Brain amyloid and vascular risk are related to distinct white matter hyperintensity patterns
Open accessAbstract
White matter hyperintensities (WMHs) are associated with vascular risk and Alzheimer’s disease. In this study, we examined relations between WMH load and distribution, amyloid pathology and vascular risk in 339 controls and cases with either subjective (SCD) or mild cognitive impairment (MCI). Regional deep (DWMH) and periventricular (PWMH) WMH loads were determined using an automated algorithm. We stratified on Aβ1-42 pathology (Aβ+/−) and analyzed group differences, as well as associations with Framingham Risk Score for cardiovascular disease (FRS-CVD) and age. Occipital PWMH ( p = 0.001) and occipital DWMH ( p = 0.003) loads were increased in SCD-Aβ+ compared with Aβ− controls. In MCI-Aβ+ compared with Aβ− controls, there were differences in global WMH ( p = 0.003), as well as occipital DWMH ( p = 0.001) and temporal DWMH ( p = 0.002) loads. FRS-CVD was associated with frontal PWMHs ( p = 0.003) and frontal DWMHs ( p = 0.005), after adjusting for age. There were associations between global and all regional WMH loads and age. In summary, posterior WMH loads were increased in SCD-Aβ+ and MCI-Aβ+ cases, whereas frontal WMHs were associated with vascular risk. The differences in WMH topography support the use of regional WMH load as an early-stage marker of etiology.
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The majority of published studies have emphasized the spatial heterogeneity of WMHs but have left the potential heterogeneous influences of regional Aβ deposition relatively unexplored.
“The majority of published studies have emphasized the spatial heterogeneity of WMHs [25,26], but have left the potential heterogeneous influences of regional Aβ deposition relatively unexplored.”
From Amyloid-PET and White Matter Hyperintensities Have Independent Effects on Baseline Cognitive Function and Synergistic Effects on Longitudinal Executive Function (2023) · cites this paper as [25]
The Introduction and Discussion > Interpretation describe prior studies of regional WMH patterns, and this paper itself examines WMH distribution. They support the citation as an example of work on spatial heterogeneity, but do not establish that a majority of published studies emphasized it. The citation is attached to that first clause, not the subsequent claim about regional Aβ deposition. (LLM, conf=0.78)
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“The majority of published studies have emphasized the spatial heterogeneity of WMHs [25,26], but have left the potential heterogeneous influences of regional Aβ deposition relatively unexplored.”
Background
- Authors
- Pålhaugen, L., Sudre, C. H., Tecelao, S., Nakling, A., Almdahl, I. S., Kalheim, L. F., Cardoso, M. J., Johnsen, S. H., Rongve, A., Aarsland, D., Bjørnerud, A., Selnes, P., & Fladby, T.
- Affiliations
- University of Oslo (NO)
- King's College London (GB)
- Department of Neurology, Akershus University Hospital, Lørenskog, Norway
- Betanien Hospital (NO)
- Oslo University Hospital (NO)
- University Hospital of North Norway (NO)
- University of Bergen (NO)
- Corresponding author
- Pålhaugen, Lene
- ORCID
- Venue
- Journal of Cerebral Blood Flow & Metabolism
- Publisher
- SAGE Publications
- Published
- 2020-09-21
- Volume
- 41
- Issue
- 5
- Pages
- 1162-1174
- ISSN
- 0271-678X (ISSN-L)
- 1559-7016
- PMC
- PMC8054718
- OpenAlex
- W3049646466
- Cited by
- 79
- References
- 52
- Citations by year
- 2026: 9 · 2025: 17 · 2024: 19 · 2023: 22 · 2022: 10 · 2021: 2
- FWCI
- 3.68
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Journal of Cerebral Blood Flow & Metabolism (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- NORA - Norwegian Open Research Archives (submittedVersion, cc-by)
- UCL Discovery (University College London) (submittedVersion)
- NORA - Norwegian Open Research Archives (submittedVersion, other-oa)
- Funders
- Wellcome Trust (203148/Z/16/Z)
- Alzheimer's Society (AS‐JF‐17‐011)
- 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, amyloid-beta 42, vascular risk, cardiovascular risk, mild cognitive impairment, subjective cognitive decline, deep white matter hyperintensities, periventricular white matter hyperintensities, occipital white matter, frontal white matter, Alzheimer's disease, aging
- MeSH terms
- Heart Disease Risk Factors, Adult, Aged, Aged, 80 and over, Algorithms, Alzheimer Disease, Amyloid, Brain, Cerebrospinal Fluid, Female, Frontal Lobe, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Middle Aged, Neuropsychological Tests, Norway, Occipital Lobe, Temporal Lobe, Vascular Diseases, Case-Control Studies, Leukoaraiosis, Cognitive Dysfunction, White Matter
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