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. 2025 Feb;47(1):1093-1104.
doi: 10.1007/s11357-024-01294-x. Epub 2024 Jul 31.

No association between markers of systemic inflammation and endothelial dysfunction with Alzheimer's disease progression: a longitudinal study

Arne van Setten #  1 , Jeroen F Uleman #  2 , René J F Melis  1 , Brian Lawlor  3 , Niels P Riksen  4 , Jurgen A H R Claassen  1   5 , Rianne A A de Heus  1   6 ; NILVAD Study Group
Collaborators, Affiliations

No association between markers of systemic inflammation and endothelial dysfunction with Alzheimer's disease progression: a longitudinal study

Arne van Setten et al. Geroscience. 2025 Feb.

Abstract

Introduction: Systemic inflammation and endothelial dysfunction are potentially modifiable factors implicated in Alzheimer's disease (AD), which offer potential therapeutic targets to slow disease progression.

Methods: We investigated the relationship between baseline circulating levels of inflammatory (TNF-α, IL-1ß) and endothelial cell markers (VCAM-1, ICAM-1, E-selectin) and 18-month cognitive decline (ADAS-cog12) in 266 mild-to-moderate AD patients from the NILVAD study. We employed individual growth models to examine associations, potential mediation, and interaction effects while adjusting for confounders.

Results: The average increase in ADAS-cog12 scores over all patients was 8.1 points in 18 months. No significant association was found between the markers and the rate of cognitive decline. Mediation analysis revealed no mediating role for endothelial cell markers, and interaction effects were not observed.

Discussion: Our results do not support the role of systemic inflammation or endothelial dysfunction in progression in persons with AD.

Keywords: ADAS-cog; Alzheimer’s disease; Biomarker; Cytokine; Endothelial dysfunction; Longitudinal; Mediation; Mixed model; Progression; Systemic inflammation.

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Conflict of interest statement

Declarations. Conflict of interest: The authors have no conflict of interest to report.

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