University of Oulu

Tuovinen, T., Kananen, J., Rajna, Z. et al. The variability of functional MRI brain signal increases in Alzheimer’s disease at cardiorespiratory frequencies. Sci Rep 10, 21559 (2020).

The variability of functional MRI brain signal increases in Alzheimer’s disease at cardiorespiratory frequencies

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Author: Tuovinen, Timo1,2; Kananen, Janne1,2; Rajna, Zalan1,3;
Organizations: 1Oulu Functional Neuroimaging, Medical Imaging, Physics and Technology, University of Oulu, Oulu, Finland
2Medical Research Center, Oulu University Hospital, Oulu, Finland
3Center for Machine Vision and Signal Analysis, University of Oulu, Oulu, Finland
4Center for Life Course Health Research, University of Oulu, Oulu, Finland
5Department of Neurology, Hyvinkää Hospital, Helsinki University Hospital, Hyvinkää, Finland
6Department of Diagnostic Radiology, Helsinki University Hospital, Helsinki, Finland
7Research Unit of Clinical Neuroscience, Neurology, University of Oulu, Oulu, Finland
8Department of Radiology, Medical Physics, Medical Center ‑ University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
9Department of Radiology, Cumming School of Medicine, University of Calgary, Calgary, Canada
10Department of Paediatrics, Cumming School of Medicine, University of Calgary, Calgary, Canada
11Hotchkiss Brain Institute and Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, Canada
12Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, NY, USA
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 7.4 MB)
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Language: English
Published: Springer Nature, 2020
Publish Date: 2021-01-05


Biomarkers sensitive to prodromal or early pathophysiological changes in Alzheimer’s disease (AD) symptoms could improve disease detection and enable timely interventions. Changes in brain hemodynamics may be associated with the main clinical AD symptoms. To test this possibility, we measured the variability of blood oxygen level-dependent (BOLD) signal in individuals from three independent datasets (totaling 80 AD patients and 90 controls). We detected a replicable increase in brain BOLD signal variability in the AD populations, which constituted a robust biomarker for clearly differentiating AD cases from controls. Fast BOLD scans showed that the elevated BOLD signal variability in AD arises mainly from cardiovascular brain pulsations. Manifesting in abnormal cerebral perfusion and cerebrospinal fluid convection, present observation presents a mechanism explaining earlier observations of impaired glymphatic clearance associated with AD in humans.

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Series: Scientific reports
ISSN: 2045-2322
ISSN-E: 2045-2322
ISSN-L: 2045-2322
Volume: 10
Issue: 1
Article number: 21559
DOI: 10.1038/s41598-020-77984-1
Type of Publication: A1 Journal article – refereed
Field of Science: 3112 Neurosciences
3124 Neurology and psychiatry
Funding: This work was supported by grants from Finnish Academy grants 275352, 314497 (V.Ki.), Jane and Aatos Erkko Foundation (V.Ki.), KEVO grants from Oulu University Hospital (V.Ki.), DFG cluster BrainLinks-BrainTools EXC-1086 (P.L.), Epilepsy Research Foundation (J.Ka.), Finnish Cultural Foundation, North Ostrobothnia Regional Fund (J.Ka.), Orion Research Foundation sr (J.Ka., T.T.), Tauno Tönning Foundation (J.Ka.). The University of Oulu Scholarship Foundation (J.Ka.), Medical Research Center (MRC)-Oulu (J.Ka.), Maire Taponen Foundation sr (J.Ka.), Finnish Brain Foundation sr (J.Ka.), Instrumentarium Science Foundation sr (J.Ka.), The Finnish Medical Foundation (J.L., T.T.), Yrjö Jahnsson's Foundation (J.L.), The Finnish Medical Society Duodecim Oulu (T.T.). 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 ( 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.
Academy of Finland Grant Number: 275352
Detailed Information: 275352 (Academy of Finland Funding decision)
314497 (Academy of Finland Funding decision)
Copyright information: © The Authors 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit