitant SCD was enriched for amyloid pathology. [ABSTRACT FROM AUTHOR]

Published
2024
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27. A generalizable data-driven model of atrophy heterogeneity and progression in memory clinic settings.

Author

Baumeister, Hannah, Vogel, Jacob W, Insel, Philip S, Kleineidam, Luca, Wolfsgruber, Steffen, Stark, Melina, Gellersen, Helena M, Yakupov, Renat, Schmid, Matthias C, Lüsebrink, Falk, Brosseron, Frederic, Ziegler, Gabriel, Freiesleben, Silka D, Preis, Lukas, Schneider, Luisa-Sophie, Spruth, Eike J, Altenstein, Slawek, Lohse, Andrea, Fliessbach, Klaus, and Vogt, Ina R

Subjects
MILD cognitive impairment, ATROPHY, EXECUTIVE function, CEREBRAL atrophy, ALZHEIMER'S disease, ALZHEIMER'S patients
Abstract

Memory clinic patients are a heterogeneous population representing various aetiologies of pathological ageing. It is not known whether divergent spatiotemporal progression patterns of brain atrophy, as previously described in Alzheimer's disease patients, are prevalent and clinically meaningful in this group of older adults. To uncover distinct atrophy subtypes, we applied the Subtype and Stage Inference (SuStaIn) algorithm to baseline structural MRI data from 813 participants enrolled in the DELCODE cohort (mean ± standard deviation, age = 70.67 ± 6.07 years, 52% females). Participants were cognitively unimpaired (n = 285) or fulfilled diagnostic criteria for subjective cognitive decline (n = 342), mild cognitive impairment (n = 118) or dementia of the Alzheimer's type (n = 68). Atrophy subtypes were compared in baseline demographics, fluid Alzheimer's disease biomarker levels, the Preclinical Alzheimer Cognitive Composite (PACC-5) as well as episodic memory and executive functioning. PACC-5 trajectories over up to 240 weeks were examined. To test whether baseline atrophy subtype and stage predicted clinical trajectories before manifest cognitive impairment, we analysed PACC-5 trajectories and mild cognitive impairment conversion rates of cognitively unimpaired participants and those with subjective cognitive decline. Limbic-predominant and hippocampal-sparing atrophy subtypes were identified. Limbic-predominant atrophy initially affected the medial temporal lobes, followed by further temporal regions and, finally, the remaining cortical regions. At baseline, this subtype was related to older age, more pathological Alzheimer's disease biomarker levels, APOE ε4 carriership and an amnestic cognitive impairment. Hippocampal-sparing atrophy initially occurred outside the temporal lobe, with the medial temporal lobe spared up to advanced atrophy stages. This atrophy pattern also affected individuals with positive Alzheimer's disease biomarkers and was associated with more generalized cognitive impairment. Limbic-predominant atrophy, in all participants and in only unimpaired participants, was linked to more negative longitudinal PACC-5 slopes than observed in participants without or with hippocampal-sparing atrophy and increased the risk of mild cognitive impairment conversion. SuStaIn modelling was repeated in a sample from the Swedish BioFINDER-2 cohort. Highly similar atrophy progression patterns and associated cognitive profiles were identified. Cross-cohort model generalizability, at both the subject and the group level, was excellent, indicating reliable performance in previously unseen data. The proposed model is a promising tool for capturing heterogeneity among older adults at early at-risk states for Alzheimer's disease in applied settings. The implementation of atrophy subtype- and stage-specific end points might increase the statistical power of pharmacological trials targeting early Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Published
2024
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28. Differential Proteome Analysis Using 2D-DIGE

Author

May, Caroline, primary, Brosseron, Frederic, additional, Chartowski, Piotr, additional, Fuchs, Kristin, additional, Meyer, Helmut E., additional, Sitek, Barbara, additional, and Marcus, Katrin, additional

Published
2021
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29. Proteome Analysis with Classical 2D-PAGE

Author

May, Caroline, primary, Brosseron, Frederic, additional, Pfeiffer, Kathy, additional, Fuchs, Kristin, additional, Meyer, Helmut E., additional, Sitek, Barbara, additional, and Marcus, Katrin, additional

Published
2021
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30. Altered BOLD Signal Fluctuations in precuneus relate to inflammatory markers and vascular risk in the AD spectrum

Author

Maass, Anne, primary, Behrenbruch, Niklas, additional, Incesoy, Enise I, additional, Brosseron, Frederic, additional, Menze, Inga, additional, Bernal, Jose, additional, Hayek, Dayana, additional, Kleineidam, Luca, additional, Bürger, Katharina, additional, Fliessbach, Klaus, additional, Laske, Christoph, additional, Perneczky, Robert, additional, Peters, Oliver, additional, Priller, Josef, additional, Schneider, Anja, additional, Spottke, Annika, additional, Teipel, Stefan, additional, Wiltfang, Jens, additional, Wolfsgruber, Steffen, additional, Yakupov, Renat, additional, Wagner, Michael, additional, Jessen, Frank, additional, Duzel, Emrah, additional, Schreiber, Stefanie, additional, Heneka, Michael T., additional, and Ziegler, Gabriel, additional

Published
2023
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31. Locus coeruleus MRI contrast is associated with Complement factor C3b in cerebrospinal fluid

Author

Neumann, Laura, primary, Hayek, Dayana, additional, Sarkar, Mousumi, additional, Heinzinger, Nils, additional, Hämmerer, Dorothea, additional, Schneider, Anja, additional, Fließbach, Klaus, additional, Teipel, Stefan, additional, Spottke, Annika, additional, Brosseron, Frederic, additional, Jessen, Frank, additional, Düzel, Emrah, additional, Heneka, Michael T., additional, Maass, Anne, additional, and Betts, Matthew, additional

Published
2023
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32. NLRP3 inflammasome activation drives tau pathology

Author

Ising, Christina, Venegas, Carmen, Zhang, Shuangshuang, Scheiblich, Hannah, Schmidt, Susanne V., Vieira-Saecker, Ana, Schwartz, Stephanie, Albasset, Shadi, McManus, Róisín M., Tejera, Dario, Griep, Angelika, Santarelli, Francesco, Brosseron, Frederic, Opitz, Sabine, Stunden, James, Merten, Maximilian, Kayed, Rakez, Golenbock, Douglas T., Blum, David, Latz, Eicke, Buée, Luc, and Heneka, Michael T.

Published
2019
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34. 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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35. Single-value fMRI scores reflect both stage and risk across the Alzheimer's disease continuum

Author

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

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

Author

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

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

Author

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

Published
2023
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39. Symptomatic clusters related to amyloid positivity in cognitively unimpaired individuals

Author

Sannemann, Lena, primary, Bartels, Claudia, additional, Brosseron, Frederic, additional, Buerger, Katharina, additional, Fliessbach, Klaus, additional, Freiesleben, Silka Dawn, additional, Frommann, Ingo, additional, Glanz, Wenzel, additional, Heneka, Michael T., additional, Janowitz, Daniel, additional, Kilimann, Ingo, additional, Kleineidam, Luca, additional, Lammerding, Dominik, additional, Laske, Christoph, additional, Munk, Matthias H. J., additional, Perneczky, Robert, additional, Peters, Oliver, additional, Priller, Josef, additional, Rauchmann, Boris-Stephan, additional, Rostamzadeh, Ayda, additional, Roy-Kluth, Nina, additional, Schild, Ann-Katrin, additional, Schneider, Anja, additional, Schneider, Luisa-Sophie, additional, Spottke, Annika, additional, Spruth, Eike Jakob, additional, Teipel, Stefan, additional, Wagner, Michael, additional, Wiltfang, Jens, additional, Wolfsgruber, Steffen, additional, Duezel, Emrah, additional, and Jessen, Frank, additional

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

Author

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

Published
2023
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41. 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
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42. 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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43. Association of latent factors of neuroinflammation with Alzheimer's disease pathology and longitudinal cognitive decline.

Author

Teipel, Stefan J., Dyrba, Martin, Kleineidam, Luca, Brosseron, Frederic, Levin, Fedor, Bruno, Davide, Buerger, Katharina, Cosma, Nicoleta, Schneider, Luisa‐Sophie, Düzel, Emrah, Glanz, Wenzel, Fliessbach, Klaus, Janowitz, Daniel, Kilimann, Ingo, Laske, Christoph, Munk, Matthias H., Maier, Franziska, Peters, Oliver, Pomara, Nunzio, and Perneczky, Robert

Subjects
ALZHEIMER'S disease, PATHOLOGY, COGNITION disorders, CONFIRMATORY factor analysis, COMPLEMENT (Immunology)
Abstract

INTRODUCTION: We investigated the association of inflammatory mechanisms with markers of Alzheimer's disease (AD) pathology and rates of cognitive decline in the AD spectrum. METHODS: We studied 296 cases from the Deutsches Zentrum für Neurodegenerative Erkrankungen Longitudinal Cognitive Impairment and Dementia Study (DELCODE) cohort, and an extension cohort of 276 cases of the Alzheimer's Disease Neuroimaging Initiative study. Using Bayesian confirmatory factor analysis, we constructed latent factors for synaptic integrity, microglia, cerebrovascular endothelial function, cytokine/chemokine, and complement components of the inflammatory response using a set of inflammatory markers in cerebrospinal fluid. RESULTS: We found strong evidence for an association of synaptic integrity, microglia response, and cerebrovascular endothelial function with a latent factor of AD pathology and with rates of cognitive decline. We found evidence against an association of complement and cytokine/chemokine factors with AD pathology and rates of cognitive decline. DISCUSSION: Latent factors provided access to directly unobservable components of the neuroinflammatory response and their association with AD pathology and cognitive decline. [ABSTRACT FROM AUTHOR]

Published
2024
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44. 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
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45. Midlife occupational cognitive requirements protect cognitive function in old age by increasing cognitive reserve

Author

Kleineidam, Luca, primary, Wolfsgruber, Steffen, additional, Weyrauch, Anne-Sophie, additional, Zulka, Linn E., additional, Forstmeier, Simon, additional, Roeske, Sandra, additional, van den Bussche, Hendrik, additional, Kaduszkiewicz, Hanna, additional, Wiese, Birgitt, additional, Weyerer, Siegfried, additional, Werle, Jochen, additional, Fuchs, Angela, additional, Pentzek, Michael, additional, Brettschneider, Christian, additional, König, Hans-Helmut, additional, Weeg, Dagmar, additional, Bickel, Horst, additional, Luppa, Melanie, additional, Rodriguez, Francisca S., additional, Freiesleben, Silka Dawn, additional, Erdogan, Selin, additional, Unterfeld, Chantal, additional, Peters, Oliver, additional, Spruth, Eike J., additional, Altenstein, Slawek, additional, Lohse, Andrea, additional, Priller, Josef, additional, Fliessbach, Klaus, additional, Kobeleva, Xenia, additional, Schneider, Anja, additional, Bartels, Claudia, additional, Schott, Björn H., additional, Wiltfang, Jens, additional, Maier, Franziska, additional, Glanz, Wenzel, additional, Incesoy, Enise I., additional, Butryn, Michaela, additional, Düzel, Emrah, additional, Buerger, Katharina, additional, Janowitz, Daniel, additional, Ewers, Michael, additional, Rauchmann, Boris-Stephan, additional, Perneczky, Robert, additional, Kilimann, Ingo, additional, Görß, Doreen, additional, Teipel, Stefan, additional, Laske, Christoph, additional, Munk, Matthias H. J., additional, Spottke, Annika, additional, Roy, Nina, additional, Brosseron, Frederic, additional, Heneka, Michael T., additional, Ramirez, Alfredo, additional, Yakupov, Renat, additional, Scherer, Martin, additional, Maier, Wolfgang, additional, Jessen, Frank, additional, Riedel-Heller, Steffi G., additional, and Wagner, Michael, additional

Published
2022
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46. 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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47. Soluble TAM receptor biomarkers: Neuroprotection in AD neuroinflammation?"

Author

Brosseron, Frederic, primary, Maass, Anne, additional, Kleineidam, Luca, additional, Ravichandran, Kishore Aravind, additional, Peters, Oliver, additional, Priller, Josef, additional, Schneider, Anja, additional, Fließbach, Klaus, additional, Wiltfang, Jens, additional, Duzel, Emrah, additional, Buerger, Katharina, additional, Perneczky, Robert, additional, Teipel, Stefan, additional, Laske, Christoph, additional, Spottke, Annika, additional, Teunissen, Charlotte E., additional, Synofzik, Matthis, additional, Wagner, Michael, additional, Jessen, Frank, additional, Ramirez, Alfredo, additional, Ruiz, Agustin, additional, and Heneka, Michael T., additional

Published
2022
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48. Speed of cognitive decline in biomarker stratified SCD subgroups

Author

Jessen, Frank, primary, Kleineidam, Luca, additional, Wolfsgruber, Steffen, additional, Spottke, Annika, additional, Brosseron, Frederic, 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 Duzel, Emrah, additional

Published
2022
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49. 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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50. WITHDRAWN: Multi-centre Alzheimer's and Parkinson's disease immune biomarker verification study

Author

Brosseron, Frederic, Kolbe, Carl-Christian, Santarelli, Francesco, Carvalho, Stephanie, Antonell, Anna, Castro-Gomez, Sergio, Tacik, Pawel, Namasivayam, Aishwarya Alex, Mangone, Graziella, Schneider, Reinhard, Latz, Eicke, Wüllner, Ullrich, Svenningsson, Per, Sánchez-Valle, Raquel, Molinuevo, José Luis, Corvol, Jean-Christophe, and Heneka, Michael T.

Published
2023
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