Sofia Finsterwalder1, Naomi Vlegels2, Benno Gesierich1, Miguel Á Araque Caballero1,3, Nick A Weaver2, Nicolai Franzmeier1, Marios K Georgakis1, Marek J Konieczny1, Huiberdina L Koek4, Celeste M Karch5, Neill R Graff-Radford6, Stephen Salloway7, Hwamee Oh8, Ricardo F Allegri9, Jasmeer P Chhatwal10, Frank Jessen11,12, Emrah Düzel13,14, Laura Dobisch13,14, Coraline Metzger13,14,15, Oliver Peters16,17, Enise I Incesoy17, Josef Priller16,17, Eike J Spruth16,17, Anja Schneider11,18, Klaus Fließbach11,18, Katharina Buerger1,3, Daniel Janowitz1, Stefan J Teipel19,20, Ingo Kilimann19,20, Christoph Laske21,22, Martina Buchmann21,22, Michael T Heneka11,18, Frederic Brosseron11,18, Annika Spottke11,23, Nina Roy11, Birgit Ertl-Wagner24,25, Klaus Scheffler26, Sang Won Seo27,28,29,30,31, Yeshin Kim27,28,32, Duk L Na27,28,31,33, Hee Jin Kim27,28,31, Hyemin Jang27,28,31, Michael Ewers1, Johannes Levin3,34,35, Reinhold Schmidt36, Ofer Pasternak37, Martin Dichgans1,35, Geert Jan Biessels2, Marco Duering1,35. 1. Institute for Stroke and Dementia Research, University Hospital, LMU Munich, Munich, Germany. 2. Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands. 3. German Center for Neurodegenerative Diseases (DZNE), Munich, Germany. 4. Department of Geriatrics, University Medical Center Utrecht, Utrecht, the Netherlands. 5. Department of Psychiatry, Washington University in St. Louis, St. Louis, Missouri, USA. 6. Department of Neurology, Mayo Clinic Jacksonville, Jacksonville, Florida, USA. 7. Butler Hospital, Providence, Rhode Island, USA. 8. Department of Psychiatry and Human Behavior, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA. 9. Department of Cognitive Neurology, FLENI Institute for Neurological Research, Buenos Aires, Argentina. 10. Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. 11. German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany. 12. Department of Psychiatry, University of Cologne, Medical Faculty, Cologne, Germany. 13. German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany. 14. Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, Magdeburg, Germany. 15. Department of Psychiatry and Psychotherapy, Otto-von-Guericke University, Magdeburg, Germany. 16. German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany. 17. 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. 18. Department for Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany. 19. German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany. 20. Department of Psychosomatic Medicine, Rostock University Medical Center, Rostock, Germany. 21. German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany. 22. Section for Dementia Research, Hertie Institute for Clinical Brain Research and Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany. 23. Department of Neurology, University of Bonn, Bonn, Germany. 24. Institute of Clinical Radiology, University Hospital, LMU Munich, Munich, Germany. 25. Department of Medical Imaging, University of Toronto, Toronto, Canada. 26. Department for Biomedical Magnetic Resonance, University of Tübingen, Tübingen, Germany. 27. Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. 28. Neuroscience Center, Samsung Medical Center, Seoul, South Korea. 29. Department of Clinical Research Design and Evaluation, Samsung Advanced Institute of Health Sciences and Technology, Sungkyunkwan University, Seoul, South Korea. 30. Center for Imaging of Neurodegenerative Diseases, University of California, San Francisco, California, USA. 31. Samsung Alzheimer Research Center, Samsung Medical Center, Seoul, South Korea. 32. Department of Neurology, Kangwon National University Hospital, Kangwon National University College of Medicine, Chuncheon, South Korea. 33. Department of Health Sciences and Technology, Samsung Advanced Institute of Health Sciences and Technology, Sungkyunkwan University, Seoul, South Korea. 34. Department of Neurology, University Hospital, LMU Munich, Munich, Germany. 35. Munich Cluster for Systems Neurology (SyNergy), Munich, Germany. 36. Department of Neurology, Medical University of Graz, Graz, Austria. 37. Department of Psychiatry and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Abstract
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.
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.
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