ORIGINAL RESEARCH article
Front. Aging Neurosci.
Sec. Alzheimer's Disease and Related Dementias
Volume 17 - 2025 | doi: 10.3389/fnagi.2025.1595071
This article is part of the Research TopicThe early detection of neurodegenerative diseases: an aging perspectiveView all 7 articles
Associations of plasma von Willebrand Factor levels with cognitive decline and neurodegeneration in older adults without dementia
Provisionally accepted- Taizhou First People's Hospital, Taizhou, China
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Background: Previous studies have suggested that von Willebrand Factor (VWF) may be implicated in the pathogenesis of Alzheimer's disease (AD). However, the association between plasma VWF levels and cognitive decline and neurodegeneration in older adults without dementia remains unclear.We investigated the cross-sectional and longitudinal associations between plasma von Willebrand Factor (VWF) levels and cognitive decline, as measured by the Mini-Mental State Examination (MMSE) and the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB), as well as the volumes of six brain regions: the hippocampus, entorhinal cortex, middle temporal gyrus, fusiform gyrus, ventricles, and whole brain. Linear mixed-effects models were used to assess the association between plasma VWF levels and longitudinal changes in cognitive function and neuroimaging markers over time.The study cohort consisted of 340 older adults without dementia at baseline. We observed that lower plasma VWF levels were associated with a faster rate of cognitive decline (MMSE: coefficient = 0.204, 95% CIs = [0.030, 0.378], p-value = 0.021; CDR-SB: coefficient = -0.268, 95% CIs = [-0.374, -0.163], p-value <0.001). Additionally, lower plasma VWF levels were linked to a more rapid reduction in the volumes of the hippocampus (coefficient = 0.016, 95% CIs = [0.004, 0.027], p-value = 0.009), entorhinal cortex (coefficient = 0.031, 95% CIs = [0.014, 0.048], p-value <0.001), and fusiform gyrus (coefficient = 0.047, 95% CIs = [0.008, 0.085], p-value = 0.017), as well as a faster enlargement of the ventricles (coefficient = -0.380, 95% CIs = [-0.558, -0.203], p-value <0.001). However, no significant relationships were observed between plasma VWF levels and changes in the volumes of the middle temporal gyrus or the whole brain (all p-values > 0.05).Our findings may contribute to the growing body of knowledge on the vascular contributions to cognitive function and may help identify potential biomarkers for the early detection and intervention of AD.
Keywords: Alzheimer's disease, von Willebrand Factor, cognitive decline, structural MRI, brain atrophy
Received: 17 Mar 2025; Accepted: 07 Aug 2025.
Copyright: © 2025 Fu and Hu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Meiling Hu, Taizhou First People's Hospital, Taizhou, China
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