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. Hayden; Alex 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

doi:10.1016/j.trci.2019.02.001

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. Hayden

Alex 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

Physiology

Research output: Contribution to journal › Short survey › peer-review

358 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 language	English
Pages (from-to)	107-117
Number of pages	11
Journal	Alzheimer's and Dementia: Translational Research and Clinical Interventions
Volume	5
DOIs	https://doi.org/10.1016/j.trci.2019.02.001
State	Published - 2019

Bibliographical note

Publisher Copyright:
© 2019 The Authors

Funding

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 ). 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. 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.

Funders	Funder number
NIH National Institute of Child Health and Human Development National Center for Medical Rehabilitation Research
Alzheimer's Society
Merck
Norges Idrettshøgskole
Dutch Heart Foundation
Boehringer-Ingelheim
Biogen IDEC
National Institutes of Health (NIH)
Australian National Health and Medical Research Council
Roche Canada
ZonMw Memorabel
Cure Alzheimer's Fund
Weston Brain Institute
Canadian Institutes of Health Research
U.S. Department of Defense
UK Industrial Decarbonization Research and Innovation Centre
National Institute of General Medical Sciences DP2GM119177 Sophie Dumont National Institute of General Medical Sciences	T32GM008692
Alzheimer's Drug Discovery Foundation	Ref. 20140901, 20140901
US-Israel Binational Science Foundation	1353/11
National Institute on Aging	918.16.616, P30AG010124, F31AG054084, P30AG028383, P30AG010129, F32AG058395, P30AG062715, P30AG049638, P50AG033514, F30AG054115
Institute of Neurological Disorders and Stroke National Advisory Neurological Disorders and Stroke Council	R01NS017950, R01NS104127
Eunice Kennedy Shriver National Institute of Child Health and Human Development	U54HD083211
CVON 2012-06 Heart Brain Connection	P30 AG049638
UK Medical Research Council, Engineering and Physical Sciences Research Council	MR/R005567/1
Marga und Walter Boll-Stiftung	F31 AG054084

Keywords

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

ASJC Scopus subject areas

Clinical Neurology
Psychiatry and Mental health

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.trci.2019.02.001

Cite this

Alber, J., Alladi, S., Bae, H. J., Barton, D. A., Beckett, L. A., Bell, J. M., Berman, S. E., Biessels, G. J., Black, S. E., Bos, I., Bowman, G. L., Brai, E., Brickman, A. M., Callahan, B. L., Corriveau, R. A., Fossati, S., Gottesman, R. F., Gustafson, D. R., Hachinski, V., ... Hainsworth, A. H. (2019). White matter hyperintensities in vascular contributions to cognitive impairment and dementia (VCID): Knowledge gaps and opportunities. Alzheimer's and Dementia: Translational Research and Clinical Interventions, 5, 107-117. https://doi.org/10.1016/j.trci.2019.02.001

@article{0e3631aa364240308f6a68fad1d1c5d9,

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

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.",

keywords = "Leukoaraiosis, Small vessel disease, Vascular cognitive impairment, Vascular dementia, White matter lesions",

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

note = "Publisher Copyright: {\textcopyright} 2019 The Authors",

year = "2019",

doi = "10.1016/j.trci.2019.02.001",

language = "English",

volume = "5",

pages = "107--117",

}

Alber, J, Alladi, S, Bae, HJ, Barton, DA, Beckett, LA, Bell, JM, Berman, SE, Biessels, GJ, Black, SE, Bos, I, Bowman, GL, Brai, E, Brickman, AM, Callahan, BL, Corriveau, RA, Fossati, S, Gottesman, RF, Gustafson, DR, Hachinski, V, Hayden, KM, Helman, AM, Hughes, TM, Isaacs, JD, Jefferson, AL, Johnson, SC, Kapasi, A, Kern, S, Kwon, JC, Kukolja, J, Lee, A, Lockhart, SN, Murray, A, Osborn, KE, Power, MC, Price, BR, Rhodius-Meester, HFM, Rondeau, JA, Rosen, AC, Rosene, DL, Schneider, JA, Scholtzova, H, Shaaban, CE, Silva, NCBS, Snyder, HM, Swardfager, W, Troen, AM, van Veluw, SJ, Vemuri, P, Wallin, A, Wellington, C, Wilcock, DM, Xie, SX & Hainsworth, AH 2019, 'White matter hyperintensities in vascular contributions to cognitive impairment and dementia (VCID): Knowledge gaps and opportunities', Alzheimer's and Dementia: Translational Research and Clinical Interventions, vol. 5, pp. 107-117. https://doi.org/10.1016/j.trci.2019.02.001

White matter hyperintensities in vascular contributions to cognitive impairment and dementia (VCID): Knowledge gaps and opportunities. / Alber, Jessica; Alladi, Suvarna; Bae, Hee Joon et al.
In: Alzheimer's and Dementia: Translational Research and Clinical Interventions, Vol. 5, 2019, p. 107-117.

Research output: Contribution to journal › Short survey › peer-review

TY - JOUR

T1 - White matter hyperintensities in vascular contributions to cognitive impairment and dementia (VCID)

T2 - Knowledge gaps and opportunities

AU - Alber, Jessica

AU - Alladi, Suvarna

AU - Bae, Hee Joon

AU - Barton, David A.

AU - Beckett, Laurel A.

AU - Bell, Joanne M.

AU - Berman, Sara E.

AU - Biessels, Geert Jan

AU - Black, Sandra E.

AU - Bos, Isabelle

AU - Bowman, Gene L.

AU - Brai, Emanuele

AU - Brickman, Adam M.

AU - Callahan, Brandy L.

AU - Corriveau, Roderick A.

AU - Fossati, Silvia

AU - Gottesman, Rebecca F.

AU - Gustafson, Deborah R.

AU - Hachinski, Vladimir

AU - Hayden, Kathleen M.

AU - Helman, Alex M.

AU - Hughes, Timothy M.

AU - Isaacs, Jeremy D.

AU - Jefferson, Angela L.

AU - Johnson, Sterling C.

AU - Kapasi, Alifiya

AU - Kern, Silke

AU - Kwon, Jay C.

AU - Kukolja, Juraj

AU - Lee, Athene

AU - Lockhart, Samuel N.

AU - Murray, Anne

AU - Osborn, Katie E.

AU - Power, Melinda C.

AU - Price, Brittani R.

AU - Rhodius-Meester, Hanneke F.M.

AU - Rondeau, Jacqueline A.

AU - Rosen, Allyson C.

AU - Rosene, Douglas L.

AU - Schneider, Julie A.

AU - Scholtzova, Henrieta

AU - Shaaban, C. Elizabeth

AU - Silva, Narlon C.B.S.

AU - Snyder, Heather M.

AU - Swardfager, Walter

AU - Troen, Aron M.

AU - van Veluw, Susanne J.

AU - Vemuri, Prashanthi

AU - Wallin, Anders

AU - Wellington, Cheryl

AU - Wilcock, Donna M.

AU - Xie, Sharon Xiangwen

AU - Hainsworth, Atticus H.

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

KW - Leukoaraiosis

KW - Small vessel disease

KW - Vascular cognitive impairment

KW - Vascular dementia

KW - White matter lesions

UR - https://www.scopus.com/pages/publications/85063999193

UR - https://www.scopus.com/pages/publications/85063999193#tab=citedBy

U2 - 10.1016/j.trci.2019.02.001

DO - 10.1016/j.trci.2019.02.001

M3 - Short survey

AN - SCOPUS:85063999193

VL - 5

SP - 107

EP - 117

JO - Alzheimer's and Dementia: Translational Research and Clinical Interventions

JF - Alzheimer's and Dementia: Translational Research and Clinical Interventions

ER -

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

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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Cite this