Journal Article
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; 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
GeroScience · Vol. 47, Issue 1 · pp. 1093-1104 · 2024
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.