White matter hyperintensities across the adult lifespan: Relation to age, Aβ load, and cognition
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BACKGROUND: White matter hyperintensities (WMH) are very frequent in older adults and associated with worse cognitive performance. Little is known about the links between WMH and vascular risk factors, cortical β-amyloid (Aβ) load, and cognition in cognitively unimpaired adults across the entire lifespan, especially in young and middle-aged adults. METHODS: One hundred and thirty-seven cognitively unimpaired adults from the community were enrolled (IMAP cohort). Participants underwent (i) a comprehensive neuropsychological assessment of episodic memory, processing speed, working memory, and executive functions; (ii) brain structural T1 and FLAIR MRI scans used for the automatic segmentation of total and regional (frontal, parietal, temporal, occipital, and corpus callosum) WMH; and (iii) a Florbetapir-PET scan to measure cortical Aβ. The relationships of total and regional WMH to age, vascular risk factors, cortical Aβ, and cognition were assessed within the whole sample, but also splitting the sample in two age groups (≤ or > 60 years old). RESULTS: WMH increased with age across the adult lifespan, i.e., even in young and middle-aged adults. Systolic blood pressure, diastolic blood pressure, and glycated hemoglobin were all associated with higher WMH before, but not after, adjusting for age and the other vascular risk factors. Higher frontal, temporal, and occipital WMH were associated with greater Aβ, but this association was no longer significant when adjusting for age and vascular risk factors. Higher total and frontal WMH were associated with worse performance in executive functions, with no interactive effect of the age group. In contrast, there was a significant interaction of the age group on the link between WMH and working memory, which was significant within the subgroup of young/middle-aged adults only. Adding cortical Aβ load in the models did not alter the results, and there was no interaction between WMH and Aβ on cognition. CONCLUSION: WMH increased with age and were associated with worse executive functions across the adult lifespan and with worse working memory in young/middle-aged adults. Aβ load was weakly associated with WMH and did not change the relationship found between WMH and executive functions. This study argues for the clinical relevance of WMH across the adult lifespan, even in young and middle-aged adults with low WMH.
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WMHs in all cortical regions (frontal, occipital, parietal and temporal) are associated with deficits in executive function scores.
“Previous studies investigating the impact of regional distribution of WMHs on executive function (EF) found that WMHs in all cortical regions (frontal areas, occipital, parietal and temporal) are associated with deficits in EF scores [15,16,17]”
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 [16]
The Results section (“Associations between WMH and cognition”; page unavailable) links frontal WMH to worse executive-function performance. Parietal and occipital associations did not survive correction for multiple comparisons, and Table 4 shows no significant temporal association. The claim therefore overstates the evidence by saying the association holds in all four regions. (LLM, conf=0.92)
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White matter hyperintensity load is associated with premature brain aging
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White Matter Hyperintensity as a Vascular Contribution to the AT(N) Framework
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- Authors
- Garnier-Crussard, A., Bougacha, S., Wirth, M., André, C., Delarue, M., Landeau, B., Mézenge, F., Kuhn, E., Gonneaud, J., Chocat, A., Quillard, A., Ferrand-Devouge, E., de La Sayette, V., Vivien, D., Krolak-Salmon, P., & Chételat, G.
- Affiliations
- Inserm (FR)
- German Center for Neurodegenerative Diseases (DZNE) Dresden (DE)
- Corresponding author
- Chételat, Gaël
- ORCID
- Venue
- Alzheimer's Research & Therapy
- Published
- 2020-10-08
- Volume
- 12
- Issue
- 1
- Pages
- 127-127
- ISSN
- 1758-9193 (ISSN-L)
- PMC
- PMC7545576
- OpenAlex
- W3092538613
- Cited by
- 130
- References
- 54
- Citations by year
- 2026: 18 · 2025: 33 · 2024: 22 · 2023: 25 · 2022: 20 · 2021: 12
- FWCI
- 6.17
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Alzheimer s Research & Therapy (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DZNE Pub (submittedVersion, other-oa)
- Funders
- Institut National de la Santé et de la Recherche Medicale
- Programme Hospitalier de Recherche Clinique (PHRCN 2011-A01493-38, 2012 12-006-0347)
- Agence Nationale de la Recherche
- Fondation Plan Alzheimer
- Fondation LECMA-Vaincre Alzheimer (13732)
- Association France Alzheimer et maladies apparentées, the Région Basse-Normandie
- Agence régionale de santé Auvergne-Rhône-Alpes
- Horizon 2020 (667696)
- 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, vascular risk factors, aging, executive function, working memory, episodic memory, processing speed, young and middle-aged adults, systolic blood pressure, HbA1c, cognitive aging
- MeSH terms
- Aged, Brain, Cognition, Humans, Longevity, Magnetic Resonance Imaging, Middle Aged, Neuropsychological Tests, 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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