Abstract
Objective This investigation aimed at examining whether circulating inflammatory biomarkers C-reactive protein (CRP), interleukin-6 (IL6), and alpha 1-antichymotrypsin (ACT) were related to cerebrovascular disease (CVD) assessed by MRI.
Methods The study included nondemented elderly participants of a community-based, multiethnic cohort, who received baseline MRI scans and had CRP (n = 508), ACT (435), and IL6 (N = 357) measured by ELISA. Silent brain infarcts and white matter hyperintensities (WMH) were derived from all available MRI scans at baseline, approximately 4.4 years after blood sample collection for inflammatory biomarkers. Repeated assessments of infarcts and WMH, as well as microbleeds assessment, were performed at follow-up MRI visits around 4.5 years later. Cross-sectional and longitudinal relationship between inflammatory biomarkers and CVD were analyzed using appropriate logistic regression models, generalized linear models, or COX models.
Results After adjusting for age, sex, ethnicity, education, APOE genotype, and intracranial volume, 1 SD increase in log10IL6 was associated with infarcts on MRI {odds ratio [OR] (95% confidence interval [CI]) = 1.28 [1.02–1.60], p = 0.033}, and 1 SD increase in log10CRP and log10ACT was associated with microbleeds (OR [95% CI] = 1.46 [1.02–2.09], p = 0.041; and 1.65 [1.11–2.46], p = 0.013; respectively). One SD increase in log10ACT was also associated with larger WMH at the follow-up MRI (b = 0.103, p = 0.012) and increased accumulation of WMH volume (b = 0.062, p = 0.041) during follow-up. The associations remained significant after additional adjustment of vascular risk factors and excluding participants with clinical stroke.
Conclusions Among older adults, increased circulating inflammatory biomarkers were associated with the presence of infarcts and microbleeds, WMH burden, and progression of WMH.
Glossary
- ACT=
- alpha 1-antichymotrypsin;
- APOE=
- apolipoprotein;
- BMI=
- body mass index;
- CAA=
- cerebral amyloid angiopathy;
- CVD=
- cerebrovascular disease;
- CRP=
- C-reactive protein;
- CV=
- coefficient of variation;
- FOV=
- field of view;
- GRE=
- gradient echo;
- ICV=
- intracranial volume;
- IL6=
- interleukin-6;
- WHICAP=
- Washington Heights/Hamilton Heights Inwood Columbia Aging Project;
- WMH=
- white matter hyperintensity;
- sICAM-1=
- intercellular adhesion molecule-1
Footnotes
Funding information and disclosures are provided at the end of the article. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/NN.
The Article Processing Charge was funded by NIH.
- Received March 28, 2018.
- Accepted in final form October 12, 2018.
- Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
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