Amyloid pathology and vascular risk are associated with distinct patterns of cerebral white matter hyperintensities: A multicenter study in 3132 memory clinic patients
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INTRODUCTION: White matter hyperintensities (WMH) are associated with key dementia etiologies, in particular arteriolosclerosis and amyloid pathology. We aimed to identify WMH locations associated with vascular risk or cerebral amyloid‐β 1‐42 (Aβ42)‐positive status. METHODS: Individual patient data ( n = 3,132; mean age 71.5 ± 9 years; 49.3% female) from 11 memory clinic cohorts were harmonized. WMH volumes in 28 regions were related to a vascular risk compound score (VRCS) and Aß42 status (based on cerebrospinal fluid or amyloid positron emission tomography), correcting for age, sex, study site, and total WMH volume. RESULTS: VRCS was associated with WMH in anterior/superior corona radiata (B = 0.034/0.038, p < 0.001), external capsule (B = 0.052, p < 0.001), and middle cerebellar peduncle (B = 0.067, p < 0.001), and Aß42‐positive status with WMH in posterior thalamic radiation (B = 0.097, p < 0.001) and splenium (B = 0.103, p < 0.001). DISCUSSION: Vascular risk factors and Aß42 pathology have distinct signature WMH patterns. This regional vulnerability may incite future studies into how arteriolosclerosis and Aß42 pathology affect the brain's white matter. Highlights: Key dementia etiologies may be associated with specific patterns of white matter hyperintensities (WMH). We related WMH locations to vascular risk and cerebral Aβ42 status in 11 memory clinic cohorts. Aβ42 positive status was associated with posterior WMH in splenium and posterior thalamic radiation. Vascular risk was associated with anterior and infratentorial WMH. Amyloid pathology and vascular risk have distinct signature WMH patterns.
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Amyloid pathology and vascular risks are associated with distinct patterns of WMH.
“Biesbroek et al. reported that amyloid pathology and vascular risks were associated with distinct patterns of WMH. 48”
From White matter hyperintensity modulates the amyloid‐tau‐cognition association and anti‐amyloid treatment efficacy in asymptomatic older adults (2025) · cites this paper as [48]
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“Author disclosures are available in the Supporting Information.”
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Regional growth rates of white matter hyperintensities are associated with beta-amyloid burden
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Motoric Cognitive Risk Syndrome and Risk of Cardiovascular Disease: A Population-Based Study
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White matter hyperintensity regression: Fact or artifact?
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- Authors
- Biesbroek, J. M., Coenen, M., DeCarli, C., Fletcher, E. M., Maillard, P. M., Initiative, A. D. N., Barkhof, F., Barnes, J., Benke, T., Chen, C. P. L. H., Dal‐Bianco, P., Dewenter, A., Duering, M., Enzinger, C., Ewers, M., Exalto, L. G., Franzmeier, N., Hilal, S., Hofer, E., Koek, H. L., Maier, A. B., McCreary, C. R., Papma, J. M., Paterson, R. W., Pijnenburg, Y. A. L., Rubinski, A., Schmidt, R., Schott, J. M., Slattery, C. F., Smith, E. E., Sudre, C. H., Steketee, R. M. E., Teunissen, C. E., van den Berg, E., van der Flier, W. M., Venketasubramanian, N., Venkatraghavan, V., Vernooij, M. W., Wolters, F. J., Xin, X., Kuijf, H. J., & Biessels, G. J.
- Affiliations
- University Medical Center Utrecht (NL)
- University of California, Davis (US)
- Amsterdam University Medical Centers (NL)
- Innsbruck Medical University (AT)
- National University of Singapore (SG)
- LMU Klinikum (DE)
- University of Basel (CH)
- Medical University of Graz (AT)
- University of Calgary (CA)
- Erasmus MC (NL)
- Amsterdam Neuroscience (NL)
- UCL Queen Square Institute of Neurology (GB)
- Alzheimer Center Erasmus MC Erasmus MC University Medical Center Rotterdam The Netherlands
- Alzheimer Center Amsterdam Department of Neurology Amsterdam Neuroscience Vrije Universiteit Amsterdam Amsterdam UMC Amsterdam The Netherlands
- Department of Pharmacology Yong Loo Lin School of Medicine National University of Singapore Singapore Singapore
- Corresponding author
- Biesbroek, J. Matthijs
- ORCID
- Biesbroek, J. Matthijs
- Coenen, Mirthe
- DeCarli, Charles
- Fletcher, Evan M.
- Maillard, Pauline M.
- Barkhof, Frederik
- Barnes, Josephine
- Benke, Thomas
- Chen, Christopher P. L. H.
- Dewenter, Anna
- Duering, Marco
- Enzinger, Christian
- Ewers, Michael
- Exalto, Lieza G.
- Franzmeier, Nicolai
- Hilal, Saima
- Hofer, Edith
- Koek, Huiberdina L.
- Maier, Andrea B.
- McCreary, Cheryl R.
- Papma, Janne M.
- Paterson, Ross W.
- Pijnenburg, Yolande A. L.
- Rubinski, Anna
- Schmidt, Reinhold
- Schott, Jonathan M.
- Smith, Eric E.
- Sudre, Carole H.
- Steketee, Rebecca M. E.
- Teunissen, Charlotte E.
- Venketasubramanian, Narayanaswamy
- Venkatraghavan, Vikram
- Vernooij, Meike W.
- Wolters, Frank J.
- Kuijf, Hugo J.
- Biessels, Geert Jan
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2024-03-13
- Volume
- 20
- Issue
- 4
- Pages
- 2980-2989
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- PMC
- PMC11032573
- OpenAlex
- W4392761707
- Cited by
- 38
- References
- 59
- Citations by year
- 2026: 12 · 2025: 21 · 2024: 5
- FWCI
- 10.17
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Alzheimer s & Dementia (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, cc-by)
- VU Research Portal (publishedVersion, cc-by)
- UCL Discovery (University College London) (submittedVersion, cc-by)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- Funders
- Alzheimer's Disease Neuroimaging Initiative
- National Institutes of Health (U01 AG024904)
- U.S. Department of Defense (W81XWH‐12‐2‐0012)
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- AbbVie
- Alzheimer's Association
- Alzheimer's Drug Discovery Foundation
- BioClinica
- Biogen
- Bristol-Myers Squibb
- Eli Lilly and Company
- Alzheimer Nederland
- Austrian Science Fund (KLI523, P30134, I2889‐B31)
- Topics
- Health Sciences › Medicine › Neurology › Cerebrovascular and genetic disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- white matter hyperintensities, amyloid-beta 42
- MeSH terms
- Aged, Aged, 80 and over, Dementia, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Amyloid beta-Peptides, Arteriolosclerosis, 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.
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