Small vessel disease more than Alzheimer's disease determines diffusion MRI alterations in memory clinic patients
Dominantly Inherited Alzheimer Network (DIAN)* DELCODE study group* Alzheimer's Disease Neuroimaging Initiative (ADNI)* Utrecht VCI study group*
(2020) Alzheimer's & Dementia, volume 16, issue 11, pp. 1504 - 1514
(Article)
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
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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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Keywords: Alzheimer's disease, biomarker, cerebral small vessel disease, diffusion tensor imaging, free water imaging, white matter, Clinical Neurology, Geriatrics and Gerontology, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Health Policy, Developmental Neuroscience, Epidemiology, Journal Article
ISSN: 1552-5260
Publisher: John Wiley & Sons Inc.
Note: Funding Information: 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). Funding Information: 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. Publisher Copyright: © 2020 the Alzheimer's Association
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