[en] Several Alzheimer's disease (AD) atrophy subtypes were identified, but their brain network properties are unclear. We analyzed data from two independent datasets, including 166 participants (103 AD/63 controls) from the DZNE-longitudinal cognitive impairment and dementia study and 151 participants (121 AD/30 controls) from the AD neuroimaging initiative cohorts, aiming to identify differences between AD atrophy subtypes in resting-state functional magnetic resonance imaging intra-network connectivity (INC) and global and nodal network properties. Using a data-driven clustering approach, we identified four AD atrophy subtypes with differences in functional connectivity, accompanied by clinical and biomarker alterations, including a medio-temporal-predominant (S-MT), a limbic-predominant (S-L), a diffuse (S-D), and a mild-atrophy (S-MA) subtype. S-MT and S-D showed INC reduction in the default mode, dorsal attention, visual and limbic network, and a pronounced reduction of "global efficiency" and decrease of the "clustering coefficient" in parietal and temporal lobes. Despite severe atrophy in limbic areas, the S-L exhibited only marginal global network but substantial nodal network failure. S-MA, in contrast, showed limited impairment in clinical and cognitive scores but pronounced global network failure. Our results contribute toward a better understanding of heterogeneity in AD with the detection of distinct differences in functional connectivity networks accompanied by CSF biomarker and cognitive differences in AD subtypes.
Disciplines :
Neurology
Author, co-author :
Rauchmann, Boris-Stephan; Department of Radiology, University Hospital, LMU, Munich 81377, Germany ; Department of Psychiatry and Psychotherapy, University Hospital, LMU, Munich 80336, Germany
Ersoezlue, Ersin; Department of Psychiatry and Psychotherapy, University Hospital, LMU, Munich 80336, Germany
Stoecklein, Sophia; Department of Radiology, University Hospital, LMU, Munich 81377, Germany
Keeser, Daniel; Department of Radiology, University Hospital, LMU, Munich 81377, Germany ; Department of Psychiatry and Psychotherapy, University Hospital, LMU, Munich 80336, Germany
Brosseron, Frederic; German Center for Neurodegenerative Diseases (DZNE), Bonn 53127, Germany ; Department for Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn 53127, Germany
Buerger, Katharina; German Center for Neurodegenerative Diseases (DZNE), Munich 81377, Germany ; Institute for Stroke and Dementia Research (ISD), University Hospital, LMU, Munich 81377, Germany
Dechent, Peter; MR-Research in Neurology and Psychiatry, Georg-August-University Goettingen, Göttingen 37077, Germany
Dobisch, Laura; German Center for Neurodegenerative Diseases (DZNE), Magdeburg 39120, Germany
Ertl-Wagner, Birgit; Department of Radiology, University Hospital, LMU, Munich 81377, Germany ; Department of Medical Imaging, The Hospital for Sick Children, University of Toronto, Toronto, Ontario M5T 1W7, Canada
Fliessbach, Klaus; German Center for Neurodegenerative Diseases (DZNE), Bonn 53127, Germany ; Department for Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn 53127, Germany
Haynes, John Dylan; Bernstein Center for Computational Neuroscience, Charité, Berlin 10115, Germany
HENEKA, Michael ; German Center for Neurodegenerative Diseases (DZNE), Bonn 53127, Germany ; Department for Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn 53127, Germany
Incesoy, Enise I; German Center for Neurodegenerative Diseases (DZNE), Berlin 10117, Germany ; Charité - Universitaetsmedizin Berlin, Institute of Psychiatry and Psychotherapy, Berlin 10117, Germany
Janowitz, Daniel; Institute for Stroke and Dementia Research (ISD), University Hospital, LMU, Munich 81377, Germany
Kilimann, Ingo; German Center for Neurodegenerative Diseases (DZNE), Rostock 18147, Germany ; Department of Psychosomatic Medicine, Rostock University Medical Center, Rostock 18147
Laske, Christoph; German Center for Neurodegenerative Diseases (DZNE), Tuebingen 72076, Germany ; Section for Dementia Research, Hertie Institute for Clinical Brain Research and Department of Psychiatry and Psychotherapy, University of Tuebingen, Tuebingen 72076, Germany
Metzger, Coraline D; German Center for Neurodegenerative Diseases (DZNE), Magdeburg 39120, Germany ; Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, Magdeburg 39120, Germany ; Department of Psychiatry and Psychotherapy, Otto-von-Guericke University, Magdeburg 39120, Germany
Munk, Matthias H; German Center for Neurodegenerative Diseases (DZNE), Tuebingen 72076, Germany ; Section for Dementia Research, Hertie Institute for Clinical Brain Research and Department of Psychiatry and Psychotherapy, University of Tuebingen, Tuebingen 72076, Germany
Peters, Oliver; German Center for Neurodegenerative Diseases (DZNE), Berlin 10117, Germany ; Charité - Universitaetsmedizin Berlin, Institute of Psychiatry and Psychotherapy, Berlin 10117, Germany
Priller, Josef; German Center for Neurodegenerative Diseases (DZNE), Berlin 10117, Germany ; Department of Psychiatry and Psychotherapy, Charité, Berlin 10117, Germany
Ramirez, Alfredo; German Center for Neurodegenerative Diseases (DZNE), Bonn 53127, Germany ; Department for Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn 53127, Germany ; Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry, University of Cologne, Medical Faculty, Cologne 50937, Germany
Roeske, Sandra; German Center for Neurodegenerative Diseases (DZNE), Bonn 53127, Germany
Roy, Nina; German Center for Neurodegenerative Diseases (DZNE), Bonn 53127, Germany
Scheffler, Klaus; Department for Biomedical Magnetic Resonance, University of Tuebingen, Tuebingen 72076, Germany
Schneider, Anja; German Center for Neurodegenerative Diseases (DZNE), Bonn 53127, Germany ; Department for Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn 53127, Germany
Spottke, Annika; German Center for Neurodegenerative Diseases (DZNE), Bonn 53127, Germany ; Department of Neurology, University of Bonn, Bonn 53127, Germany
Spruth, Eike Jakob; German Center for Neurodegenerative Diseases (DZNE), Berlin 10117, Germany ; Department of Psychiatry and Psychotherapy, Charité, Berlin 10117, Germany
Teipel, Stefan; German Center for Neurodegenerative Diseases (DZNE), Rostock 18147, Germany ; Department of Psychosomatic Medicine, Rostock University Medical Center, Rostock 18147
Tscheuschler, Maike; Department of Psychiatry, University of Cologne, Medical Faculty, Cologne 50924, Germany
Vukovich, Ruth; Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, University of Goettingen, Goettingen 37075, Germany
Wagner, Michael; German Center for Neurodegenerative Diseases (DZNE), Bonn 53127, Germany ; Department for Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn 53127, Germany
Wiltfang, Jens; Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, University of Goettingen, Goettingen 37075, Germany ; German Center for Neurodegenerative Diseases (DZNE), Goettingen 37075, Germany ; Neurosciences and Signaling Group, Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, Aveiro 3810-193, Portugal
Yakupov, Renat; German Center for Neurodegenerative Diseases (DZNE), Magdeburg 39120, Germany
Duezel, Emrah; German Center for Neurodegenerative Diseases (DZNE), Magdeburg 39120, Germany ; Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, Magdeburg 39120, Germany
Jessen, Frank; German Center for Neurodegenerative Diseases (DZNE), Bonn 53127, Germany ; Department of Psychiatry, University of Cologne, Medical Faculty, Cologne 50924, Germany ; Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne 50931, Germany
Perneczky, Robert; Department of Psychiatry and Psychotherapy, University Hospital, LMU, Munich 80336, Germany ; German Center for Neurodegenerative Diseases (DZNE), Munich 81377, Germany ; Munich Cluster for Systems Neurology (SyNergy), Munich 81377, Germany ; Ageing Epidemiology (AGE) Research Unit, School of Public Health, Imperial College, London W6 8RP, UK
DELCODE study group and the Alzheimer's Disease Neuroimaging Initiative (ADNI)
Alzheimer's Disease Neuroimaging Initiative National Institute on Aging National Institute of Biomedical Imaging and Bioengineering Alzheimer's Drug Discovery Foundation Amorfix Life Sciences Ltd Bayer HealthCare Takeda Pharmaceutical Company Canadian Institutes of Health Research National Institutes of Health
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