Blood-brain barrier water exchange in relation to amyloid, cognition and cerebrovascular burden

Blood-brain barrier (BBB) water exchange may serve as a sensitive early biomarker for Alzheimer's disease and age-related cognitive decline. This study applied a non-invasive multi-echo arterial spin labeling (ASL) technique to measure BBB water exchange time (Tex), cerebral blood flow (CBF), and arterial transit time (ATT) in 160 adults aged 50 years and older. Participants were classified as cognitively normal (CN), having subjective cognitive decline (SCD), or mild cognitive impairment (MCI). They were assessed for amyloid status and cerebrovascular burden. Compared to CN participants, Tex was significantly lower in both SCD (-9.5 %) and MCI (-14.5 %) groups, suggesting that reductions in BBB water exchange emerge early in the course of cognitive decline. In contrast, CBF was reduced only in MCI participants (-20.8 % compared to CN), and ATT was significantly increased only in individuals with severe cerebrovascular burden (Fazekas score 3). Notably, Tex showed a stepwise decrease with increasing Fazekas scores (1-2), supporting its sensitivity to moderate small vessel disease. No associations were found between Tex and amyloid positivity after adjusting for age and sex. These findings indicate that Tex alterations may precede changes in traditional perfusion markers and are more closely related to vascular and early cognitive changes than to amyloid pathology. BBB water exchange mapping may therefore provide a promising, non-invasive tool to detect early neurovascular dysfunction that contributes to cognitive decline in aging populations, potentially offering a useful biomarker for early intervention trials targeting vascular contributions to dementia.

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Publication Details

Journal
NeuroImage Clinical
Published
2025-12-11
DOI
https://doi.org/10.1016/j.nicl.2025.103926
Primary Topic
Dementia and Cognitive Impairment Research
Type
article
Field-Weighted Citation Impact
0.00

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article

Blood-brain barrier water exchange in relation to amyloid, cognition and cerebrovascular burden

Markus H. Sneve, Lene Pålhaugen, Anders M. Fjell, Klaus Eickel et al.
NeuroImage Clinical
Dementia and Cognitive Impairment Research
article

Blood-brain barrier water exchange in relation to amyloid, cognition and cerebrovascular burden

Markus H. Sneve, Lene Pålhaugen, Anders M. Fjell, Klaus Eickel, Mario Tranfa, Oliver Marcel Geier, Bjørn‐Eivind Kirsebom, Henk J. M. M. Mutsaerts, Sandra Tecelão, Amnah Mahroo, Kristine B. Walhovd, Atle Bjørnerud, Frederik Barkhof, Tormod Fladby, Jan Petr, Federico Masserini, Beatriz Padrela, David Lee Thomas, Per Selnes, Maksim Slivka, Matthias Günther, E. FALCH
article en

Abstract

Blood-brain barrier (BBB) water exchange may serve as a sensitive early biomarker for Alzheimer's disease and age-related cognitive decline. This study applied a non-invasive multi-echo arterial spin labeling (ASL) technique to measure BBB water exchange time (Tex), cerebral blood flow (CBF), and arterial transit time (ATT) in 160 adults aged 50 years and older. Participants were classified as cognitively normal (CN), having subjective cognitive decline (SCD), or mild cognitive impairment (MCI). They were assessed for amyloid status and cerebrovascular burden. Compared to CN participants, Tex was significantly lower in both SCD (-9.5 %) and MCI (-14.5 %) groups, suggesting that reductions in BBB water exchange emerge early in the course of cognitive decline. In contrast, CBF was reduced only in MCI participants (-20.8 % compared to CN), and ATT was significantly increased only in individuals with severe cerebrovascular burden (Fazekas score 3). Notably, Tex showed a stepwise decrease with increasing Fazekas scores (1-2), supporting its sensitivity to moderate small vessel disease. No associations were found between Tex and amyloid positivity after adjusting for age and sex. These findings indicate that Tex alterations may precede changes in traditional perfusion markers and are more closely related to vascular and early cognitive changes than to amyloid pathology. BBB water exchange mapping may therefore provide a promising, non-invasive tool to detect early neurovascular dysfunction that contributes to cognitive decline in aging populations, potentially offering a useful biomarker for early intervention trials targeting vascular contributions to dementia.

NeuroImage ClinicalVol. 49
Oslo University Hospital (NO), University Hospital of North Norway (NO), University of Oslo (NO), Akershus University Hospital (NO), Helmholtz-Zentrum Dresden-Rossendorf (DE), Hochschule Bremerhaven (DE), Amsterdam Neuroscience (NL), Fraunhofer Institute for Wind Energy Systems (DE), Fraunhofer Institute for Digital Medicine (DE), National Hospital for Neurology and Neurosurgery (GB), University College London (GB)
Eli Lilly and Company, Biogen, EU Joint Programme – Neurodegenerative Disease Research, Rijksdienst voor Ondernemend Nederland, Prothena, Celltrion, National Institute for Health and Care Research, European Commission, ZonMw, Bundesministerium für Bildung und Forschung, Eisai, Norges Forskningsråd, University College London Hospitals NHS Foundation Trust, Alzheimer Nederland, Eurostars
Openalex Percentile: Top 53%
Dementia and Cognitive Impairment Research
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