White matter hyperintensity topography in Alzheimer's disease and links to cognition
Open accessAbstract
Introduction: White matter hyperintensities (WMH) are often described in Alzheimer's disease (AD), but their topography and specific relationships with cognition remain unclear. Methods: Regional WMH were estimated in 54 cognitively impaired amyloid beta–positive AD (Aβpos‐AD), compared to 40 cognitively unimpaired amyloid beta–negative older controls (Aβneg‐controls) matched for vascular risk factors. The cross‐sectional association between regional WMH volume and cognition was assessed within each group, controlling for cerebral amyloid burden, global cortical atrophy, and hippocampal atrophy. Results: WMH volume was larger in Aβpos‐AD compared to Aβneg‐controls in all regions, with the greatest changes in the splenium of the corpus callosum (S‐CC). In Aβpos‐AD patients, larger total and regional WMH volume, especially in the S‐CC, was strongly associated with decreased cognition. Discussion: WMH specifically contribute to lower cognition in AD, independently from amyloid deposition and atrophy. This study emphasizes the clinical relevance of WMH in AD, especially posterior WMH, and most notably S‐CC WMH.
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The spatial distribution of WMH is differentially associated with amyloid pathology, vascular risks, and specific cognitive domains.
“The spatial distribution of WMH was found to be differentially associated with amyloid pathology, vascular risks, and specific cognitive domains. 18 , 19 , 64”
From White matter hyperintensity modulates the amyloid‐tau‐cognition association and anti‐amyloid treatment efficacy in asymptomatic older adults (2025) · cites this paper as [64]
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White matter hyperintensities in Alzheimer's disease: Beyond vascular contribution
Garnier‐Crussard, A., Cotton, F., Krolak‐Salmon, P., & Chételat, G. (2023) · Alzheimer's & Dementia · doi:10.1002/alz.13057 · Cited by 139 · see citing works
Self-citationMirkin, S., & Albensi, B. C. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2023.1094233 · Cited by 46 · see citing works
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Lin, Z., Hong, Y., Hu, Y., Xiao, Q., Peng, S., Wu, D., Guo, T., & Jiang, D. (2025) · Alzheimer's & Dementia · doi:10.1002/alz.70990 · Cited by 2 · see citing works
- Authors
- Garnier‐Crussard, A., Bougacha, S., Wirth, M., Dautricourt, S., Sherif, S., Landeau, B., Gonneaud, J., De Flores, R., de la Sayette, V., Vivien, D., Krolak‐Salmon, P., & Chételat, G.
- Affiliations
- Inserm (FR)
- German Center for Neurodegenerative Diseases (DZNE) Dresden (DE)
- Normandie Univ UNICAEN INSERM U1237 PhIND “Physiopathology and Imaging of Neurological Disorders,” Institut Blood and Brain @ Caen‐Normandie Cyceron Caen France
- Department of Neurology CHU de Caen Caen France
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Chételat, Gaël
- ORCID
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2021-07-28
- Volume
- 18
- Issue
- 3
- Pages
- 422-433
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- PMC
- PMC9292254
- OpenAlex
- W3183402156
- Cited by
- 170
- References
- 90
- Citations by year
- 2026: 30 · 2025: 39 · 2024: 48 · 2023: 36 · 2022: 16 · 2021: 1
- FWCI
- 18.12
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Alzheimer s & Dementia (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- DZNE Pub (submittedVersion, cc-by-nc)
- Funders
- Agence Nationale de la Recherche (ANR LONGVIE 2007)
- Fondation Plan Alzheimer (2008‐2012)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Neurology › Cerebrovascular and genetic disorders
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- white matter hyperintensities, Alzheimer's disease
- MeSH terms
- Alzheimer Disease, Atrophy, Cognition, Cross-Sectional Studies, Humans, Magnetic Resonance Imaging, Amyloid beta-Peptides, White Matter
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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