Alzheimer's disease; biomarker; cerebral small vessel disease; diffusion tensor imaging; free water imaging; white matter; Adult; Aged; Alzheimer Disease/diagnostic imaging; Alzheimer Disease/pathology; Brain/diagnostic imaging; Brain/pathology; Cerebral Small Vessel Diseases/diagnostic imaging; Cerebral Small Vessel Diseases/pathology; Diffusion Magnetic Resonance Imaging; Female; Humans; Male; Middle Aged; Brain; Cerebral Small Vessel Diseases; Epidemiology; Health Policy; Developmental Neuroscience; Neurology (clinical); Geriatrics and Gerontology; Cellular and Molecular Neuroscience; Psychiatry and Mental Health
Abstract :
[en] INTRODUCTION: Microstructural alterations as assessed by diffusion tensor imaging (DTI) are key findings in both Alzheimer's disease (AD) and small vessel disease (SVD). We determined the contribution of each of these conditions to diffusion alterations.
METHODS: We studied six samples (N = 365 participants) covering the spectrum of AD and SVD, including genetically defined samples. We calculated diffusion measures from DTI and free water imaging. Simple linear, multivariable random forest, and voxel-based regressions were used to evaluate associations between AD biomarkers (amyloid beta, tau), SVD imaging markers, and diffusion measures.
RESULTS: SVD markers were strongly associated with diffusion measures and showed a higher contribution than AD biomarkers in multivariable analysis across all memory clinic samples. Voxel-wise analyses between tau and diffusion measures were not significant.
DISCUSSION: In memory clinic patients, the effect of SVD on diffusion alterations largely exceeds the effect of AD, supporting the value of diffusion measures as markers of SVD.
Disciplines :
Neurology
Author, co-author :
Finsterwalder, Sofia ✱; Institute for Stroke and Dementia Research, University Hospital, LMU Munich, Munich, Germany
Vlegels, Naomi ✱; Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
Gesierich, Benno; Institute for Stroke and Dementia Research, University Hospital, LMU Munich, Munich, Germany
Araque Caballero, Miguel Á; Institute for Stroke and Dementia Research, University Hospital, LMU Munich, Munich, Germany ; German Center for Neurodegenerative Diseases (DZNE), Munich, Germany
Weaver, Nick A; Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
Franzmeier, Nicolai; Institute for Stroke and Dementia Research, University Hospital, LMU Munich, Munich, Germany
Georgakis, Marios K; Institute for Stroke and Dementia Research, University Hospital, LMU Munich, Munich, Germany
Konieczny, Marek J; Institute for Stroke and Dementia Research, University Hospital, LMU Munich, Munich, Germany
Koek, Huiberdina L; Department of Geriatrics, University Medical Center Utrecht, Utrecht, the Netherlands
Dominantly Inherited Alzheimer Network (DIAN)
Karch, Celeste M; Department of Psychiatry, Washington University in St. Louis, St. Louis, Missouri, USA
Graff-Radford, Neill R; Department of Neurology, Mayo Clinic Jacksonville, Jacksonville, Florida, USA
Salloway, Stephen; Butler Hospital, Providence, Rhode Island, USA
Oh, Hwamee; Department of Psychiatry and Human Behavior, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA
Allegri, Ricardo F; Department of Cognitive Neurology, FLENI Institute for Neurological Research, Buenos Aires, Argentina
Chhatwal, Jasmeer P; Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
DELCODE study group
Jessen, Frank; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany ; Department of Psychiatry, University of Cologne, Medical Faculty, Cologne, Germany
Düzel, Emrah; German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany ; Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, Magdeburg, Germany
Dobisch, Laura; German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany ; Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, Magdeburg, Germany
Metzger, Coraline; German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany ; Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, Magdeburg, Germany ; Department of Psychiatry and Psychotherapy, Otto-von-Guericke University, Magdeburg, Germany
Peters, Oliver; German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany ; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Psychiatry and Psychotherapy, Berlin, Germany
Incesoy, Enise I; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Psychiatry and Psychotherapy, Berlin, Germany
Priller, Josef; German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany ; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Psychiatry and Psychotherapy, Berlin, Germany
Spruth, Eike J; German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany ; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Psychiatry and Psychotherapy, Berlin, Germany
Schneider, Anja; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany ; Department for Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany
Fließbach, Klaus; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany ; Department for Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany
Buerger, Katharina; Institute for Stroke and Dementia Research, University Hospital, LMU Munich, Munich, Germany ; German Center for Neurodegenerative Diseases (DZNE), Munich, Germany
Janowitz, Daniel; Institute for Stroke and Dementia Research, University Hospital, LMU Munich, Munich, Germany
Teipel, Stefan J; German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany ; Department of Psychosomatic Medicine, Rostock University Medical Center, Rostock, Germany
Kilimann, Ingo; German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany ; Department of Psychosomatic Medicine, Rostock University Medical Center, Rostock, Germany
Laske, Christoph; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany ; Section for Dementia Research, Hertie Institute for Clinical Brain Research and Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany
Buchmann, Martina; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany ; Section for Dementia Research, Hertie Institute for Clinical Brain Research and Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany
HENEKA, Michael ; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany ; Department for Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany
Brosseron, Frederic; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany ; Department for Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany
Spottke, Annika; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany ; Department of Neurology, University of Bonn, Bonn, Germany
Roy, Nina; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
Ertl-Wagner, Birgit; Institute of Clinical Radiology, University Hospital, LMU Munich, Munich, Germany ; Department of Medical Imaging, University of Toronto, Toronto, Canada
Scheffler, Klaus; Department for Biomedical Magnetic Resonance, University of Tübingen, Tübingen, Germany
Seo, Sang Won; Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea ; Neuroscience Center, Samsung Medical Center, Seoul, South Korea ; Department of Clinical Research Design and Evaluation, Samsung Advanced Institute of Health Sciences and Technology, Sungkyunkwan University, Seoul, South Korea ; Center for Imaging of Neurodegenerative Diseases, University of California, San Francisco, California, USA ; Samsung Alzheimer Research Center, Samsung Medical Center, Seoul, South Korea
Kim, Yeshin; Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea ; Neuroscience Center, Samsung Medical Center, Seoul, South Korea ; Department of Neurology, Kangwon National University Hospital, Kangwon National University College of Medicine, Chuncheon, South Korea
Na, Duk L; Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea ; Neuroscience Center, Samsung Medical Center, Seoul, South Korea ; Samsung Alzheimer Research Center, Samsung Medical Center, Seoul, South Korea ; Department of Health Sciences and Technology, Samsung Advanced Institute of Health Sciences and Technology, Sungkyunkwan University, Seoul, South Korea
Kim, Hee Jin; Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea ; Neuroscience Center, Samsung Medical Center, Seoul, South Korea ; Samsung Alzheimer Research Center, Samsung Medical Center, Seoul, South Korea
Jang, Hyemin; Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea ; Neuroscience Center, Samsung Medical Center, Seoul, South Korea ; Samsung Alzheimer Research Center, Samsung Medical Center, Seoul, South Korea
Ewers, Michael; Institute for Stroke and Dementia Research, University Hospital, LMU Munich, Munich, Germany
Levin, Johannes; German Center for Neurodegenerative Diseases (DZNE), Munich, Germany ; Department of Neurology, University Hospital, LMU Munich, Munich, Germany ; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
Schmidt, Reinhold; Department of Neurology, Medical University of Graz, Graz, Austria
Pasternak, Ofer; Department of Psychiatry and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
Dichgans, Martin; Institute for Stroke and Dementia Research, University Hospital, LMU Munich, Munich, Germany ; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
Biessels, Geert Jan; Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
Duering, Marco; Institute for Stroke and Dementia Research, University Hospital, LMU Munich, Munich, Germany ; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
The study was funded by a cross‐border grant from the Alzheimer Forschung Initiative e.V. (#16018CB)/Alzheimer Nederland AN WE.03‐2016‐1. BG and MDu were supported by the German Research Foundation (DU1626/1‐1). The research of GJB is also supported by VICI grant 918.16.616 from NWO, the Netherlands Organization for Scientific Research. DIAN: Data collection and sharing for this project was supported by The Dominantly Inherited Alzheimer's Network (DIAN, U19AG032438) funded by the National Institute on Aging (NIA), the German Center for Neurodegenerative Diseases (DZNE), Raul Carrea Institute for Neurological Research (FLENI). Partial support by the Research and Development Grants for Dementia from Japan Agency for Medical Research and Development, AMED, and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI). This article has been reviewed by DIAN Study investigators for scientific content and consistency of data interpretation with previous DIAN Study publications. DELCODE: The DELCODE study was funded by the German Center for Neurodegenerative Diseases (DZNE), Study‐ID: BN012DZNE. We acknowledge support from the Max‐Delbrück‐Centrum für Molekulare Medizin in der Helmholtz‐Gemeinschaft (MDC) and the Freie Universität Berlin Center for Cognitive Neuroscience Berlin (CCNB). ADNI: Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI; National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH‐12‐2‐0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol‐Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann‐La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC; Johnson & Johnson Pharmaceutical Research & Development LLC; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health ( www.fnih.org ). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. SVCI: This research was funded by Research of Korea Centers for Disease Control and Prevention (2018‐ER6203‐01).We would like to thank all the researchers and the support staff from the DIAN (https://dian.wustl.edu/wp-content/uploads/2019/04/DIAN-TU-Publications_Acknowledgement_V14.pdf), DELCODE, ADNI, Utrecht VCI study group, Seoul VCI study group, and CADASIL study for their contributions to the present study. Investigators within DIAN, DELCODE, and ADNI contributed to the design and implementation of the respective studies and/or provided data but did not participate in analysis or writing of this report. A complete listing of the DIAN consortium and the DELCODE study group can be found in Tables S9 and 10 in supporting information and ADNI investigators at http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf. Members of the Utrecht VCI study group involved in the present study (in alphabetical order by department): University Medical Center Utrecht, the Netherlands, Department of Neurology: E. van den Berg, J. M. Biesbroek, M. Brundel, W. H. Bouvy, L. G. Exalto, C. J. M. Frijns, O. Groeneveld, S. M. Heringa, R. Heinen, N. Kalsbeek, L. J. Kappelle, J. H. Verwer; Department of Radiology/Image Sciences Institute: J. de Bresser, H. J. Kuijf, A. Leemans, P. R. Luijten, M. A. Viergever, K. L. Vincken, J. J. M. Zwanenburg; Department of Geriatrics: H. L. Koek; Hospital Diakonessenhuis Zeist, the Netherlands: M. Hamaker, R. Faaij, M. Pleizier, E. Vriens.
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