Jessica Alber, University of Rhode Island
Suvarna Alladi, National Institute of Mental Health and Neurosciences, India
Hee-Joon Bae, Seoul National University, South Korea
David A. Barton, University of Melbourne, Australia
Laurel A. Beckett, University of California - Davis
Joanne M. Bell, Syneos Health,
Sara E. Berman, University of Wisconsin - Madison
Geert Jan Biessels, University Medical Center Utrecht, The Netherlands
Sandra E. Black, University of Toronto, Canada
Isabelle Bos, Maastricht University, The Netherlands
Gene L. Bowman, Harvard University
Emanuele Brai, Culham Science Centre, UK
Adam M. Brickman, Columbia University
Brandy L. Callahan, University of Calgary, Canada
Roderick A. Corriveau, University of Calgary, Canada
Silvia Fossati, New York University
Rebecca F. Gottesman, Johns Hopkins University
Deborah R. Gustafson, State University of New York
Vladimir Hachinski, Western University, Canada
Kathleen M. Hayden, Wake Forest University
Alex M. Helman, University of KentuckyFollow
Timothy M. Hughes, Wake Forest University
Jeremy D. Isaacs, St. George’s University of London, UK
Angela L. Jefferson, Vanderbilt University
Sterling C. Johnson, University of Wisconsin - Madison
Alifiya Kapasi, Rush Alzheimer’s Disease Center
Silke Kern, University of Gothenburg, Sweden
Jay C. Kwon, Changwon Fatima Hospital, South Korea
Juraj Kukolja, Helios University, Germany
Athene Lee, Brown University
Brittani R. Price, University of KentuckyFollow
Donna M. Wilcock, University of KentuckyFollow


White matter hyperintensities (WMHs) are frequently seen on brain magnetic resonance imaging scans of older people. Usually interpreted clinically as a surrogate for cerebral small vessel disease, WMHs are associated with increased likelihood of cognitive impairment and dementia (including Alzheimer's disease [AD]). WMHs are also seen in cognitively healthy people. In this collaboration of academic, clinical, and pharmaceutical industry perspectives, we identify outstanding questions about WMHs and their relation to cognition, dementia, and AD. What molecular and cellular changes underlie WMHs? What are the neuropathological correlates of WMHs? To what extent are demyelination and inflammation present? Is it helpful to subdivide into periventricular and subcortical WMHs? What do WMHs signify in people diagnosed with AD? What are the risk factors for developing WMHs? What preventive and therapeutic strategies target WMHs? Answering these questions will improve prevention and treatment of WMHs and dementia.

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Notes/Citation Information

Published in Alzheimer's & Dementia: Translational Research & Clinical Interventions, v. 5, p. 107-117.

© 2019 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer’s Association.

This is an open access article under the CC BY-NC-ND license (

Due to the large number of authors, only the first 30 and the authors affiliated with the University of Kentucky are listed in the author section above. For the complete list of authors, please download this article or visit:

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Funding Information

D.A.B. is funded by National Health and Medical Research Council (Australia). S.E.B. has funding from National Institutes of Health (NIH)/National Institute on Aging (NIA) (grant F30AG054115). G.J.B. acknowledges support from Vici (grant 918.16.616), from ZonMw, from The Netherlands Organisation for Health Research and Development, and from the Netherlands CardioVascular Research Initiative: the Dutch Heart Foundation (CVON 2012-06 Heart Brain Connection). G.L.B. reports US NIH/NIA funding. B.L.C. holds a Canada Research Chair. S.F. has NIH funding. T.M.H., K.M.H. and S.N.L. were supported by funding from the NIH (P30 AG049638). J.K. is grateful for the support of the Marga and Walter Boll Foundation, Kerpen, Germany. M.C.P. has NIH and US DoD funding. C.E.S. was funded by National Institute on Aging (grant number F31 AG054084). A.M.T. was funded by Israel Science Foundation (grant 1353/11). C.W. is funded by the Weston Brain Institute, Canadian Institutes of Health Research (CIHR) and Cure Alzheimer's Fund. A.H.H. has funding from UK MRC (MR/R005567/1), Alzheimer's Society (UK), and ADDF (Ref. 20140901).