Amyloid pathology and vascular risk are associated with distinct patterns of cerebral white matter hyperintensities: A multicenter study in 3132 memory clinic patients

J. Matthijs Biesbroek*, Mirthe Coenen, for the Alzheimer's Disease Neuroimaging Initiative, Charles DeCarli, Evan M. Fletcher, Pauline M. Maillard, Frederik Barkhof, Josephine Barnes, Thomas Benke, Christopher P.L.H. Chen, Peter Dal-Bianco, Anna Dewenter, Marco Duering, Christian Enzinger, Michael Ewers, Lieza G. Exalto, Nicolai Franzmeier, Saima Hilal, Edith Hofer, Huiberdina L. KoekAndrea B. Maier, Cheryl R. McCreary, Janne M. Papma, Ross W. Paterson, Yolande A.L. Pijnenburg, Anna Rubinski, Reinhold Schmidt, Jonathan M. Schott, Catherine F. Slattery, Eric E. Smith, Carole H. Sudre, Rebecca M.E. Steketee, Charlotte E. Teunissen, Esther van den Berg, Wiesje M. van der Flier, Narayanaswamy Venketasubramanian, Vikram Venkatraghavan, Meike W. Vernooij, Frank J. Wolters, Xu Xin, Hugo J. Kuijf, Geert Jan Biessels

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review



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-β1-42 (Aβ42)-positive status. 


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.


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). 


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.

Original languageEnglish
Pages (from-to)2980-2989
Number of pages10
JournalAlzheimer's and Dementia
Issue number4
Publication statusPublished - Apr 2024

Bibliographical note

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© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.


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