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

被引:1
作者
van Setten, Arne [1 ]
Uleman, Jeroen F. [2 ]
Melis, Rene J. F. [1 ]
Lawlor, Brian [3 ]
Riksen, Niels P. [4 ]
Claassen, Jurgen A. H. R. [1 ,5 ]
de Heus, Rianne A. A. [1 ,6 ]
机构
[1] Radboud Univ Nijmegen Med Ctr, Radboudumc Alzheimer Ctr, Dept Geriatr Med, Nijmegen, Netherlands
[2] Univ Copenhagen, Copenhagen Hlth Complex Ctr, Dept Publ Hlth, Oster Farimagsgade 5, DK-1353 Copenhagen, Denmark
[3] Trinity Coll Dublin, Global Brain Hlth Inst, Dublin, Ireland
[4] Radboud Univ Nijmegen Med Ctr, Dept Internal Med, Nijmegen, Netherlands
[5] Univ Leicester, Dept Cardiovasc Sci, Leicester, England
[6] Radboud Univ Nijmegen Med Ctr, Dept Primary & Community Care, Nijmegen, Netherlands
关键词
Alzheimer's disease; ADAS-cog; Progression; Systemic inflammation; Cytokine; Endothelial dysfunction; Biomarker; Mixed model; Longitudinal; Mediation; MITOCHONDRIAL DYSFUNCTION; ADHESION MOLECULE-1; OLDER SUBJECTS; E-SELECTIN; TNF-ALPHA; PLASMA; INFILTRATION; LYMPHOCYTES; IMPAIRMENT; DEMENTIA;
D O I
10.1007/s11357-024-01294-x
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
IntroductionSystemic inflammation and endothelial dysfunction are potentially modifiable factors implicated in Alzheimer's disease (AD), which offer potential therapeutic targets to slow disease progression.MethodsWe investigated the relationship between baseline circulating levels of inflammatory (TNF-alpha, IL-1 ss) 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.ResultsThe 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.DiscussionOur results do not support the role of systemic inflammation or endothelial dysfunction in progression in persons with AD.
引用
收藏
页码:1093 / 1104
页数:12
相关论文
共 74 条
[21]   Computational model of brain endothelial cell signaling pathways predicts therapeutic targets for cerebral pathologies [J].
Gorick, Catherine M. ;
Saucerman, Jeffrey J. ;
Price, Richard J. .
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 2022, 164 :17-28
[22]   MyD88 signaling in brain endothelial cells is essential for the neuronal activity and glucocorticoid release during systemic inflammation [J].
Gosselin, D. ;
Rivest, S. .
MOLECULAR PSYCHIATRY, 2008, 13 (05) :480-497
[23]   The Association Between Circulating Inflammatory Markers and the Progression of Alzheimer Disease in Norwegian Memory Clinic Patients With Mild Cognitive Impairment or Dementia [J].
Hazen, Josje ;
Vistnes, Maria ;
Barca, Maria L. ;
Eldholm, Rannveig S. ;
Persson, Karin ;
Braekhus, Anne ;
Saltvedt, Ingvild ;
Selbaek, Geir ;
Engedal, Knut ;
Knapskog, Anne-Brita .
ALZHEIMER DISEASE & ASSOCIATED DISORDERS, 2020, 34 (01) :47-53
[24]   Systemic inflammation and disease progression in Alzheimer disease [J].
Holmes, C. ;
Cunningham, C. ;
Zotova, E. ;
Woolford, J. ;
Dean, C. ;
Kerr, S. ;
Culliford, D. ;
Perry, V. H. .
NEUROLOGY, 2009, 73 (10) :768-774
[25]   Clinical significance of circulating vascular cell adhesion molecule-1 to white matter disintegrity in Alzheimer's dementia [J].
Huang, Chi-Wei ;
Tsai, Meng-Han ;
Chen, Nai-Ching ;
Chen, Wei-Hsi ;
Lu, Yan-Ting ;
Lui, Chun-Chung ;
Chang, Ya-Ting ;
Chang, Wen-Neng ;
Chang, Alice Y. W. ;
Chang, Chiung-Chih .
THROMBOSIS AND HAEMOSTASIS, 2015, 114 (06) :1230-1240
[26]   Peripheral inflammation and blood-brain barrier disruption: effects and mechanisms [J].
Huang, Xiaowen ;
Hussain, Basharat ;
Chang, Junlei .
CNS NEUROSCIENCE & THERAPEUTICS, 2021, 27 (01) :36-47
[27]   Association between Endothelial Dysfunction and Acute Brain Dysfunction during Critical Illness [J].
Hughes, Christopher G. ;
Morandi, Alessandro ;
Girard, Timothy D. ;
Riedel, Bernhard ;
Thompson, Jennifer L. ;
Shintani, Ayumi K. ;
Pun, Brenda T. ;
Ely, E. Wesley ;
Pandharipande, Pratik P. .
ANESTHESIOLOGY, 2013, 118 (03) :631-639
[28]  
Idriss HT, 2000, MICROSC RES TECHNIQ, V50, P184, DOI 10.1002/1097-0029(20000801)50:3<184::AID-JEMT2>3.0.CO
[29]  
2-H
[30]   NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease [J].
Jack, Clifford R., Jr. ;
Bennett, David A. ;
Blennow, Kaj ;
Carrillo, Maria C. ;
Dunn, Billy ;
Haeberlein, Samantha Budd ;
Holtzman, David M. ;
Jagust, William ;
Jessen, Frank ;
Karlawish, Jason ;
Liu, Enchi ;
Luis Molinuevo, Jose ;
Montine, Thomas ;
Phelps, Creighton ;
Rankin, Katherine P. ;
Rowe, Christopher C. ;
Scheltens, Philip ;
Siemers, Eric ;
Snyder, Heather M. ;
Sperling, Reisa ;
Elliott, Cerise ;
Masliah, Eliezer ;
Ryan, Laurie ;
Silverberg, Nina .
ALZHEIMERS & DEMENTIA, 2018, 14 (04) :535-562