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February 22, 2012

Circulating IL-6 and CRP are associated with MRI findings in the elderly
The 3C-Dijon Study

March 6, 2012 issue
78 (10) 720-727

Abstract

Objective:

The relation between inflammation and brain MRI findings in the elderly remains poorly known. We investigated the association of circulating interleukin-6 (IL-6) and C-reactive protein (CRP) levels with baseline and longitudinal white matter hyperintensities (WMH), silent brain infarction, and brain volumes in community-dwelling elderly free of dementia.

Methods:

We included 1,841 participants aged 65 to 80 years from the Three City-Dijon cohort. Participants followed an MRI examination at baseline and after a 4-year follow-up (n = 1,316). IL-6 and CRP concentrations were measured at baseline from fasting blood samples. WMH were detected with an automatic imaging processing method and gray matter, hippocampal, white matter, and CSF volumes were estimated with voxel-based morphometry. Silent brain infarctions were assessed visually and defined as focal lesions of ≥3 mm in the absence of stroke. We used analysis of covariance and logistic regression to model the associations between inflammatory biomarkers and brain MRI findings adjusting for potential confounders.

Results:

In cross-sectional analyses, higher IL-6 levels were associated with higher WMH volumes (p < 0.01), lower gray matter (p = 0.001) and hippocampal (p = 0.01) volumes, and increasing CSF volumes (p = 0.002) in a dose-relationship pattern. Similar but weaker relations were observed for CRP. We observed no associations between baseline inflammatory biomarker levels and the evolution of MRI findings over 4 years.

Conclusions:

IL-6, and, to a lesser degree, CRP levels were associated with WMH severity as well as global markers of brain atrophy. These results suggest that an inflammatory process may be involved in both age-associated brain alterations.

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Supplementary Material

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STUDY FUNDING

The 3C Study is conducted under a partnership agreement among the Institut National de la Santé et de la Recherche Médicale (INSERM), the Victor Segalen-Bordeaux II University, and Sanofi-Aventis. The Fondation pour la Recherche Médicale funded the preparation and initiation of the study. The 3C Study is also supported by the Caisse Nationale Maladie des Travailleurs Salariés, Direction Générale de la Santé, MGEN, Institut de la Longévité, Conseils Régionaux of Aquitaine and Bourgogne, Fondation de France, Ministry of Research–INSERM Programme “Cohortes et collections de donneés biologiques,” and the Fondation Plan Alzheimer.

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Information & Authors

Information

Published In

Neurology®
Volume 78Number 10March 6, 2012
Pages: 720-727
PubMed: 22357713

Publication History

Received: May 18, 2011
Accepted: October 18, 2011
Published online: February 22, 2012
Published in print: March 6, 2012

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Disclosure

C.L. Satizabal reports no disclosures. Dr. Zhu is funded by the French Chinese Foundation for Science and Applications (FFCSA), the China Scholarship Council (CSC), and the Association de Recherche en Neurologie Vasculaire (ARNEVA). Dr. Mazoyer reports no disclosures. Dr. Dufouil serves as an Associate Editor for the Journal of Alzheimer's Disease and serves as a consultant for Eisai Inc. Dr. Tzourio serves on scientific advisory boards for Merck Sharp & Dohme and Fondation Plan Alzheimer; has received speaker honoraria from Abbott; serves on the editorial boards of Neuroepidemiology and the Journal of Hypertension; and receives research support from Agence Nationale de la Recherche and Fondation Plan Alzheimer.

Authors

Affiliations & Disclosures

C.L. Satizabal, MSc
From the INSERM U708 “Neuroepidemiology” (C.L.S., C.D., C.T.), Bordeaux; Université Pierre et Marie Curie Paris 6 (C.L.S.), Paris; Université Victor Segalen Bordeaux 2 (C.D., C.T.), Bordeaux, France; Department of Neurology (Y.C.Z.), Peking Union Medical College Hospital, Beijing, China; CNRS-CEA UMR 5296 (B.M.), Groupe d'Imagerie Neurofonctionnelle, Bordeaux; Université de Caen Basse-Normandie (B.M.), CHU de Caen (B.M.), Caen; and Institut Universitaire de France (B.M.), Paris, France.
Y.C. Zhu, MD, PhD
From the INSERM U708 “Neuroepidemiology” (C.L.S., C.D., C.T.), Bordeaux; Université Pierre et Marie Curie Paris 6 (C.L.S.), Paris; Université Victor Segalen Bordeaux 2 (C.D., C.T.), Bordeaux, France; Department of Neurology (Y.C.Z.), Peking Union Medical College Hospital, Beijing, China; CNRS-CEA UMR 5296 (B.M.), Groupe d'Imagerie Neurofonctionnelle, Bordeaux; Université de Caen Basse-Normandie (B.M.), CHU de Caen (B.M.), Caen; and Institut Universitaire de France (B.M.), Paris, France.
B. Mazoyer, MD, PhD
From the INSERM U708 “Neuroepidemiology” (C.L.S., C.D., C.T.), Bordeaux; Université Pierre et Marie Curie Paris 6 (C.L.S.), Paris; Université Victor Segalen Bordeaux 2 (C.D., C.T.), Bordeaux, France; Department of Neurology (Y.C.Z.), Peking Union Medical College Hospital, Beijing, China; CNRS-CEA UMR 5296 (B.M.), Groupe d'Imagerie Neurofonctionnelle, Bordeaux; Université de Caen Basse-Normandie (B.M.), CHU de Caen (B.M.), Caen; and Institut Universitaire de France (B.M.), Paris, France.
C. Dufouil, PhD
From the INSERM U708 “Neuroepidemiology” (C.L.S., C.D., C.T.), Bordeaux; Université Pierre et Marie Curie Paris 6 (C.L.S.), Paris; Université Victor Segalen Bordeaux 2 (C.D., C.T.), Bordeaux, France; Department of Neurology (Y.C.Z.), Peking Union Medical College Hospital, Beijing, China; CNRS-CEA UMR 5296 (B.M.), Groupe d'Imagerie Neurofonctionnelle, Bordeaux; Université de Caen Basse-Normandie (B.M.), CHU de Caen (B.M.), Caen; and Institut Universitaire de France (B.M.), Paris, France.
C. Tzourio, MD, PhD
From the INSERM U708 “Neuroepidemiology” (C.L.S., C.D., C.T.), Bordeaux; Université Pierre et Marie Curie Paris 6 (C.L.S.), Paris; Université Victor Segalen Bordeaux 2 (C.D., C.T.), Bordeaux, France; Department of Neurology (Y.C.Z.), Peking Union Medical College Hospital, Beijing, China; CNRS-CEA UMR 5296 (B.M.), Groupe d'Imagerie Neurofonctionnelle, Bordeaux; Université de Caen Basse-Normandie (B.M.), CHU de Caen (B.M.), Caen; and Institut Universitaire de France (B.M.), Paris, France.

Notes

Correspondence & reprint requests to Dr. Tzourio: [email protected]

Author Contributions

C.L. Satizabal performed the statistical analysis and contributed to the interpretation of the data and the drafting of the manuscript for intellectual content. Dr. Zhu performed the assessment of silent brain infarctions in MRI and contributed to revising the manuscript for intellectual content. Dr. Mazoyer contributed to the design and conceptualization of the study. Dr. Dufouil contributed to the design and conceptualization of the study and revising the manuscript for intellectual content. Dr. Tzourio contributed to the design and conceptualization of the study, supervised the analysis of the data and the interpretation of the results, and revised the manuscript for intellectual content.

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