White matter hyperintensities in vascular contributions to cognitive impairment and dementia (VCID): Knowledge gaps and opportunities

Jessica Alber, Suvarna Alladi, Hee Joon Bae, David A. Barton, Laurel A. Beckett, Joanne M. Bell, Sara E. Berman, Geert Jan Biessels, Sandra E. Black, Isabelle Bos, Gene L. Bowman, Emanuele Brai, Adam M. Brickman, Brandy L. Callahan, Roderick A. Corriveau, Silvia Fossati, Rebecca F. Gottesman, Deborah R. Gustafson, Vladimir Hachinski, Kathleen M. HaydenAlex M. Helman, Timothy M. Hughes, Jeremy D. Isaacs, Angela L. Jefferson, Sterling C. Johnson, Alifiya Kapasi, Silke Kern, Jay C. Kwon, Juraj Kukolja, Athene Lee, Samuel N. Lockhart, Anne Murray, Katie E. Osborn, Melinda C. Power, Brittani R. Price, Hanneke F.M. Rhodius-Meester, Jacqueline A. Rondeau, Allyson C. Rosen, Douglas L. Rosene, Julie A. Schneider, Henrieta Scholtzova, C. Elizabeth Shaaban, Narlon C.B.S. Silva, Heather M. Snyder, Walter Swardfager, Aron M. Troen, Susanne J. van Veluw, Prashanthi Vemuri, Anders Wallin, Cheryl Wellington, Donna M. Wilcock, Sharon Xiangwen Xie, Atticus H. Hainsworth*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

198 Scopus citations

Abstract

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.

Original languageAmerican English
Pages (from-to)107-117
Number of pages11
JournalAlzheimer's and Dementia: Translational Research and Clinical Interventions
Volume5
DOIs
StatePublished - 2019

Bibliographical note

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 ).

Funding Information:
Declarations of Interest: D.A.B. is the director of NeuroTrials Victoria Pty Ltd and has undertaken clinical trials for Roche, Alkermes, Otsuka, Lundbeck, and Janssen. G.J.B. has received speaker fees from Eisai and research support from Boehringer-Ingelheim . All compensation for these services is transferred to his employer, the University Medical Center Utrecht. G.L.B. is an unpaid scientific advisory board member of the PROPAG-AGEING EU Horizon 2020 initiative. R.A.C. is an employee of National Institute of Neurological Disorders and Stroke. J.D.I. has attended an advisory board for Biogen , is a principal investigator on clinical trials, and outside of the submitted work, was sponsored and funded by Roche and Merck . K.E.O. is funded by National Institutes of Health ( F32AG058395 ). C.W. is a member of the Canadian Institutes of Health Research–funded Canadian Consortium for Neurodegeneration in Aging. A.H.H. has received honoraria from Eli Lilly and the National Institute of Aging and is chair of the Dementias Platform UK Vascular Experimental Medicine group. All other authors declare they have no conflicts to disclose.

Funding Information:
Declarations of Interest: D.A.B. is the director of NeuroTrials Victoria Pty Ltd and has undertaken clinical trials for Roche, Alkermes, Otsuka, Lundbeck, and Janssen. G.J.B. has received speaker fees from Eisai and research support from Boehringer-Ingelheim. All compensation for these services is transferred to his employer, the University Medical Center Utrecht. G.L.B. is an unpaid scientific advisory board member of the PROPAG-AGEING EU Horizon 2020 initiative. R.A.C. is an employee of National Institute of Neurological Disorders and Stroke. J.D.I. has attended an advisory board for Biogen, is a principal investigator on clinical trials, and outside of the submitted work, was sponsored and funded by Roche and Merck. K.E.O. is funded by National Institutes of Health (F32AG058395). C.W. is a member of the Canadian Institutes of Health Research–funded Canadian Consortium for Neurodegeneration in Aging. A.H.H. has received honoraria from Eli Lilly and the National Institute of Aging and is chair of the Dementias Platform UK Vascular Experimental Medicine group. All other authors declare they have no conflicts to disclose.The authors are grateful to the Alzheimers Association and to The Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment for hosting the event at Alzheimer's Association International Conference 2017, where this Perspective originated. The authors apologize to their colleagues worldwide whose excellent publications they have failed to cite, owing to the reference limit of the journal. Where two citations were relevant, the authors have, as a rule, included only the more recent one. 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). The content is solely the responsibility of the authors and does not necessarily represent the official views of any funders. The funding sources had no involvement in preparation of the article, in the writing of the manuscript, and in the decision to submit the manuscript for publication.

Publisher Copyright:
© 2019 The Authors

Keywords

  • Leukoaraiosis
  • Small vessel disease
  • Vascular cognitive impairment
  • Vascular dementia
  • White matter lesions

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