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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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).
Alber, Jessica; Alladi, Suvarna; Bae, Hee-Joon; Barton, David A.; Beckett, Laurel A.; Bell, Joanne M.; Berman, Sara E.; Biessels, Geert Jan; Black, Sandra E.; Bos, Isabelle; Bowman, Gene L.; Brai, Emanuele; Brickman, Adam M.; Callahan, Brandy L.; Corriveau, Roderick A.; Fossati, Silvia; Gottesman, Rebecca F.; Gustafson, Deborah R.; Hachinski, Vladimir; Hayden, Kathleen M.; Helman, Alex M.; Hughes, Timothy M.; Isaacs, Jeremy D.; Jefferson, Angela L.; Johnson, Sterling C.; Kapasi, Alifiya; Kern, Silke; Kwon, Jay C.; Kukolja, Juraj; Lee, Athene; Price, Brittani R.; and Wilcock, Donna M., "White Matter Hyperintensities in Vascular Contributions to Cognitive Impairment and Dementia (VCID): Knowledge Gaps and Opportunities" (2019). Sanders-Brown Center on Aging Faculty Publications. 132.