Strategic white matter hyperintensity locations for cognitive impairment: A multicenter lesion-symptom mapping study in 3525 memory clinic patients
Alzheimer's Disease Neuroimaging Initiative
(2023) Alzheimer's & Dementia, volume 19, issue 6, pp. 2420 - 2432
(Article)
Abstract
INTRODUCTION: Impact of white matter hyperintensities (WMH) on cognition likely depends on lesion location, but a comprehensive map of strategic locations is lacking. We aimed to identify these locations in a large multicenter study. METHODS: Individual patient data (n = 3525) from 11 memory clinic cohorts were harmonized. We determined
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the association of WMH location with attention and executive functioning, information processing speed, language, and verbal memory performance using voxel-based and region of interest tract-based analyses. RESULTS: WMH in the left and right anterior thalamic radiation, forceps major, and left inferior fronto-occipital fasciculus were significantly related to domain-specific impairment, independent of total WMH volume and atrophy. A strategic WMH score based on these tracts inversely correlated with performance in all domains. DISCUSSION: The data show that the impact of WMH on cognition is location-dependent, primarily involving four strategic white matter tracts. Evaluation of WMH location may support diagnosing vascular cognitive impairment. HIGHLIGHTS: We analyzed white matter hyperintensities (WMH) in 3525 memory clinic patients from 11 cohorts The impact of WMH on cognition depends on location We identified four strategic white matter tracts A single strategic WMH score was derived from these four strategic tracts The strategic WMH score was an independent determinant of four cognitive domains.
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Keywords: cognitive impairment, lesion symptom mapping, location, memory clinic patients, white matter hyperintensities, Clinical Neurology, Geriatrics and Gerontology, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Health Policy, Developmental Neuroscience, Epidemiology, Journal Article
ISSN: 1552-5260
Publisher: John Wiley & Sons Inc.
Note: Funding Information: We are grateful to the diverse participants who contribute to our research. The Meta VCI Map consortium is supported by Vici Grant 918.16.616 from ZonMw to G.J.B. This study was supported by Off Road grant (project 04510011910032) from ZonMW to J.M.B. and a Rudolf Magnus Young Talent Fellowship from the UMC Utrecht Brain Center to J.M.B. C.D.C., E.F.F., and P.M.M. were supported by NIA P30 AG10129, P30 AG072972 and U01 AG024904. ADNI 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 ( www.fnih.org ). 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. A.C.E. was funded by Alzheimer Nederland. PRODEM was supported by the Austrian Science Fund (FWF grants KLI523, P30134, and I2889‐B31). The YOAD study was funded by Alzheimer's Research UK (ARUK‐Network 2012‐6‐ICE). Funding Information: F.B. is supported by the NIHR biomedical research center at UCLH. M.D. received honoraria for lectures from Bayer Vital and Sanofi Genzyme, Consultant for Hovid Berhad and Roche Pharma. R.W.P. received honoraria from GE Healthcare and is co‐lead of Neurofilament light consortium. C.H.S. is supported by an Alzheimer's Society Fellowship. The remaining authors have nothing to disclose. Author disclosures are available in the supporting information . Funding Information: We are grateful to the diverse participants who contribute to our research. The Meta VCI Map consortium is supported by Vici Grant 918.16.616 from ZonMw to G.J.B. This study was supported by Off Road grant (project 04510011910032) from ZonMW to J.M.B. and a Rudolf Magnus Young Talent Fellowship from the UMC Utrecht Brain Center to J.M.B. C.D.C., E.F.F., and P.M.M. were supported by NIA P30 AG10129, P30 AG072972 and U01 AG024904. ADNI 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 (www.fnih.org). 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. A.C.E. was funded by Alzheimer Nederland. PRODEM was supported by the Austrian Science Fund (FWF grants KLI523, P30134, and I2889-B31). The YOAD study was funded by Alzheimer's Research UK (ARUK-Network 2012-6-ICE). Publisher Copyright: © 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
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