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

Arne van Setten; Jeroen F Uleman; René J F Melis; Brian Lawlor; Niels P Riksen; Jurgen A H R Claassen; Rianne A A de Heus; NILVAD Study Group

doi:10.1007/s11357-024-01294-x

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

Geroscience. 2024 Jul 31. doi: 10.1007/s11357-024-01294-x. Online ahead of print.

Authors

Arne van Setten^#¹, Jeroen F Uleman^#², René J F Melis¹, Brian Lawlor³, Niels P Riksen⁴, Jurgen A H R Claassen^{1

5}, Rianne A A de Heus^{1

6}; NILVAD Study Group

Collaborators

NILVAD Study Group:
Ricardo Segurado, Sean Kennelly, Marcel G M Olde Rikkert, Robert Howard, Florence Pasquier, Anne Börjesson-Hanson, Magda Tsolaki, Ugo Lucca, D William Molloy, Robert Coen, Matthias W Riepe, János Kálmán, Rose Anne Kenny, Fiona Cregg, Sarah O'Dwyer, Cathal Walsh, Jessica Adams, Rita Banzi, Laetitia Breuilh, Leslie Daly, Suzanne Hendrix, Paul Aisen, Siobhan Gaynor, Ali Sheikhi, Diana G Taekema, Frans R Verhey, Raffaello Nemni, Flavio Nobili, Massimo Franceschi, Giovanni Frisoni, Orazio Zanetti, Anastasia Konsta, Orologas Anastasios, Styliani Nenopoulou, Fani Tsolaki-Tagaraki, Magdolna Pakaski, Olivier Dereeper, Vincent de la Sayette, Olivier Sénéchal, Isabelle Lavenu, Agnès Devendeville, Gauthier Calais, Fiona Crawford, Michael Mullan, Maria A Berglund, Jurgen A Claassen, Rianne A de Heus, Daan L K de Jong, Olivier Godefroy, Siobhan Hutchinson, Aikaterini Ioannou, Michael Jonsson, Annette Kent, Jürgen Kern, Petros Nemtsas, Minoa-Kalliopi Panidou, Laila Abdullah, Daniel Paris, Angelina M Santoso, Gerrita J van Spijker, Martha Spiliotou, Georgia Thomoglou, Anders Wallin

Affiliations

¹ Department of Geriatric Medicine, Radboudumc Alzheimer Center, Radboud University Medical Center, Nijmegen, The Netherlands.
² Copenhagen Health Complexity Center, Department of Public Health, University of Copenhagen, Oster Farimagsgade 5, 1353, Copenhagen K, Denmark. [email protected].
³ Global Brain Health Institute, Trinity College, Dublin, Ireland.
⁴ Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
⁵ Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.
⁶ Department of Primary and Community Care, Radboud University Medical Center, Nijmegen, The Netherlands.

^# Contributed equally.

PMID: 39085534
DOI: 10.1007/s11357-024-01294-x

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.

Abstract

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