Journal Article

DZNE-2025-01054

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png White matter hyperintensities contribute to early cortical thinning in addition to tau in aging.

Leone, R. (First author)DZNE* ; Kobeleva, X. (Last author)DZNE* ; Initiative, A. D. N. (Collaboration Author)

2025
Elsevier Science Amsterdam [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.neurobiolaging.2025.07.007

Abstract: White matter hyperintensities (WMH) are associated with cortical thinning in distant brain regions. However, it is currently unclear how WMH affect neurodegeneration in early Alzheimer's disease (AD). Here, we investigated associations between WMH and cortical thickness in temporal regions involved in early AD (AD cortical signature), while correcting for regional amyloid and tau accumulation assessed by PET. We performed cross-sectional (n = 551), and longitudinal (n = 125) analyses in older adults without dementia, also stratified by amyloid positivity. We evaluated WMH volume - as a measure of the global burden of WMH-related cerebrovascular pathology (GB-WMH) - and investigated the role of deep versus periventricular WMH. We also tested whether a higher focal burden of WMH in specific tracts connected to AD signature regions (FB-WMH) would lead to greater cortical thinning than expected solely from GB-WMH. We performed exploratory analyses in other brain regions to check the specificity of our findings to the temporal AD signature. GB-WMH damage, especially involving periventricular WMH, was cross-sectionally (not longitudinally) associated with cortical thinning in the fusiform, inferior and middle temporal gyri. Stronger associations were found in amyloid-positive individuals, including for the entorhinal cortex. Effects were mostly confined to regions of the temporal AD signature. FB-WMH did not yield higher cortical thinning than expected solely by GB-WMH. Cerebrovascular disease is associated with cortical thinning of temporal regions involved in early AD. Interventions aimed at improving cerebrovascular health might help to mitigate neurodegeneration in these regions.

Keyword(s): AD ; Alzheimer’s Disease ; Amyloid ; Copathologies ; Cortical thickness ; Disconnections ; Tau ; WMH

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Contributing Institute(s):

1. Clinical Research Coordination (Clinical Research (Bonn))
2. Clinical Research Platform (CRP) (AG Spottke)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2025

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF < 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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